Detailed analysis of variants in FTO in association with body composition in a cohort of 70-year-olds suggests a weakened effect among elderly

Background

The rs9939609 single-nucleotide polymorphism (SNP) in the fat mass and obesity (FTO) gene has previously been associated with higher BMI levels in children and young adults. In contrast, this association was not found in elderly men. BMI is a measure of overweight in relation to the individuals'' height, but offers no insight into the regional body fat composition or distribution.

Objective

To examine whether the FTO gene is associated with overweight and body composition-related phenotypes rather than BMI, we measured waist circumference, total fat mass, trunk fat mass, leg fat mass, visceral and subcutaneous adipose tissue, and daily energy intake in 985 humans (493 women) at the age of 70 years. In total, 733 SNPs located in the FTO gene were genotyped in order to examine whether rs9939609 alone or the other SNPs, or their combinations, are linked to obesity-related measures in elderly humans.

Design

Cross-sectional analysis of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort.

Results

Neither a single SNP, such as rs9939609, nor a SNP combination was significantly linked to overweight, body composition-related measures, or daily energy intake in elderly humans. Of note, these observations hold both among men and women.

Conclusions

Due to the diversity of measurements included in the study, our findings strengthen the view that the effect of FTO on body composition appears to be less profound in later life compared to younger ages and that this is seemingly independent of gender.     

FTO Gene Variant and Risk of Overweight and Obesity among Children and Adolescents: a Systematic Review and Meta-Analysis

Objective

The fat mass and obesity associated gene (FTO) polymorphisms have been implicated in the susceptibility of overweight/obesity in children and adolescents. However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association of FTO gene polymorphisms with overweight/obesity risk among children and adolescents.

Methods

PubMed and Embase were used to search for eligible published literatures. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random- or fixed-effect models.

Results

A total of 21 articles containing 23 studies (11208cases and 35015controls) were included in our analysis. The results indicated that variant in FTO gene was significantly associated with increased risk of overweight/obesity in children and adolescents (OR=1.35; 95%CI: 1.27-1.44; P<0.001). The overall pooled ORs for risk obesity and overweight were 1.34 (95%CI: 1.21-1.48) and 1.35 (95%CI: 1.25-1.47), respectively. Subgroup analyses also showed similar trends in most subgroups of adjustment for covariates and unadjustment, different ethnicities (Caucasians, Asians, and Amerindians), and each of three investigated polymorphisms (rs9939609, rs1421085, and rs1558902).

Conclusions

The present meta-analysis suggested a positive association between FTO gene polymorphism and overweight/obesity risk among children and adolescents. Further prospective studies should be recommended to confirm the observed association, and underlying mechanism should be investigated to clarify the association of FTO gene polymorphism with overweight/obesity.     

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.     

Child Behavioural Problems and Body Size among 2-6 Year Old Children Predisposed to Overweight. Results From the “Healthy Start” Study

Objective

Psychological adversities among young children may be associated with childhood overweight and obesity. We examined if an increased level of child behavioural problems was associated with body size among a selected group of 2-6 year old children, who were all predisposed to develop overweight.

Methods

Cross-sectional analyses were conducted using baseline data from the “Healthy Start” intervention study. A total of 3058 children were invited to participate, and data from 583 children who were all predisposed for obesity was analyzed. The Danish version of the Strengths and Difficulties Questionnaire (SDQ) was used to assess child stress by the SDQ Total Difficulties (SDQ-TD) score and the Prosocial Behavior (PSB) score. Height and weight were measured, and BMI z-scores were calculated.

Results

A direct, but non-significant linear trend was found between SDQ-TD score and BMI z-score (β = 0.021, p = 0.11). Having an SDQ-TD score above the 90^th percentile was associated with BMI z-score (β = 0.36, p = 0.05). PSB score was not associated with BMI z-score. Analyses were adjusted for parental socioeconomic status, parental BMI, family structure, dietary factors, physical activity, and family stress level.

Conclusion

The results suggested a threshold effect between SDQ-TD score and BMI z-score, where BMI z-score was associated with childhood behavioural problems only for those with the highest scores of SDQ-TD. No significant association between PSB score and BMI z-score was found.     

Novel Single Nucleotide Polymorphism Markers for Low Dose Aspirin-Associated Small Bowel Bleeding

Background

Aspirin-induced enteropathy is now increasingly being recognized although the pathogenesis of small intestinal damage induced by aspirin is not well understood and related risk factors have not been established.

Aim

To investigate pharmacogenomic profile of low dose aspirin (LDA)-induced small bowel bleeding.

Methods

Genome-wide analysis of single nucleotide polymorphisms (SNPs) was performed using the Affymetrix DMET™ Plus Premier Pack. Genotypes of candidate genes associated with small bowel bleeding were determined using TaqMan SNP Genotyping Assay kits and direct sequencing.

Results

In the validation study in overall 37 patients with small bowel bleeding and 400 controls, 4 of 27 identified SNPs: CYP4F11 (rs1060463) GG (p=0.003), CYP2D6 (rs28360521) GG (p=0.02), CYP24A1 (rs4809957) T allele (p=0.04), and GSTP1 (rs1695) G allele (p=0.04) were significantly more frequent in the small bowel bleeding group compared to the controls. After adjustment for significant factors, CYP2D6 (rs28360521) GG (OR 4.11, 95% CI. 1.62 -10.4) was associated with small bowel bleeding.

Conclusions

CYP4F11 and CYP2D6 SNPs may identify patients at increased risk for aspirin-induced small bowel bleeding.     

Appropriate Body Mass Index and Waist Circumference Cutoffs for Categorization of Overweight and Central Adiposity among Uighur Adults in Xinjiang

Objective

The current overweight and central adiposity guidelines based on Western populations were not consistent with many studied based on the Asian populations. Uighur people live in Xinjiang Uighur Autonomous Region which is located in the center of Asia. Their overweight and central cutoffs were largely unknown. We aimed to identify cutoffs for body mass index (BMI; in kg/m²) and waist circumference (WC; in cm) for categorization of overweight and central adiposity among Uighur adults in Xinjiang.

Methods

4767 Uighur participants were selected from the Cardiovascular Risk Survey (CRS) which was carried out from October 2007 to March 2010. The age of the participants were from 35 to 101 years old with the mean age of 50.09 years. Anthropometric data, blood pressure, serum concentration of serum total cholesterol, triglyceride, low density lipoprotein (LDL), high density lipoprotein (HDL) and fasting glucose were documented. The prevalence, sensitivity, specificity and distance on the receiver operating characteristic (ROC) curve of each BMI and waist circumference values were calculated.

Results

The prevalence of hypertension, hypercholesterolemia and hypertriglyceridemia were higher with higher BMI for both men and women. The prevalence of hypertension and hypercholesterolemia were higher with higher waist circumference for both men and women. In women, the prevalence of hypertriglyceridemia was noticed to increase as the waist circumference increased. The shortest distance in the receiver operating characteristic curves for hypertension, dyslipidemia, diabetes, or ≥ 2 of these risk factors suggested a BMI cutoff of 26 and a waist circumference cutoff of 90 cm for both men and women.

Conclusions

Higher cutoffs for BMI and waist circumference are needed in the identification of Uighur patients at high risk of cardiovascular disease.     

The Importance of Gender of Patients and General Practitioners in Relation to Treatment Practices for Overweight

Background

Several studies suggest that men and women are treated differently for similar disease including diabetes and cardiovascular disease. Differences in attitudes and treatment practices towards men and women with obesity are not well recognized.

Objective

To investigate the attitudes and treatment practices among Danish general practitioners (GPs), in relation to treatment of overweight, while taking gender of both the patients and practitioners into account.

Design

Questionnaire inventory covertly examining attitudes and practices among Danish general practitioners towards treatment of overweight. All 3.637 general practitioners from the Danish Medical Association register were invited to participate in the survey. In total 1.136 participated.

Results

The GPs found weight loss to be more important for overweight male than overweight female patients. They also treated complications to overweight more rigorously among male than female patients, and recommended lipid lowering medicine more often to male than female overweight patients. In addition, the younger female GPs and older male GPs more often said that they would treat an overweight patient with lipid lowering medicine.

Conclusion

Among general practitioners in Denmark, treatment for weight loss is more often practiced for overweight male than overweight female patients presenting with same symptoms. In addition, hyperlipidemia among overweight males is also more often treated with lipid lowering medicine than hyperlipidemia among overweight females.     

Genetic Variation in SULF2 Is Associated with Postprandial Clearance of Triglyceride-Rich Remnant Particles and Triglyceride Levels in Healthy Subjects

Context

Nonfasting (postprandial) triglyceride concentrations have emerged as a clinically significant cardiovascular disease risk factor that results from accumulation of remnant triglyceride-rich lipoproteins (TRLs) in the circulation. The remnant TRLs are cleared from the circulation by hepatic uptake, but the specific mechanisms involved are unclear. The syndecan-1 heparan sulfate proteoglycan (HSPG) pathway is important for the hepatic clearance of remnant TRLs in mice, but its relevance in humans is unclear.

Objective

We sought to determine whether polymorphisms of the genes responsible for HSPG assembly and disassembly contribute to atherogenic dyslipoproteinemias in humans.

Patients And Design

We performed an oral fat load in 68 healthy subjects. Lipoproteins (chylomicrons and very low density lipoproteins 1 and 2) were isolated from blood, and the area under curve and incremental area under curve for postprandial variables were calculated. Single nucleotide polymorphisms in genes encoding syndecan-1 and enzymes involved in the synthesis or degradation of HSPG were genotyped in the study subjects.

Results

Our results indicate that the genetic variation rs2281279 in SULF2 associates with postprandial clearance of remnant TRLs and triglyceride levels in healthy subjects. Furthermore, the SNP rs2281279 in SULF2 associates with hepatic SULF2 mRNA levels.

Conclusions

In humans, mild but clinically relevant postprandial hyperlipidemia due to reduced hepatic clearance of remnant TRLs may result from genetic polymorphisms that affect hepatic HSPG.     

Maternal Prepregnancy Body Mass Index and Gestational Weight Gain on Offspring Overweight in Early Infancy

Objective

The aim of the present study was to evaluate the association of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) with anthropometry in the offspring from birth to 12 months old in Tianjin, China.

Methods

Between 2009 and 2011, health care records of 38,539 pregnant women had been collected, and their children had been measured body weight and length at birth, 3, 6, 9 and 12 months of age. The independent and joint associations of pre-pregnancy BMI and GWG based on the Institute of Medicine (IOM) guidelines with anthropometry in the offspring were examined using General Linear Model and Logistic Regression.

Results

Prepregnancy BMI and maternal GWG were positively associated with Z-scores for birth weight-for-gestational age, birth length-for-gestational age, and birth weight-for-length. Infants born to mothers with excessive GWG had the greatest changes in Z-scores for weight-for-age from birth to Month 3, and from Month 6 to Month 12, and the greatest changes in Z-scores for length-for-age from birth to months 3 and 12 compared with infants born to mothers with adequate GWG. Excessive GWG was associated with an increased risk of offspring overweight or obesity at 12 months old in all BMI categories except underweight.

Conclusions

Maternal prepregnancy overweight/obesity and excessive GWG were associated with greater weight gain and length gain of offspring in early infancy. Excessive GWG was associated with increased infancy overweight and obesity risk.     

Association Analysis of Genetic Variants in the Myosin IXB Gene in Acute Pancreatitis

Introduction

Impairment of the mucosal barrier plays an important role in the pathophysiology of acute pancreatitis. The myosin IXB (MYO9B) gene and the two tight-junction adaptor genes, PARD3 and MAGI2, have been linked to gastrointestinal permeability. Common variants of these genes are associated with celiac disease and inflammatory bowel disease, two other conditions in which intestinal permeability plays a role. We investigated genetic variation in MYO9B, PARD3 and MAGI2 for association with acute pancreatitis.

Methods

Five single nucleotide polymorphisms (SNPs) in MYO9B, two SNPs in PARD3, and three SNPs in MAGI2 were studied in a Dutch cohort of 387 patients with acute pancreatitis and over 800 controls, and in a German cohort of 235 patients and 250 controls.

Results

Association to MYO9B and PARD3 was observed in the Dutch cohort, but only one SNP in MYO9B and one in MAGI2 showed association in the German cohort (p < 0.05). Joint analysis of the combined cohorts showed that, after correcting for multiple testing, only two SNPs in MYO9B remained associated (rs7259292, p = 0.0031, odds ratio (OR) 1.94, 95% confidence interval (95% CI) 1.35-2.78; rs1545620, p = 0.0006, OR 1.33, 95% CI 1.16-1.53). SNP rs1545620 is a non-synonymous SNP previously suspected to impact on ulcerative colitis. None of the SNPs showed association to disease severity or etiology.

Conclusion

Variants in MYO9B may be involved in acute pancreatitis, but we found no evidence for involvement of PARD3 or MAGI2.     

The Apolipoprotein E Polymorphism rs7412 Associates with Body Fatness Independently of Plasma Lipids in Middle Aged Men

Background

The apolipoprotein E (APOE) gene is polymorphic, encoding one of 3 common alleles (ε2, ε3, ε4) produced from combinations of 2 non-synonymous SNPs (rs429358 and rs7412). APOE plays an important role controlling plasma lipids but its association with adipocyte functionality and body fatness remains to be determined.

Methods

We analyzed fasting plasma lipids and genotyped the two main APOE-SNPs (rs429358 and rs7412), both located in the fourth exon of the APOE, in 4660 Caucasian middle-aged men free of cardiovascular disease.

Results

The rs7412 SNP, which determines the APOE2 isoform, was significantly associated with Body Mass Index (BMI) and Waist Girth (WG) in a multivariate model accounting for age, smoking status and plasma lipids. BMI and WG were highest in TT homozygotes and lowest in CC homozygotes. This effect was independent of the rs429358 SNP, which failed to show any association with the BMI and WG variables. The odds ratio of being obese (BMI>30) for individuals carrying the APOε2 allele, present in 14% of the cohort and defined by the rs7412 SNP, was also significant in this multivariate model, with an OR of 1.27 (95% CI: 1.01–1.59).

Conclusions

This study provides an evidence of a lipid-independent association between the APOE SNP rs7412 and body fatness surrogates, BMI and WG, in a large cohort of middle-aged males.     

Obesity and Dental Decay: Inference on the Role of Dietary Sugar

Objective

To evaluate the relationship of children’s obesity and dental decay.

Methods

We measured parameters related to obesity and dental decay in 8,275 4^th and 5^th grade Kuwaiti children (average age = 11.36 years) in a cross-sectional study. First to determine body weight, height, age for computation of BMI . Second, to determine numbers of teeth, numbers of fillings and numbers of untreated decayed teeth to determine extent and severity of dental disease. From these measurements, we computed measures of dental decay in children from four body weight categories; obese, overweight, normal healthy weight and underweight children.

Results

The percentage of children with decayed or filled teeth varied inversely with the body weight category. The percentage of decayed or filled teeth decreased from 15.61% (n=193) in underweight children, to 13.03% (n=4,094) in normal healthy weight children, to 9.73% (n=1,786) in overweight children to 7.87% (n=2,202) in obese children. Differences between all groups were statistically significant. Male children in this population had more dental decay than female children but the reduction of tooth decay as a function of BMI was greater in male children.

Conclusions

The finding of an inverse obesity-dental decay relationship contradicts the obesity-sugar and the obesity-dental decay relationship hypotheses. Sugar is well recognized as necessary and sufficient for dental decay. Sugar is also hypothesized to be a leading co-factor in obesity. If the later hypothesis is true, one would expect dental decay to increase with obesity. This was not found. The reasons for this inverse relationship are not currently clear.     

Association of LIN28B with Adult Adiposity-Related Traits in Females

Context

Pubertal timing is under strong genetic control and its early onset associates with several adverse health outcomes in adulthood, including obesity, type 2 diabetes and cardiovascular disease. Recent data indicate strong association between pubertal timing and genetic variants near LIN28B, but it is currently unknown whether the gene contributes to the association between puberty and adult disease.

Objective

To elucidate the putative genetic link between early puberty and adult disease risk, we examined the association of two genetic variants near LIN28B with adult body size and metabolic profiles in randomly ascertained adult Finnish males and females.

Methods

Two single nucleotide polymorphisms (SNPs), rs7759938, the lead SNP previously associated with pubertal timing and height, and rs314279, previously also associated with menarcheal age but only partially correlated with rs7759938 (r² = 0.30), were genotyped in 26,636 study subjects participating in the Finnish population survey FINRISK. Marker associations with adult height, weight, body mass index (BMI), hip and waist circumference, blood glucose, serum insulin and lipid/lipoprotein levels were determined by linear regression analyses.

Results

Both rs7759938 and rs314279 associated with adult height in both sexes (p = 2×10⁻⁶ and p = 0.001). Furthermore, rs314279 associated with increased weight in females (p = 0.001). Conditioned analyses including both SNPs in the regression model verified that rs314279 independently associates with adult female weight, BMI and hip circumference (p<0.005). Neither SNP associated with glucose, lipid, or lipoprotein levels.

Conclusion

Genetic variants near the puberty-associated gene LIN28B associate with adult weight and body shape in females, suggesting that the gene may tag molecular pathways influencing adult adiposity-related traits.     

Association of TERC and OBFC1 Haplotypes with Mean Leukocyte Telomere Length and Risk for Coronary Heart Disease

Objective

To replicate the associations of leukocyte telomere length (LTL) with variants at four loci and to investigate their associations with coronary heart disease (CHD) and type II diabetes (T2D), in order to examine possible causal effects of telomere maintenance machinery on disease aetiology.

Methods

Four SNPs at three loci BICD1 (rs2630578 GγC), 18q12.2 (rs2162440 GγT), and OBFC1 (rs10786775 CγG, rs11591710 AγC) were genotyped in four studies comprised of 2353 subjects out of which 1148 had CHD and 566 T2D. Three SNPs (rs12696304 CγG, rs10936601G>T and rs16847897 GγC) at the TERC locus were genotyped in these four studies, in addition to an offspring study of 765 healthy students. For all samples, LTL had been measured using a real-time PCR-based method.

Results

Only one SNP was associated with a significant effect on LTL, with the minor allele G of OBFC1 rs10786775 SNP being associated with longer LTL (β=0.029, P=0.04). No SNPs were significantly associated with CHD or T2D. For OBFC1 the haplotype carrying both rare alleles (rs10786775G and rs11591710C, haplotype frequency 0.089) was associated with lower CHD prevalence (OR: 0.77; 95% CI: 0.61–0.97; P= 0.03). The TERC haplotype GTC (rs12696304G, rs10936601T and rs16847897C, haplotype frequency 0.210) was associated with lower risk for both CHD (OR: 0.86; 95% CI: 0.75-0.99; P=0.04) and T2D (OR: 0.74; 95% CI: 0.61–0.91; P= 0.004), with no effect on LTL. Only the last association remained after adjusting for multiple testing.

Conclusion

Of reported associations, only that between the OBFC1 rs10786775 SNP and LTL was confirmed, although our study has a limited power to detect modest effects. A 2-SNP OBFC1 haplotype was associated with higher risk of CHD, and a 3-SNP TERC haplotype was associated with both higher risk of CHD and T2D. Further work is required to confirm these results and explore the mechanisms of these effects.     

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.     

Maternal Prepregancy BMI and Lipid Profile during Early Pregnancy Are Independently Associated with Offspring's Body Composition at Age 5–6 Years: The ABCD Study

Background

There is growing evidence that disturbances in maternal metabolism and, subsequently, intrauterine conditions affect foetal metabolism. Whether this has metabolic consequences in offspring later in life is not fully elucidated. We investigated whether maternal pre-pregnancy body mass index (pBMI) is associated with offspring''s adiposity at age 5–6 years and whether this association is mediated by the mother''s lipid profile during early pregnancy.

Methods

Data were derived from a multi-ethnic birth cohort, the Amsterdam Born Children and their Development (ABCD) study (inclusion 2003–2004). During early gestation mothers completed a questionnaire during pregnancy (pBMI) and random non-fasting blood samples were analysed for total cholesterol (TC), triglycerides (TG), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and total free fatty acids (FFA) in early gestation. At age 5–6 years, child''s BMI, waist-to-height-ratio (WHtR) and fat% were assessed.

Results

Only non-diabetic mothers with at term-born children were included(n = 1727). Of all women, 15.1% were overweight(BMI: 25–29.9 kg/m2) and 4.3% were obese(BMI≥30 kg/m2). After adjustments for confounders, every unit increase in pBMI was linearly associated with various offspring variables: BMI(β 0.10; 95% CI 0.08–0.12), WHtR*100(β 0.13; 95% CI 0.09–0.17), fat%(β 0.21; 95% CI 0.13–0.29) and increased risk for overweight(OR:1.15; 95% CI 1.10–1.20). No convincing proof for mediation by maternal lipid profile during early gestation was found. Moreover, maternal FFA was associated with the child''s fat percentage, BMI and risk for overweight. Maternal ApoB and TC were positively associated with the offspring''s fat percentage and maternal TG was positively associated with their children''s WHtR.

Conclusions

Both pBMI and maternal lipids during early pregnancy are independently related to offspring adiposity.     

Body Mass Index Development from Birth to Early Adolescence; Effect of Perinatal Characteristics and Maternal Migration Background in a Swedish Cohort

Background

Well documented diversity in risk of developing overweight and obesity between children of immigrant and of native mothers, might be explained by different body mass index (BMI) development trajectories in relation to maternal and perinatal characteristics of offspring.

Objectives

To assess BMI development trajectories among children born to immigrant and to Swedish mothers from birth to adolescence in relation to perinatal characteristics.

Methods

A cohort of 2517 children born in Stockholm during 1994 to 1996 was followed with repeated measurement of height and weight at eleven time points until age 12 years. We estimated changes over time for BMI in relation to maternal and perinatal characteristics of offspring using mixed linear model analysis for repeated measure data.

Results

We observed a significant BMI change over time in children and time interaction with maternal migration status (P<0.0001). Estimated BMI over time adjusted for maternal and perinatal characteristics of offspring, showed slower BMI growth before age of 5, followed by an earlier plateau and steeper BMI growth after 5 years among children of immigrant mothers compared with children of Swedish mothers. These differences in BMI growth were more prominent among children with mothers from outside Europe.

Conclusion

Beside reinforcing early childhood as a crucial period in development of overweight, the observed slower BMI development at early childhood among children of immigrants followed by a steeper increase in BMI compared with children of Swedish mothers is important for further studies and for planning of preventive public health programs.     

Gene-environment interaction between body mass index and transforming growth factor beta 1 (TGFβ1) gene in knee and hip osteoarthritis

Introduction

The objective was to investigate potential gene-environment interaction between body mass index (BMI) and each of eight TGFβ1 polymorphisms in knee and hip osteoarthritis (OA).

Methods

We conducted a case-control study of Caucasian men and women aged 45 to 86 years from Nottingham, United Kingdom (Genetics of OA and Lifestyle (GOAL) study). Cases had clinically severe symptoms and radiographic knee or hip OA; controls had no symptoms and no radiographic knee/hip OA. We used logistic regression to investigate the association of TGFβ1 polymorphisms and OA when stratifying by BMI. Knee and hip OA were analyzed separately with adjustment for potential confounders. Additive and multiplicative interactions were examined.

Results

2,048 cases (1,042 knee OA, 1,006 hip OA) and 967 controls were studied. For hip OA, the highest risk was in overweight (BMI ≥25 kg/m²) individuals with the variant allele of single-nucleotide polymorphism (SNP) rs1800468 (odds ratio (OR) 2.21, 95% confidence interval (CI) 1.55, 3.15). Evaluation of gene-environment interaction indicated significant synergetic interaction (relative excess risk due to interaction (RERI) = 0.93, synergy index (SI) = 4.33) with an attributable proportion due to interaction (AP) of 42% (AP = 0.42; 95% CI 0.16, 0.68). Multiplicative interaction was also significant (OR for interaction (ORINT) = 2.27, P = 0.015). For knee OA, the highest risk was in overweight individuals with homozygous genotype 11 of SNP rs2278422 (OR = 6.95, P <0.001). In contrast, the variant allele indicated slightly lower risks (OR = 4.72, P <0.001), a significant antagonistic interaction (RERI = -2.66, SI = 0.59), AP = -0.56 (95%CI -0.94, -0.17) and a significant multiplicative interaction (ORINT = 0.47, P = 0.013).

Conclusion

TGFβ1 gene polymorphisms interact with being overweight to influence the risk of large joint OA.     

Association of HDL-Related Loci with Age-Related Macular Degeneration and Plasma Lutein and Zeaxanthin: the Alienor Study

Background

Several genes implicated in high-density lipoprotein (HDL) metabolism have been reported to be associated with age-related macular degeneration (AMD). Furthermore, HDL transport the two carotenoids, lutein and zeaxanthin, which are highly suspected to play a key-role in the protection against AMD. The objective is to confirm the associations of HDL-related loci with AMD and to assess their associations with plasma lutein and zeaxanthin concentrations.

Methods

Alienor study is a prospective population-based study on nutrition and age-related eye diseases performed in 963 elderly residents of Bordeaux, France. AMD was graded according to the international classification, from non-mydriatic colour retinal photographs. Plasma lutein and zeaxanthin were determined by normal-phase high-performance liquid chromatography. The following polymorphisms were studied: rs493258 and rs10468017 (LIPC), rs3764261 (CETP), rs12678919 (LPL) and rs1883025 (ABCA1).

Results

After multivariate adjustment, the TT genotype of the LIPC rs493258 variant was significantly associated with a reduced risk for early and late AMD (OR=0.64, 95%CI: 0.41-0.99; p=0.049 and OR=0.26, 95%CI: 0.08-0.85; p=0.03, respectively), and with higher plasma zeaxanthin concentrations (p=0.03), while plasma lipids were not significantly different according to this SNP. Besides, the LPL variant was associated with early AMD (OR=0.67, 95%CI: 0.45-1.00; p=0.05) and both with plasma lipids and plasma lutein (p=0.047). Associations of LIPC rs10468017, CETP and ABCA1 polymorphisms with AMD did not reach statistical significance.

Conclusion

These findings suggest that LIPC and LPL genes could both modify the risk for AMD and the metabolism of lutein and zeaxanthin.