Dietary calcium but not elemental calcium from supplements is associated with body composition and obesity in Chinese women

Objective

We assessed whether dietary calcium intake or calcium supplements associated with body composition and obesity in a Chinese population.

Methods

A cross-sectional survey was performed in a population of 8940, aged 20 to 74 y. 8127 participants responded (90.9%). Height, weight, fat mass (FM), waist circumference (WC) and hip circumference were measured. Obesity definition: body mass index (BMI) ≥28 kg/m² (overall obesity); WC ≥85 cm for men or ≥80 cm for women (abdominal obesity І) and waist hip ratio (WHR) ≥0.90 for men or ≥0.85 for women (abdominal obesity П). The data on dietary calcium and calcium supplements were collected using food-frequency questionnaire and self-report questionnaire. Multivariate linear and multivariable logistic regressions were used to examine the associations between dietary calcium intake or calcium supplements and body composition and obesity.

Principal Findings

The average dietary calcium intake of all subjects was 430 mg/d. After adjusting for potential confounding factors, among women only, negative associations were observed between habitual dietary calcium intake and four measures of body composition (β, −0.086, P<0.001 for BMI; β, −0.072, P<0.001 for WC; β, −0.044, P<0.05 for WHR; and β, −0.058, P<0.01 for FM, respectively) and both measures of abdominal obesity (Odds Ratio [OR] = 0.86, 95% Confidence Interval [CI], 0.80–0.93; P<0.001, for abdominal obesity I; OR = 0.92, 95% CI, 0.86–0.99; P = 0.026, for abdominal obesity II). These associations were not observed among men (P>0.05). Similarly, among both men and women, we did not observe significant associations between calcium supplements and any measures of body composition or abdominal obesity (P>0.05).

Conclusions

Dietary calcium from food rather than elemental calcium from calcium supplements has beneficial effects on the maintenance of body composition and preventing abdominal obesity in Chinese women.     

Serum cholesterol and the progression of Parkinson's disease: results from DATATOP

Background

Recent studies have suggested that higher serum cholesterol may be associated with lower occurrence of Parkinson''s disease (PD). This study is to test the hypothesis that higher serum cholesterol correlates with slower PD progression.

Methods

Baseline non-fasting serum total cholesterol was measured in 774 of the 800 subjects with early PD enrolled between 1987 and 1988 in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial. Participants were followed for up to two years, with clinical disability requiring levodopa therapy as the primary endpoint. Hazard ratios (HRs) and 95% confidence intervals (CI) were determined for increasing serum cholesterol concentration (in quintiles) for clinical disability requiring levodopa therapy, after adjusting for confounders. At baseline, only nine subjects reported use of cholesterol-lowering agents (two with statins).

Results

The overall mean cholesterol level was 216 mg/dL (range 100–355). The HR of progressing to the primary endpoint decreased with increasing serum cholesterol concentrations. Compared to the lowest quintile, the HRs (95%CI), for each higher quintile (in ascending order) are 0.83 (0.59–1.16); 0.86 (0.61–1.20); 0.84 (0.60–1.18); and 0.75 (0.52–1.09). The HR for one standard deviation (SD) increase = 0.90 [(0.80–1.01), p for trend = 0.09]. This trend was found in males (HR per SD = 0.88 [(0.77–1.00), p for trend = 0.05], but not in females [HR = 1.03 (0.81–1.32)].

Conclusions

This secondary analysis of the DATATOP trial provides preliminary evidence that higher total serum cholesterol concentrations may be associated with a modest slower clinical progression of PD, and this preliminary finding needs confirmation from larger prospective studies.     

The Association of Cysteine with Obesity, Inflammatory Cytokines and Insulin Resistance in Hispanic Children and Adolescents

Context

Plasma total cysteine (tCys) independently relates to fat mass in adults. Dietary cyst(e)ine promotes adiposity and decreases glucose tolerance in some rodent models, but alleviates insulin resistance in others.

Objective

To investigate whether the association of tCys with body fat extends to children at particular risk of obesity, and whether tCys is associated with insulin resistance and obesity-associated inflammation.

Methods

We explored the cross-sectional relations of fasting plasma tCys and related metabolites with body composition measured by dual-energy X-ray absorptiometry in 984 Hispanic children and adolescents aged 4–19 years from the Viva La Familia Study. Linear and logistic regression and dose-response curves were used to evaluate relations of tCys with obesity, insulin resistance and inflammatory markers including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and C-reactive protein (CRP).

Results

tCys, methionine and total homocysteine (tHcy) increased with age. Upper tCys quartile was independently associated with a 5-fold increased risk of obesity (95% CI 3.5–8.0, P<0.001), and 2-fold risk of insulin resistance (95% CI: 1.6-5.0, P<0.001; adjusted for body fat%). Within the overweight/obese subgroup, but not in normal-weight children, tCys accounted for 9% of the variability in body fat% (partial r = 0.30, P<0.001; adjusted for age and gender). tCys correlated positively with serum non-esterified fatty acids and leptin, partly independent of body fat, but was not associated with serum IL-6, TNF-α or MCP-1. A positive correlation with CRP disappeared after adjustment for BMI.

Conclusion

tCys is independently associated with obesity and insulin resistance in Hispanic children and adolescents, highlighting a previously underappreciated link between the sulfur amino acid metabolic pathway and obesity and cardiometabolic risk.     

Association of the European Lactase Persistence Variant (LCT-13910 C>T Polymorphism) with Obesity in the Canary Islands

Background

European lactose tolerance genotype (LCT -13910 C>T, rs4988234) has been positively associated to body mass indexes (BMI) in a meta-analysis of 31,720 individuals of northern and central European descent. A strong association of lactase persistence (LP) with BMI and obesity has also been traced in a Spanish Mediterranean population. The aim of this study was to analyze a potential association of LP compared to lactase non-persistence (LNP) with BMI in inhabitants of the Canary Islands of Spain using Mendelian randomization.

Methods

A representative, randomly sampled population of adults belonging to the Canary Islands Nutrition Survey (ENCA) in Spain, aged 18–75 years (n = 551), was genotyped for the LCT – 13910 C>T polymorphism. Milk consumption was assessed by a validated questionnaire. Anthropometric variables were directly measured. WHO classification of BMI was used.

Results

LP individuals were significantly more obese than LNP subjects (χ² = 10.59; p<0.005). LP showed in a multivariate linear regression analysis showed a positive association of LP with BMI compared to LNP, (β = 0.96; 95% CI: 0.08–1.85, p = 0.033). In a multinomial logistic regression analysis normal range weight LP subjects showed an odds ratio for obesity of 2.41; 95%CI 1.39–418, (p = 0.002) compared to LNP.

Conclusions

The T-13910 of the allele LCT-13910 C>T polymorphism is positively associated with BMI. LP increases significantly the risk to develop obesity in the studied population. The LCT-13910 C>T polymorphism stands proxy for the lifetime exposure pattern, milk intake, that may increase susceptibility to obesity and to obesity related pathologies.     

Associations between Apolipoprotein E Genotype, Diet, Body Mass Index, and Serum Lipids in Lithuanian Adult Population

Background

Apolipoprotein E (APOE) polymorphism is associated with lipid levels. Some studies have reported that blood lipid response to diet or obesity varies depending on APOE genotypes. The aim of this study was to assess the effect of APOE genotypes, the intake of saturated fatty acids (SFA), and obesity on serum lipid levels in Lithuanian adult population.

Methodology/Principal Findings

A cross-sectional health survey was carried out in five municipalities of Lithuania. The random sample was obtained from lists of 25–64 year-old inhabitants registered at primary health care centres. The data from 996 subjects (416 men and 580 women) were analysed in this study. Two single-nucleotide polymorphisms (rs429358 and rs7412) were assessed using a real-time polymerase chain reaction. 24-hour recall and food frequency questionnaire were used for evaluation of dietary habits. Serum lipids were determined using enzymatic methods.Men and women with the APOE2 genotype had the lowest level of total cholesterol (TC) (p = 0.002 for men, and p = 0.02 for women) and low-density lipoprotein cholesterol (LDL-C) (p<0.001). Multivariate linear regression analysis showed that age, genotype APOE2, SFA intake, and body mass index (BMI) were significant determinants of TC and LDL-C level (with p values ranging from 0.043 to 0.001). Our data did not reveal any statistically significant interactions between APOE genotype and SFA intake or between APOE genotype and BMI regarding TC and LDL-C level (all p>0.05). However, the predictive power of the regression model for LDL-C improved when gene-BMI interaction and gene-BMI interaction plus gene-nutrient interaction were added (p = 0.04 and p = 0.032 for R² change, respectively).

Conclusions/Significance

APOE genotypes, SFA intake, and obesity were found to be associated with blood lipid levels in Lithuanian adult population. Analysis of gene-diet and gene-obesity interactions did not confirm that the effects of diet and obesity on TC and LDL-C level significantly depended on APOE genotype.     

Evaluation of the association between the AC3 genetic polymorphisms and obesity in a Chinese Han population

Background

AC3 is one of adenylyl cyclase isoforms involved in cAMP and insulin signaling pathway. Recent reports have demonstrated that the AC3 genetic polymorphisms are associated with obesity in a Swedish population. AC3 knock out mice exhibit obese when they age. These findings suggest that AC3 plays an important role in the regulation of body weight.

Methodology/Principal Findings

In the present study, we evaluated the association between the AC3 genetic polymorphisms and obesity in a Han Chinese population. A total of 2580 adults, including 1490 lean (BMI = 18.5–23.9), 677 overweight (BMI 24.0–27.9) and 413 obese (BMI ≥28.0) subjects were genotyped for 5 TagSNPs in the AC3 gene. Single maker association analyses indicated that SNP rs753529 was significantly associated with BMI in obese subjects (P = 0.022, OR = 0.775 95%CI = 0.623–0.963), but not in overweight subjects (P = 0.818). Multiple maker association analyses showed that the haplotype (G-G-G) constructed with SNPs rs1127568, rs7604576 and rs753529 was significantly associated with obesity (P = 0.029). Further genotyping of SNP rs753529 in 816 children, including 361 overweight subjects (BMI>P₈₀) and 455 controls (BMI = P_20–50) were performed, and no significant association with BMI was found. All tests were adjusted for age, sex, physical activity index, household income and/or diet expenses.

Conclusions

The present study provides replication evidence that the AC3 genetic polymorphisms are associated with decreased risk of obesity among adults but not in children in a Chinese Han population. The data also suggest that the AC3 genetic effects on BMI may have interaction with the factors related to ageing and environment.     

Associations between XPD Asp312Asn polymorphism and risk of head and neck cancer: a meta-analysis based on 7,122 subjects

Background

To investigate the association between XPD Asp312Asn polymorphism and head and neck cancer risk through this meta-analysis.

Methods

We performed a meta-analysis of 9 published case-control studies including 2,670 patients with head and neck cancer and 4,452 controls. An odds ratio (OR) with a 95% confidence interval (CI) was applied to assess the association between XPD Asp312Asn polymorphism and head and neck cancer risk.

Results

Overall, no significant association between XPD Asp312Asn polymorphism and head and neck cancer risk was found in this meta-analysis (Asn/Asn vs. Asp/Asp: OR = 0.95, 95%CI = 0.80–1.13, P = 0.550, P _{heterogeneity} = 0.126; Asp/Asn vs. Asp/Asp: OR = 1.11, 95%CI = 0.99–1.24, P = 0.065, P _{heterogeneity} = 0.663; Asn/Asn+Asp/Asn vs. Asp/Asp: OR = 1.07, 95%CI = 0.97–1.19, P = 0.189, P _{heterogeneity} = 0.627; Asn/Asn vs. Asp/Asp+Asp/Asn: OR = 0.87, 95%CI = 0.68–1.10, P = 0.243, P _{heterogeneity} = 0.089). In the subgroup analysis by HWE, ethnicity, and study design, there was still no significant association detected in all genetic models.

Conclusions

This meta-analysis demonstrates that XPD Asp312Asn polymorphism may not be a risk factor for developing head and neck cancer.     

Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children

Background

The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268).

Methods and Findings

All studies identified to have data on the FTO rs9939609 variant (or any proxy [r ²>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A−) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20–1.26), but PA attenuated this effect (p _interaction  = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio  = 1.22/allele, 95% CI 1.19–1.25) than in the inactive group (odds ratio  = 1.30/allele, 95% CI 1.24–1.36). No such interaction was found in children and adolescents.

Conclusions

The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity. Please see later in the article for the Editors'' Summary     

Association of educational, occupational and socioeconomic status with cardiovascular risk factors in asian indians: a cross-sectional study

Background

To determine correlation of multiple parameters of socioeconomic status with cardiovascular risk factors in India.

Methods

The study was performed at eleven cities using cluster sampling. Subjects (n = 6198, men 3426, women 2772) were evaluated for socioeconomic, demographic, biophysical and biochemical factors. They were classified into low, medium and high socioeconomic groups based on educational level (<10, 10–15 and >15 yr formal education), occupational class and socioeconomic scale. Risk factor differences were evaluated using multivariate logistic regression.

Results

Age-adjusted prevalence (%) of risk factors in men and women was overweight or obesity in 41.1 and 45.2, obesity 8.3 and 15.8, high waist circumference 35.7 and 57.5, high waist-hip ratio 69.0 and 83.8, hypertension 32.5 and 30.4, hypercholesterolemia 24.8 and 25.3, low HDL cholesterol 34.1 and 35.1, high triglycerides 41.2 and 31.5, diabetes 16.7 and 14.4 and metabolic syndrome in 32.2 and 40.4 percent. Lifestyle factors were smoking 12.0 and 0.5, other tobacco use 12.7 and 6.3, high fat intake 51.2 and 48.2, low fruits/vegetables intake 25.3 and 28.9, and physical inactivity in 38.8 and 46.1%. Prevalence of > = 3 risk factors was significantly greater in low (28.0%) vs. middle (23.9%) or high (22.1%) educational groups (p<0.01). In low vs. high educational groups there was greater prevalence of high waist-hip ratio (odds ratio 2.18, confidence interval 1.65–2.71), low HDL cholesterol (1.51, 1.27–1.80), hypertriglyceridemia (1.16, 0.99–1.37), smoking/tobacco use (3.27, 2.66–4.01), and low physical activity (1.15, 0.97–1.37); and lower prevalence of high fat diet (0.47, 0.38–0.57),overweight/obesity (0.68, 0.58–0.80) and hypercholesterolemia (0.79, 0.66–0.94). Similar associations were observed with occupational and socioeconomic status.

Conclusions

Low educational, occupational and socioeconomic status Asian Indians have greater prevalence of truncal obesity, low HDL cholesterol, hypertriglyceridemia, smoking or tobacco use and low physical activity and clustering of > = 3 major cardiovascular risk factors.     

Ethnic Differences in Cardiometabolic Risk Profile at Age 5-6 Years: The ABCD Study

Background

To examine ethnic differences in cardiometabolic risk profile in early age, and explore whether such differences can be explained by differences in body mass index (BMI) or waist circumference (WC).

Method

Anthropometric measurements, blood pressure and (in a subsample) fasting blood were collected during a health check of 2,509 children aged 5–6 years. Four ethnic groups were distinguished: Dutch (n = 2,008; blood n = 1,300), African descent (n = 199; blood n = 105), Turkish (n = 108; blood n = 57) and Moroccan (n = 194; blood n = 94). Ethnic differences in diastolic and systolic blood pressure (DBP/SBP), fasting glucose, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride levels were determined and the explanatory role of BMI and WC was examined with regression analysis.

Results

After adjustment for confounders, African descent children showed higher DBP (β2.22 mmHg; 95%CI:1.09–3.36) and HDL levels (β:0.09 mmol/l; 95%CI:0.03–0.16) compared to Dutch children (reference group). Turkish children showed higher SBP (β:1.89 mmHg; 95%CI:0.25–3.54), DBP (β:2.62 mmHg; 95%CI:1.11–4.13), glucose (β:0.12 mmol/L; 95%CI:0.00–0.25) and triglyceride levels (β:0.13 mmol/L; 95%CI:0.02–0.25). Higher BMI values were found in all non–Dutch groups (differences ranged from 0.53–1.03 kg/m²) and higher WC in Turkish (β:1.68 cm; 95%CI:0.99–2.38) and Moroccan (β:1.65 cm; 95%CI:1.11–2.19) children. BMI and WC partly explained the higher SBP/DBP and triglyceride levels in Turkish children.

Conclusion

Ethnic differences in cardiometabolic profile exist early in life and are partly explained by differences in BMI and WC. African children showed favourable HDL levels and Turkish children the most unfavourable overall profile, whereas their Moroccan peers have less increased cardiometabolic risk in spite of their high BMI and WC.     

Relationship between a novel polymorphism of the C5L2 gene and coronary artery disease

Background

C5L2 has been demonstrated to be a functional receptor of acylation-stimulating protein (ASP), which is a stimulator of triglyceride synthesis or glucose transport. However, little is known about the variations in the coding region of the C5L2 gene and their association with coronary artery disease (CAD).

Methodology/Principal Findings

We identified a novel single nucleotide polymorphism (SNP), 698C>T (P233L), in exon 2 using a polymerase chain reaction direct-sequencing method. This nucleotide change causes the amino-acid order from proline to leucine at codon 233. We examined the role of this SNP for CAD using two independent case–control studies: one was in the Han population (492 CAD patients and 577 control subjects) and the other was in the Uygur population (319 CAD patients and 554 control subjects). Heterozygote carriers of the 698CT genotype were more frequent among CAD patients than among controls not only in the Han population (7.3% versus 1.7%) but also in the Uygur population (4.7% versus 1.6%). The odds ratio (OR) for carriers of the 698CT genotype for CAD was 4.484 (95% confidence interval (CI): 2.197–9.174) in the Han group and 2.989 (95% CI: 1.292–6.909) in the Uygur population. After adjustment of confounding factors such as sex, age, smoking, alcohol consumption, hypertension, diabetes, as well as serum levels of triglyceride, total cholesterol, high-density lipoprotein, the difference remained significant in the Han group (P<0.001, OR = 6.604, 95% CI: 2.776–15.711) and in the Uygur group (P = 0.047, OR = 2.602, 95% CI: 1.015–6.671).

Conclusion/Significance

The 698CT genotype of C5L2 may be a genetic maker of CAD in the Han and Uygur population in western China.     

The -675 4G/5G polymorphism in plasminogen activator inhibitor-1 gene is associated with risk of asthma: a meta-analysis

Background

A number of studies assessed the association of −675 4G/5G polymorphism in the promoter region of plasminogen activator inhibitor (PAI)-1 gene with asthma in different populations. However, most studies reported inconclusive results. A meta-analysis was conducted to investigate the association between polymorphism in the PAI-1 gene and asthma susceptibility.

Methods

Databases including Pubmed, EMBASE, HuGE Literature Finder, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Weipu Database were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the dominant model, recessive model, codominant model, and additive model.

Results

Eight studies involving 1817 cases and 2327 controls were included. Overall, significant association between 4G/5G polymorphism and asthma susceptibility was observed for 4G4G+4G5G vs. 5G5G (OR = 1.56, 95% CI 1.12–2.18, P = 0.008), 4G/4G vs. 4G/5G+5G/5G (OR = 1.38, 95% CI 1.06–1.80, P = 0.02), 4G/4G vs. 5G/5G (OR = 1.80, 95% CI 1.17–2.76, P = 0.007), 4G/5G vs. 5G/5G (OR = 1.40, 95% CI 1.07–1.84, P = 0.02), and 4G vs. 5G (OR = 1.35, 95% CI 1.08–1.68, P = 0.008).

Conclusions

This meta-analysis suggested that the −675 4G/5G polymorphism of PAI-1 gene was a risk factor of asthma.     

Association of the myostatin gene with obesity, abdominal obesity and low lean body mass and in non-diabetic asian indians in north India

Background

To determine the association of the A55T and K153R polymorphisms of the Myostatin gene with obesity, abdominal obesity and lean body mass (LBM) in Asian Indians in north India.

Materials and Methods

A total of 335 subjects (238 men and 97 women) were assessed for anthropometry, % body fat (BF), LBM and biochemical parameters. Associations of Myostatin gene polymorphisms were evaluated with anthropometric, body composition and biochemical parameters. In A55T polymorphism, BMI (p = 0.04), suprailiac skinfold (p = 0.05), total skinfold (p = 0.008), %BF (p = 0.002) and total fat mass (p = 0.003) were highest and % LBM (p = 0.03) and total LBM (Kg) were lowest (p = 0.04) in subjects with Thr/Thr genotype as compared to other genotypes. Association analysis of K153R polymorphism showed that subjects with R/R genotype had significantly higher BMI (p = 0.05), waist circumference (p = 0.04), %BF (p = 0.04) and total fat mass (p = 0.03), and lower %LBM (p = 0.02) and total LBM [(Kg), (p = 0.04)] as compared to other genotypes. Using a multivariate logistic regression model after adjusting for age and sex, subjects with Thr/Thr genotype of A55T showed high risk for high %BF (OR, 3.92, 95% Cl: 2.61–12.41), truncal subcutaneous adiposity (OR, 2.9, 95% Cl: 1.57–6.60)] and low LBM (OR, 0.64, 95% CI: 0.33–0.89) whereas R/R genotype of K153R showed high risk of obesity (BMI; OR, 3.2, 95% CI: 1.2–12.9; %BF, OR, 3.6, 95% CI: 1.04–12.4), abdominal obesity (OR, 2.12, 95% CI: 2.71–14.23) and low LBM (OR, 0.61, 95% CI: 0.29–0.79).

Conclusions/Significance

We report that variants of Myostatin gene predispose to obesity, abdominal obesity and low lean body mass in Asian Indians in north India.     

Allelic variants of melanocortin 3 receptor gene (MC3R) and weight loss in obesity: a randomised trial of hypo-energetic high- versus low-fat diets

Introduction

The melanocortin system plays an important role in energy homeostasis. Mice genetically deficient in the melanocortin-3 receptor gene have a normal body weight with increased body fat, mild hypophagia compared to wild-type mice. In humans, Thr6Lys and Val81Ile variants of the melanocortin-3 receptor gene (MC3R) have been associated with childhood obesity, higher BMI Z-score and elevated body fat percentage compared to non-carriers. The aim of this study is to assess the association in adults between allelic variants of MC3R with weight loss induced by energy-restricted diets.

Subjects and Methods

This research is based on the NUGENOB study, a trial conducted to assess weight loss during a 10-week dietary intervention involving two different hypo-energetic (high-fat and low-fat) diets. A total of 760 obese patients were genotyped for 10 single nucleotide polymorphisms covering the single exon of MC3R gene and its flanking regions, including the missense variants Thr6Lys and Val81Ile. Linear mixed models and haplotype-based analysis were carried out to assess the potential association between genetic polymorphisms and differential weight loss, fat mass loss, waist change and resting energy expenditure changes.

Results

No differences in drop-out rate were found by MC3R genotypes. The rs6014646 polymorphism was significantly associated with weight loss using co-dominant (p = 0.04) and dominant models (p = 0.03). These p-values were not statistically significant after strict control for multiple testing. Haplotype-based multivariate analysis using permutations showed that rs3827103–rs1543873 (p = 0.06), rs6014646–rs6024730 (p = 0.05) and rs3746619–rs3827103 (p = 0.10) displayed near-statistical significant results in relation to weight loss. No other significant associations or gene*diet interactions were detected for weight loss, fat mass loss, waist change and resting energy expenditure changes.

Conclusion

The study provided overall sufficient evidence to support that there is no major effect of genetic variants of MC3R and differential weight loss after a 10-week dietary intervention with hypo-energetic diets in obese Europeans.     

Genetic variations in a PTEN/AKT/mTOR axis and prostate cancer risk in a Chinese population

Backgroud

Genetic variations in a PTEN/AKT/mTOR signaling axis may influence cellular functions including cell growth, proliferation and apoptosis, and then increase the individual’s risk of cancer. Accordingly, we explore the association between single nucleotide polymorphisms (SNPs) of these genes and prostate cancer (PCa) in our Chinese population.

Methods

Subjects were recruited from 666 PCa patients and 708 cancer-free controls, and eight SNPs in the PTEN/AKT/mTOR axis were determined by the TaqMan assay. Odds ratios (OR) and 95% confidence intervals (95% CI) were evaluated by logistic regression.

Results

We observed significant associations between PCa risk and mTOR rs2295080 [P = 0.027, OR = 0.85, 95%CI = 0.74–0.98], and AKT2 rs7254617 (P = 0.003, OR = 1.35, 95%CI = 1.11–1.64). When estimated these two SNPs together, the combined genotypes with 2–4 risk alleles (rs2295080 T and rs7254617 A alleles) were associated with an increased risk of PCa compared with 0–1 risk alleles, which was more pronounced among subgroups of age >71 years, smokers, drinkers and no family history of cancer. Results of stratified analyses by cliniopathological parameters revealed that the frequencies of the combined genotypes with 2–4 risk alleles in advanced stage were significantly higher than in localized stage(P = 0.022), but there was no significant association in Gleason score and PSA level.

Conclusion

Our results indicate, for the first time that the two variants in AKT2 and mTOR, particularly the joint genotypes with 2–4 risk alleles may influence PCa susceptibility and progression in Chinese, and the association appeared to be more strong in the subgroup of smokers and drinkers.     

Dietary Factors Impact on the Association between CTSS Variants and Obesity Related Traits

Background/Aims

Cathepsin S, a protein coded by the CTSS gene, is implicated in adipose tissue biology–this protein enhances adipose tissue development. Our hypothesis is that common variants in CTSS play a role in body weight regulation and in the development of obesity and that these effects are influenced by dietary factors–increased by high protein, glycemic index and energy diets.

Methods

Four tag SNPs (rs7511673, rs11576175, rs10888390 and rs1136774) were selected to capture all common variation in the CTSS region. Association between these four SNPs and several adiposity measurements (BMI, waist circumference, waist for given BMI and being a weight gainer–experiencing the greatest degree of unexplained annual weight gain during follow-up or not) given, where applicable, both as baseline values and gain during the study period (6–8 years) were tested in 11,091 European individuals (linear or logistic regression models). We also examined the interaction between the CTSS variants and dietary factors–energy density, protein content (in grams or in % of total energy intake) and glycemic index–on these four adiposity phenotypes.

Results

We found several associations between CTSS polymorphisms and anthropometric traits including baseline BMI (rs11576175 (SNP N°2), p = 0.02, β = −0.2446), and waist change over time (rs7511673 (SNP N°1), p = 0.01, β = −0.0433 and rs10888390 (SNP N°3), p = 0.04, β = −0.0342). In interaction with the percentage of proteins contained in the diet, rs11576175 (SNP N°2) was also associated with the risk of being a weight gainer (p_interaction = 0.01, OR = 1.0526)–the risk of being a weight gainer increased with the percentage of proteins contained in the diet.

Conclusion

CTSS variants seem to be nominally associated to obesity related traits and this association may be modified by dietary protein intake.     

Pulmonary function and incident bronchitis and asthma in children: a community-based prospective cohort study

Background

Previous studies revealed that reduction of airway caliber in infancy might increase the risks for wheezing and asthma. However, the evidence for the predictive effects of pulmonary function on respiratory health in children was still inconsistent.

Methods

We conducted a population-based prospective cohort study among children in 14 Taiwanese communities. There were 3,160 children completed pulmonary function tests in 2007 and follow-up questionnaire in 2009. Poisson regression models were performed to estimate the effect of pulmonary function on the development of bronchitis and asthma.

Results

After adjustment for potential confounders, pulmonary function indices consistently showed protective effects on respiratory diseases in children. The incidence rate ratios of bronchitis and asthma were 0.86 (95% CI 0.79–0.95) and 0.91 (95% CI 0.82–0.99) for forced expiratory volume in 1 second (FEV₁). Similar adverse effects of maximal mid-expiratory flow (MMEF) were also observed on bronchitis (RR = 0.73, 95% CI 0.67–0.81) and asthma (RR = 0.85, 95% CI 0.77–0.93). We found significant decreasing trends in categorized FEV₁ (p for trend = 0.02) and categories of MMEF (p for trend = 0.01) for incident bronchitis. Significant modification effects of traffic-related air pollution were noted for FEV₁ and MMEF on bronchitis and also for MMEF on asthma.

Conclusions

Children with high pulmonary function would have lower risks on the development of bronchitis and asthma. The protective effect of high pulmonary function would be modified by traffic-related air pollution exposure.     

Higher Fetal Insulin Resistance in Chinese Pregnant Women with Gestational Diabetes Mellitus and Correlation with Maternal Insulin Resistance

Objective

The aim of this study was to determine the effect of gestational diabetes mellitus (GDM) on fetal insulin resistance or β-cell function in Chinese pregnant women with GDM.

Measurements

Maternal fasting blood and venous cord blood samples (reflecting fetal condition) were collected in 65 well-controlled Chinese GDM mothers (only given dietary intervention) and 83 control subjects. The insulin, glucose and proinsulin concentrations of both maternal and cord blood samples were measured, and the homeostasis model assessment of insulin resistance (HOMA-IR) and the proinsulin-to-insulin ratios (an indicator of fetal β-cell function) were calculated in maternal and cord blood respectively.

Results

Both maternal and fetal levels of insulin, proinsulin and HOMA-IR but not proinsulin-to-insulin ratios were significantly higher in the GDM group than in the control group (maternal insulin, 24.8 vs. 15.4 µU/mL, P = 0.004, proinsulin, 23.3 vs. 16.2 pmol/L, P = 0.005, and HOMA-IR, 5.5 vs. 3.5, P = 0.041, respectively; fetal: insulin, 15.1 vs. 7.9 µU/mL, P<0.001, proinsulin, 25.8 vs. 15.1 pmol/L, P = 0.015, and HOMA-IR, 2.8 vs. 1.4, P = 0.017, respectively). Fetal HOMA-IR but not proinsulin-to-insulin ratios was significantly correlated to maternal HOMA-IR (r = 0.307, P = 0.019), in the pregnant women with GDM.

Conclusions

Fetal insulin resistance was higher in Chinese pregnant women with GDM than control subjects, and correlated with maternal insulin resistance.     

U-Curve Association between Timing of Renal Replacement Therapy Initiation and In-Hospital Mortality in Postoperative Acute Kidney Injury

Background

Postoperative acute kidney injury (AKI) is associated with poor outcomes in surgical patients. This study aims to evaluate whether the timing of renal replacement therapy (RRT) initiation affects the in-hospital mortality of patients with postoperative AKI.

Methodology

This multicenter retrospective observational study, which was conducted in the intensive care units (ICUs) in a tertiary hospital (National Taiwan University Hospital) and its branch hospitals in Taiwan between January, 2002, and April, 2009, included adult patients with postoperative AKI who underwent RRT for predefined indications. The demographic data, comorbid diseases, types of surgery and RRT, and the indications for RRT were documented. Patients were categorized according to the period of time between the ICU admission and RRT initiation as the early (EG, ≦1 day), intermediate (IG, 2–3 days), and late (LG, ≧4 days) groups. The in-hospital mortality rate censored at 180 day was defined as the endpoint.

Results

Six hundred forty-eight patients (418 men, mean age 63.0±15.9 years) were enrolled, and 379 patients (58.5%) died during the hospitalization. Both the estimated probability of death and the in-hospital mortality rates of the three groups represented U-curves. According to the Cox proportional hazard method, LG (hazard ratio, 1.527; 95% confidence interval, 1.152–2.024; P = 0.003, compared with IG group), age (1.014; 1.006–1.021), diabetes (1.279; 1.022–1.601; P = 0.031), cirrhosis (2.147; 1.421–3.242), extracorporeal membrane oxygenation support (1.811; 1.391–2.359), initial neurological dysfunction (1.448; 1.107–1.894; P = 0.007), pre-RRT mean arterial pressure (0.988; 0.981–0.995), inotropic equivalent (1.006; 1.001–1.012; P = 0.013), APACHE II scores (1.055; 1.037–1.073), and sepsis (1.939; 1.536–2.449) were independent predictors of the in-hospital mortality (All P<0.001 except otherwise stated).

Conclusions

The current study found a U-curve association between the timing of the RRT initiation after the ICU admission and patients’ in-hospital mortalities, and alerts physicians of certain factors affecting the outcome after the RRT initiation.     

Association of microRNA-499 rs3746444 Polymorphism with Cancer Risk: Evidence from 7188 Cases and 8548 Controls

Background

Owing to inconsistent and inconclusive results, we performed a meta-analysis to derive a more precise estimation of the association between miR-499 rs3746444 polymorphism and cancer risk.

Methodology/Principal Findings

A systematic search of the Pubmed, Excerpta Medica Database (Embase) and Chinese Biomedical Literature Database (CBM) databases was performed with the last search updated on May 6, 2012. The odds ratio (OR) and its 95% confidence interval (95%CI) were used to assess the strength of the association. A total of 15 independent studies including 7,188 cases and 8,548 controls were used in the meta-analysis. In the present meta-analysis, we found a significant association between miR-499 rs3746444 polymorphism and cancer risk in the overall analysis (G versus A: OR = 1.10, 95%CI 1.01–1.19, P = 0.03; GG+AG versus AA: OR = 1.15, 95%CI 1.02–1.30, P = 0.02; GG versus AG+AA: OR = 1.07, 95%CI 0.89–1.28, P = 0.50; GG versus AA: OR = 1.13, 95%CI 0.98–1.31, P = 0.09; AG versus AA: OR = 1.16, 95%CI 1.02–1.33, P = 0.03). In the subgroup analysis by ethnicity, miR-499 rs3746444 polymorphism was significantly associated with cancer risk in Asian population. In the subgroup analysis by cancer types, miR-499 rs3746444 polymorphism was significantly associated with breast cancer.

Conclusions/Significance

This meta-analysis suggests a significant association between miR-499 rs3746444 polymorphism and cancer risk. Large-scale and well-designed case-control studies are necessary to validate the risk identified in the present meta-analysis.