Effects of smoking and obesity on the association between CDH13 (rs3865188) and adiponectin among Korean men: the KARE study

Adiponectin is secreted exclusively by adipocytes. Adiponectin is regulated by obesity, smoking, and genetic factors, including CDH13, which may contribute to development of diseases such as cardiovascular disease. Therefore, we aim to explore the joint effect of smoking and obesity on the association between CDH13 (rs3865188) and adiponectin among Korean men. This study included 1,570 Korean men aged 40-69 years who participated in the KARE cohort study (community-based cohorts, South Korea) from 2001. Hypoadiponectinemia was defined as the lowest quartile of adiponectin. In this study, individuals with at least one at-risk allele, the T allele, had an increased risk for hypoadiponectinemia, particularly current smokers with at least one T allele together with obesity when compared to those without the T allele. In addition, individuals with the TT genotype of CDH13 rs3865188, as well as obesity, were significantly associated with a 1.8-fold (odds ratio (OR) = 9.4, 95% confidence interval (CI) = 4.4-19.6, P < 0.001) increased risk for hypoadiponectinemia compared to individuals with the TT genotype of CDH 13 rs3865188 and normal waist circumference (WC) (OR = 5.1, 95% CI = 3.5-7.6, P < 0.001). However, in the joint effect of smoking and obesity, current smokers with the TT genotype of CDH13 rs3865188, as well as obesity, were significantly associated with a 6.2-fold (OR = 24.2, 95% CI = 3.0-196.6, P < 0.001) increased risk for hypoadiponectinemia compared to nonsmokers with the TT genotype of CDH 13 rs3865188 with normal WC (OR = 3.9, 95% CI = 1.7-9.3, P < 0.001). This study suggested that the association between CDH13 and adiponectin can be modified by lifestyle factors, such as smoking and obesity, among Korean men.     

Plasma protein carbonyl levels and breast cancer risk

To study the role of oxidative stress in breast cancer risk, we analysed plasma levels of protein carbonyls in 1050 cases and 1107 controls. We found a statistically significant trend in breast cancer risk in relation to increasing quartiles of plasma protein carbonyl levels (OR = 1.2, 95% CI = 0.9-1.5; OR = 1.5, 95% CI = 1.2-2.0; OR = 1.6, 95% CI = 1.2-2.1, for the 2(nd), 3(rd) and 4(th) quartile relative to the lowest quartile, respectively, P for trend = 0.0001). The increase in risk was similar for younger (<50 years) and older women, more pronounced among women with higher physical activity levels (0.7 hrs/week for 4(th) quartile versus lowest quartile OR = 2.0, 95% CI = 1.4-3.0), higher alcohol consumption (> or = 15 grams/day for 4(th) quartile versus lowest quartile OR = 2.3, 95% CI = 1.1-4.7), and hormone replacement therapy use (HRT, OR = 2.6, 95% CI = 1.6-4.4 for 4(th) quartile versus lowest quartile). The multiplicative interaction terms were statistically significant only for physical activity and HRT. The positive association between plasma protein carbonyl levels and breast cancer risk was also observed when the analysis was restricted to women who had not received chemotherapy or radiation therapy prior to blood collection. Among controls, oxidized protein levels significantly increased with cigarette smoking and higher fruit and vegetable consumption, and decreased with alcohol consumption >30 grams per day. Women with higher levels of plasma protein carbonyl and urinary 15F(2t)-isoprostane had an 80% increase in breast cancer risk (OR = 1.8, 95% CI = 1.2-2.6) compared to women with levels below the median for both markers of oxidative stress. In summary, our results suggest that increased plasma protein carbonyl levels may be associated with breast cancer risk.     

Simple anthropometric indices in relation to cardiovascular risk factors in Chinese type 2 diabetic patients

To determine which is the best anthropometric index among body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) and waist to height ratio (WHtR) in type 2 diabetic patients, we examined the relationship between these indices and cardiovascular risk factors using partial correlation analysis, chi-square test, logistic regression analysis and Receiver Operator Characteristic (ROC) curves. Partial correlation analysis showed that among the 4 obesity indices, WHtR had the highest r values for all the cardiovascular risk factors in both sexes, followed by WC. Chi-square analysis which revealed that an increased WHtR was more strongly associated with hypertension, hypertriglyceridemia (high TG) and low high-density lipoprotein cholesterol (HDL-C) than the other indices. Logistic regression analysis showed that, after controlling for age, the hypertension, high TG and low HDL-C odds ratios of WHtR > or = 0.5 were 2.56 (95% CI: 1.24, 5.29), 2.87 (95% CI: 1.43, 5.78), 2.59 (95% CI: 1.03, 6.59) in men and 3.75 (95% CI: 1.75, 8.05), 3.21 (95% CI: 1.52, 6.79), 3.62 (95% CI: 1.43, 9.21) in women, respectively. In ROC analysis, the areas under curve of WHtR were the largest for at least one risk factor in both men and women. These results indicated that WHtR had a higher correlation with cardiovascular risk factors than WC, WHR or BMI in newly diagnosed type 2 diabetes. We proposed the measurement of WHtR as a screening tool for cardiovascular risk factors in this population.     

Prospective associations between measures of adiposity and periodontal disease

Obesity induced inflammation may promote periodontal tissue destruction and bone resorption inducing tooth loss. We examined the association between measures of adiposity and self-reported periodontal disease, using data from 36,910 healthy male participants of the Health Professionals Follow-Up Study (HPFS) who were free of periodontal disease at baseline and followed for ≤20 years (1986-2006). Self-reported height, weight, and periodontal disease data were collected at baseline, weight and periodontal disease were additionally collected on biennial follow-up questionnaires and waist and hip circumference were self-reported in 1987. These self-reported measures have been previously validated. The multivariable adjusted associations between BMI (kg/m(2)), waist circumference (WC), waist-to-hip ratio (WHR), and first report of periodontal disease diagnosis were evaluated using time-varying Cox models. We observed 2,979 new periodontal disease diagnoses during 596,561 person-years of follow-up. Significant associations and trends were observed between all measures of adiposity and periodontal disease after adjusting for age, smoking, race, dental profession, physical activity, fruit and vegetable intake, alcohol consumption, and diabetes status at baseline. BMI ≥30 kg/m(2) compared to BMI 18.5-24.9 kg/m(2) was significantly associated with greater risk of periodontal disease (hazard ratios (HR) = 1.30; 95% confidence interval (CI): 1.17-1.45). Elevated WC and WHR were significantly associated with a greater risk of periodontal disease (HR for extreme quintiles: WC = 1.27, 95% CI: 1.11-1.46; WHR = 1.34, 95% CI: 1.17-1.54). The associations of BMI and WC were significant even among nondiabetics and never smokers. Given the high prevalence of overweight, obesity, and periodontal disease this association may be of substantial public health importance.     

Associations between obesity and changes in adult BMI over time and colon cancer risk

Obesity has been associated with increased colon cancer risk in epidemiological studies; however, the specific time periods during which obesity may be most relevant as well as how changes in adult body size over time affect colon cancer risk have not been well explored. We evaluated potential associations between BMI in each age decade(20s, 30s, 40s, 50s, and 2 years before study recruitment ("recruitment period")) and in BMI changes over timeand colon cancer risk in a population-based case-control study comprising 438 cases and 491 controls. We found that obese (BMI>or=30.0 kg/m2) compared to normal (BMI>or=18.5 to <25.0 kg/m2) body size at the recruitment period was associated with increased colon cancer risk (odds ratio (OR)=1.54; 95% confidence interval (CI)=1.03-2.31; P=0.03). No associations were observed for obese body size in the other age decades. An increased risk was found for changes in BMI between the 30s decade and the recruitment period of 5-10 kg/m2 (OR=1.54; 95%CI=1.02-2.34; P=0.04) and >10 kg/m2 (OR=2.40; 95% CI=1.23-4.66; P=0.01) (P trend=0.01). Stratification by gender revealed that BMI changes>10 kg/m2 increased risk in women but not men. Similar results were found for BMI changes between the 20s decade and the recruitment period but effect sizes were smaller. Our results provide additional support to obesity's role in colon cancer and suggest large body size increases exceeding 10 kg/m2 may potentially be more important after age 30, particularly among women; however, prospective studies with sex hormone, growth factor, and pro-inflammatory biomarkers are needed to provide insights to the underlying biological mechanism(s).     

Intake of fruits and vegetables in relation to 10-year weight gain among Spanish adults

Objective: Despite the alarming increase in the prevalence of obesity, epidemiologic studies that prospectively examine the fruit and vegetable consumption and other lifestyle factors in relation to weight gain (WG) are still insufficient. We explored the associations between fruit and vegetable intake and WG over a 10‐year period in an adult Mediterranean population. Methods and Procedures: We performed a 10‐year follow‐up study with healthy participants (n = 206) aged 15–80 years at baseline in 1994, who participated in a nutrition survey in Valencia, Spain. Data on diet, lifestyle factors, and body weight were obtained in 1994 and 2004 using a food frequency questionnaire (FFQ) and direct measurements. Results: The average WG over the study period was 3.41 (s.d. 6.9) kg. In multivariate analyses, participants in the third quartile of fruit intake at baseline in 1994 had lower risk of WG ≥ 3.41 kg compared to those in the lowest quartile (oddsratio (OR) = 0.31, 95% confidence interval (CI), 0.11–0.85; P trend = 0.044). Regarding vegetable intake, the risk of WG was lowest in participants of the fourth quartile (>333 g/day), which had an 84% reduced risk of gaining 3.41 kg weight (OR = 0.18, 95% CI, 0.05–0.66; P trend = 0.017). When the intake of fruits and vegetables was combined, the risk of WG decreased across quartiles, with the lowest risk among those in the fourth quartile (OR = 0.22, 95% CI, 0.06–0.81; P trend = 0.022). Further adjustment for an increased intake of fruits and vegetables over the past 10 years reported by participants in 2004 did not appreciably alter the observed ORs. Discussion: Dietary patterns associated with a high intake of fruits and vegetables in Mediterranean populations may reduce long‐term risk of subsequent WG and obesity among adults.     

Obesity and Menstrual Irregularity: Associations With SHBG,Testosterone, and Insulin

This cross‐sectional study aimed to examine the association between different body composition measures, menstrual cycle characteristics, and hormonal factors in a population‐based sample of young women. The study sample included 726 Australian women aged 26–36 years who were not currently taking hormonal contraceptives and were not currently pregnant or breast feeding. Anthropometric measures included BMI, waist circumference (WC), and waist‐hip ratio (WHR). Menstrual cycle characteristics were self‐reported and usual cycles defined as short (≤25 days), normal (26–34 days), or long (≥35 days). Cycles were defined as irregular if there were ≥15 days between the longest and shortest cycle in the past 12 months. Fasting serum levels of sex hormone‐binding globulin (SHBG), testosterone, insulin, and glucose were measured and the free androgen index (FAI) derived. Compared with those of normal weight, obese women had at least a twofold greater odds of having an irregular cycle, whether defined by BMI (odds ratio (OR) = 2.61; 95% CI = 1.28–5.35), WC (OR 2.28; 95% CI = 1.16–4.49), or WHR (OR = 2.27; 95% CI = 1.09–4.72). Body composition measures were significantly positively associated with fasting insulin, testosterone, and FAI, and negatively associated with SHBG (P < 0.01). Fasting insulin, SHBG, and FAI had the strongest influence on the associations between obesity and irregular cycles, with statistically significant ORs of having an irregular cycle being attenuated to near null values following adjustment. In conclusion, both overall and central obesity were significantly associated with having an irregular menstrual cycle. This association was substantially influenced by hormonal factors, particularly insulin and SHBG.     

Influence of Maternal Height and Weight on Low Birth Weight: A Cross-Sectional Study in Poor Communities of Northeastern Brazil

Background

Low birth weight (LBW) is associated with an increased risk of mortality, adverse metabolic conditions, and long-term chronic morbidities. The relationship between LWB and short maternal stature coupled with nutritional status was investigated in poor communities.

Methods/Principal Findings

A cross-sectional population-based study involving 2226 mother-child pairs was conducted during the period 2009-2010 in shantytowns of Maceió, Alagoas, Brazil. Associations between LBW and maternal sociodemographics, stature and nutritional status were investigated. The outcome variable was birth weight (< 2500g and ≥ 2500g). The independent variables were the age, income, educational background, stature and nutritional status (eutrophic, underweight, overweight and obese) of the mother. The frequency of LBW was 10%. Short-statured mothers (1^st quartile of stature ≤ 152cm) showed a tendency of increased risk of LBW children compared to mothers in the 4^th quartile of stature (>160.4cm) (OR: 1.42, 95% CI: 0.96 - 1.09, p = 0.078). Children from short-statured mothers weighed an average of 125g less than those from taller mothers (3.18±0.56kg vs. 3.30±0.58kg, respectively p = 0.002). Multivariate analyses showed that short stature, age < 20y (OR: 3.05, 95% CI:1.44 - 6.47) or were underweight (OR: 2.26, 95% CI:0.92 - 5.95) increased the risk of LBW, while overweight (OR: 0.38, 95% CI:0.16 - 0.95) and obesity (OR: 0.39, 95% CI:0.11 - 1.31) had lower risk for LBW. In taller mothers, lower income and underweight were associated with LBW (OR: 1.88, 95% CI: 1.07 - 3.29 and 2.85, 95% CI:1.09 - 7.47, respectively), and obese mothers showed a trend of increased risk of LBW (OR: 1.66, 95% CI:0.84 - 3.25).

Conclusions/Significance

Overweight was found to have a protective effect in short-statured mothers, indicating that a surplus of energy may diminish the risk of LBW. Short-statured younger mothers, but not taller ones, showed higher risk of LBW. The mother being underweight, regardless of stature, was associated with LBW.     

BMI,Waist Circumference,and Mortality According to Health Status in the Older Adult Population of Spain

Among the explanations proposed for the weak and inconsistent association between BMI and mortality in the elderly are the lack of adjustment for waist circumference (WC) and that the association varies with health status. This work examines the independent association of BMI and WC with mortality in older adults, and the influence of health status on this association. A cohort of 3,536 persons representative of the Spanish population aged ≥60 years was selected in 2000 and 2001, and followed prospectively until 2007. The analyses were performed with Cox models and adjusted for the main confounders. During follow‐up, 659 persons died (18.6% of the cohort). Before adjusting for WC, mortality in the upper quartile of BMI was 15% lower than in the lower quartile (hazard ratio (HR): 0.85; 95% confidence interval (CI): 0.66–1.08; P for linear trend = 0.076). After adjusting for WC, the association was even stronger, so that mortality in the upper quartile of BMI was 37% lower than in the lower quartile (HR: 0.63; 95% CI: 0.45–0.88; P for linear trend < 0.003). Before adjusting for BMI, no association was observed between WC and mortality. After adjusting for BMI, WC was positively associated with mortality (HR for upper vs. lower quartile of WC: 1.48; 95% CI: 1.07–2.05; P for linear trend = 0.008). These associations were mainly observed in those with limitations in mobility and agility. BMI has an inverse, and WC has a direct, independent association with mortality in older adults, particularly in those with worse health status.     

Obesity and injury-related absenteeism in a population-based firefighter cohort

A consistent relationship has been demonstrated between obesity and absenteeism in the workplace. However, most studies have focused on primarily sedentary occupational groups. Firefighting is a physically demanding profession that involves significant potential for exposure to dangerous situations and strenuous work. No studies to date have evaluated the impact of obesity on risk for absenteeism among firefighters. We examined the cross-sectional association between BMI and obesity and injury-related absenteeism. BMI, body fat percentage (BF%), waist circumference (WC), injury, and injury-related absenteeism were assessed in 478 career male firefighters. One hundred and fifteen firefighters reported an injury in the previous year and the number of days absent from work due to their injury. BMI was an independent predictor of absenteeism due to injury even after adjustment for confounding variables. Firefighters meeting the definition of class II and III obesity had nearly five times (odds ratio (OR) = 4.89; 95% confidence interval (CI) = 3.63-6.58) the number missed work days due to injury when compared to their normal weight counterparts and their elevated risk was greater than firefighters with class I obesity (OR = 2.71; 95% CI = 2.01-3.65) or those who were overweight (OR = 2.55; 95% CI = 1.90-3.41). The attributable per capita costs of class II and III obesity-related absenteeism over the last year were $1,682.90 per firefighter, $254.00 per firefighter for class I obesity, and $74.41 per firefighter for overweight. Our findings suggest that class II and III obesity were associated with substantial attributable costs to employers and our cost estimates probably underestimate the actual financial burden.     

Adiposity and incident heart failure in older adults: the cardiovascular health study

While several studies have reported a positive association between overall adiposity and heart failure (HF) risk, limited and inconsistent data are available on the relation between central adiposity and incident HF in older adults. We sought to examine the association between waist circumference (WC) and incident HF and assess whether sex modifies the relation between WC and HF. Prospective study using data on 4,861 participants of the Cardiovascular Health Study (1989-2007). HF was adjudicated by a committee using information from medical records and medications. We used Cox proportional hazard models to compute hazard ratio (HR). The mean age was 73.0 years for men and 72.3 years for women; 42.5% were men and 15.3% were African Americans. WC was positively associated with an increased risk of HF: each standard deviation of WC was associated with a 14% increased risk of HF (95% CI: 3%-26%) in a multivariable model. There was not a statistically significant sex-by-WC interaction (P = 0.081). BMI was positively associated with incident HF (HR: 1.22 (95% CI: 1.15-1.29) per standard deviation increase of BMI); however, this association was attenuated and became nonstatistically significant upon additional adjustment for WC (HR: 1.09 (95% CI: 0.99-1.21)). In conclusion, a higher WC is associated with an increased risk of HF independent of BMI in community-living older men and women.     

Anthropometric risk factors for colorectal polyps in African-American women

Objective: Colorectal adenomas are thought to be precursor lesions to colorectal cancer, a leading cause of cancer incidence and mortality in African‐American women. Studies suggest that obesity is associated with risk of adenomas in white women, but little is known about the relation in African‐American women. We prospectively examined the association between selected anthropometric factors and colorectal polyps in African‐American women. Methods and Procedures: Data were obtained from the Black Women's Health Study (BWHS), a prospective cohort study of African‐American women. From 1997 to 2003, we followed 33,403 women aged ≥30 years with no prior diagnosis of cancer or polyps. Cox regression was used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for risk of polyps, with adjustment for potential confounders. Results: After 211,797 person‐years of follow‐up, 1,189 cases of colorectal polyps were reported. The IRR comparing women with a current BMI ≥35 to <25 kg/m² was 1.35 (95% CI = 1.12–1.62), after adjustment for covariates including waist‐to‐hip ratio (WHR). Women who gained ≥30 kg since age 18 were 1.76 times as likely as those who gained <5 kg to report polyps (95% CI = 1.33–2.33). The IRR comparing the highest (≥0.87) to lowest (<0.71) quintiles of WHR was 1.26 (95% CI = 1.04–1.54), after adjustment for covariates including BMI. BMI at age 18, adult height, and waist circumference (BMI‐adjusted) were not materially associated with risk. Results were similar among women with a recent endoscopy. Discussion: Weight gain and obesity in adulthood may increase the risk of colorectal polyps in African‐American women.     

The Q121 variant of ENPP1 may protect from childhood overweight/obesity in the Italian population

Ectonucleotide Pyrophosphatase Phosphodiesterase 1 (ENPP1) downregulates insulin signaling by inhibiting the insulin receptor's tyrosine-kinase. K121Q and other ENPP1 single-nucleotide polymorphisms (SNPs), IVS20delT-11 and A/G+1044TGA, have been previously associated with obesity in French children, and the risk haplotype QdelTG has also been associated with this condition in both French and German children. Our aim was to perform a case-control replication study in order to assess the possible association of childhood obesity and overweight with the above-mentioned ENPP1 SNPs, and with the QdelTG haplotype, in the Italian population. A total of 865 healthy Italian children were studied: 453 normal-weight, 243 overweight and 169 obese subjects. Genotyping was performed by Taq-Man or Light-Cycler Technology. The Q variant of K121Q showed a negative association with overweight-obesity under both additive (odds ratio (OR) = 0.74, 95% confidence interval (CI) = 0.57-0.97, P = 0.030) and recessive (OR = 0.32, 95% CI = 0.10-0.97, P = 0.035) modes of inheritance. The Z-score of BMI showed a significant decreasing trend from children K/K homozygous to K/Q heterozygous, and to Q/Q homozygous (0.45 vs. 0.28 vs. -0.19; P = 0.009), according to the additive model. The two other SNPs and the QdelTG haplotype did not exhibit any association with overweight/obesity. This is the first child-based study showing a protective role of the 121Q variant of ENPP1 against overweight/obesity.     

Obesity in 70‐Year‐Old Subjects as a Risk Factor for 15‐Year Coronary Heart Disease Incidence

Objective: To investigate the role of obesity in general and waist circumference (WC) and BMI in particular as risk factors for 15‐year incidence of coronary heart disease (CHD) in the elderly. Research Methods and Procedures: This prospective study was based on 1597 (737 males and 860 females) 70‐year‐olds free from CHD and participants of three birth cohorts examined in 1971 to 1972 (Cohort I), 1976 to 1977 (Cohort II), and 1981 to 1982 (Cohort III) at Göteborg, Sweden. Fifteen‐year incidence of CHD (fatal and nonfatal) was ascertained from follow‐up examinations and registers. Relative risk (RR) for first ever CHD in reference to the lowest quartiles of WC and BMI was calculated from Cox regression. Results: In males, RRs for CHD in the highest WC and BMI quartiles were 1.36 [95% confidence interval (CI) 1.00 to 1.85] and 1.42 (95% CI 1.04 to 1.92), respectively, after adjustment for cohorts, smoking habits, diabetes, systolic blood pressure, and total cholesterol. In men, the risk associated with WC was independent of BMI. Neither WC nor BMI was related to CHD risk in females. After exclusion of first 5‐year all‐cause deaths, the adjusted RRs in the highest WC and BMI quartiles in males were 1.47 (95% CI 1.06 to 2.04) and 1.42 (1.04 to 1.92), respectively. In females, a significantly higher RR of 1.41 (95% CI 1.02 to 1.94) was observed in the second BMI quartile only after such exclusions. Discussion: WC, an indicator of both central and general obesity, appears to be a stronger predictor of CHD than BMI in elderly males, but in females, obesity was not a risk factor for CHD.     

Prospective Study of Optimal Obesity Index Cut-Off Values for Predicting Incidence of Hypertension in 18–65-Year-Old Chinese Adults

Background

Overweight and obesity increase the risk of elevated blood pressure; most of the studies that serve as a background for the debates on the optimal obesity index cut-off values used cross-sectional samples. The aim of this study was to determine the cut-off values of anthropometric markers for detecting hypertension in Chinese adults with data from prospective cohort.

Methods

This study determines the best cut-off values for the obesity indices that represent elevated incidence of hypertension in 18–65-year-old Chinese adults using data from the China Health and Nutrition Survey (CHNS) 2006–2011 prospective cohort. Individual body mass index (BMI), waist circumference (WC), waist:hip ratio (WHR) and waist:stature ratio (WSR) were assessed. ROC curves for these obesity indices were plotted to estimate and compare the usefulness of these obesity indices and the corresponding values for the maximum of the Youden indices were considered the optimal cut-off values.

Results

Five-year cumulative incidences of hypertension were 21.5% (95% CI: 19.4–23.6) in men and 16.5% (95% CI: 14.7–18.2) in women, and there was a significant trend of increased incidence of hypertension with an increase in BMI, WC, WHR or WSR (P for trend < 0.001) in both men and women. The Youden index indicated that the optimal BMI, WC, WHR, WSR cut-off values were 23.53 kg/m², 83.7 cm, 0.90, and 0.51 among men. The optimal BMI, WC, WHR, WSR cut-off values were 24.25 kg/m², 79.9 cm, 0.85 and 0.52 among women.

Conclusions

Our study supported the hypothesis that the cut-off values for BMI and WC that were recently developed by the Working Group on Obesity in China (WGOC), the cut-off values for WHR that were developed by the World Health Organization (WHO), and a global WSR cut-off value of 0.50 may be the appropriate upper limits for Chinese adults.     

Association analysis of the FTO gene with obesity in children of Caucasian and African ancestry reveals a common tagging SNP

Recently an association was demonstrated between the single nucleotide polymorphism (SNP), rs9939609, within the FTO locus and obesity as a consequence of a genome wide association (GWA) study of type 2 diabetes in adults. We examined the effects of two perfect surrogates for this SNP plus 11 other SNPs at this locus with respect to our childhood obesity cohort, consisting of both Caucasians and African Americans (AA). Utilizing data from our ongoing GWA study in our cohort of 418 Caucasian obese children (BMI>or=95th percentile), 2,270 Caucasian controls (BMI<95th percentile), 578 AA obese children and 1,424 AA controls, we investigated the association of the previously reported variation at the FTO locus with the childhood form of this disease in both ethnicities. The minor allele frequencies (MAF) of rs8050136 and rs3751812 (perfect surrogates for rs9939609 i.e. both r(2) = 1) in the Caucasian cases were 0.448 and 0.443 respectively while they were 0.391 and 0.386 in Caucasian controls respectively, yielding for both an odds ratio (OR) of 1.27 (95% CI 1.08-1.47; P = 0.0022). Furthermore, the MAFs of rs8050136 and rs3751812 in the AA cases were 0.449 and 0.115 respectively while they were 0.436 and 0.090 in AA controls respectively, yielding an OR of 1.05 (95% CI 0.91-1.21; P = 0.49) and of 1.31 (95% CI 1.050-1.643; P = 0.017) respectively. Investigating all 13 SNPs present on the Illumina HumanHap550 BeadChip in this region of linkage disequilibrium, rs3751812 was the only SNP conferring significant risk in AA. We have therefore replicated and refined the association in an AA cohort and distilled a tag-SNP, rs3751812, which captures the ancestral origin of the actual mutation. As such, variants in the FTO gene confer a similar magnitude of risk of obesity to children as to their adult counterparts and appear to have a global impact.     

Association of PPARG2 Pro12Ala variant with larger body mass index in Mestizo and Amerindian populations of Mexico

Previous studies have sought to associate the Pro12Ala variant of the peroxisome proliferator-activated receptor gamma2 (PPARG2) gene with type 2 diabetes, insulin resistance, and obesity, with controversial results. We have determined the Pro12Ala variant frequency in 370 nondiabetic Mexican Mestizo subjects and in five Mexican Amerindian groups and have investigated its possible association with lipid metabolism, insulin serum levels, and obesity in three of these populations. Two independent case-control studies were conducted in 239 nondiabetic individuals: 135 case subjects (BMI > or = 25 kg/m2) and 104 control subjects (BMI < 25 kg/m2). The PPARG2 Ala12 allele frequency was higher in most Amerindian populations (0.17 in Yaquis, 0.16 in Mazahuas, 0.16 in Mayans, and 0.20 in Triquis) than in Asians, African Americans, and Caucasians. The Pro12Ala and Ala12Ala (X12Ala) genotypes were significantly associated with greater BMI in Mexican Mestizos and in two Amerindian groups. X12Ala individuals had a higher risk of overweight or obesity than noncarriers in Mestizos (OR = 3.67; 95% CI, 1.42-9.48; p = 0.007) and in Yaquis plus Mazahuas (OR = 3.21; 95% CI, 1.27-8.11; p = 0.013). Our results provide further support of the association between the PPARG2 Ala12 allele and risk of overweight or obesity in Mestizos and two Amerindian populations from Mexico.     

Modification by N-acetyltransferase 1 genotype on the association between dietary heterocyclic amines and colon cancer in a multiethnic study

OBJECTIVE: Colorectal cancer incidence is greater among African Americans, compared to whites in the U.S., and may be due in part to differences in diet, genetic variation at metabolic loci, and/or the joint effect of diet and genetic susceptibility. We examined whether our previously reported associations between meat-derived heterocyclic amine (HCA) intake and colon cancer were modified by N-acetyltransferase 1 (NAT1) or 2 (NAT2) genotypes and whether there were differences by race. METHODS: In a population-based, case-control study of colon cancer, exposure to HCAs was assessed using a food-frequency questionnaire with a meat-cooking and doneness module, among African Americans (217 cases and 315 controls) and whites (290 cases and 534 controls). RESULTS: There was no association with NAT1*10 versus NAT1-non*10 genotypes for colon cancer. Among whites, there was a positive association for NAT2-"rapid/intermediate" genotype [odds ratio (OR)=1.4; 95% confidence interval (CI)=1.0, 1.8], compared to the NAT2-"slow" that was not observed among African Americans. Colon cancer associations with HCA intake were modified by NAT1, but not NAT2, regardless of race. However, the "at-risk" NAT1 genotype differed by race. For example, among African Americans, the positive association with 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) was confined to those with NAT1*10 genotype (OR=1.8; 95% CI=1.0, 3.3; P for interaction=0.02, comparing highest to lowest intake), but among whites, an association with 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was confined to those with NAT1-non*10 genotype (OR=1.9; 95% CI=1.1, 3.1; P for interaction=0.03). CONCLUSIONS: Our data indicate modification by NAT1 for HCA and colon cancer associations, regardless of race. Although the at-risk NAT1 genotype differs by race, the magnitude of the individual HCA-related associations in both race groups are similar. Therefore, our data do not support the hypothesis that NAT1 by HCA interactions contribute to differences in colorectal cancer incidence between African Americans and whites.     

Association between BMI and metabolic syndrome and adenomatous colonic polyps in Korean men

Obesity and insulin resistance are associated with the risk of colon cancer. Adenomatous colonic polyps are precancerous lesions of colon cancer. We investigated whether BMI and the metabolic syndrome are associated with the presence of adenomatous colonic polyps in Korean men. Anthropometric measurements, metabolic risk factors, and colonoscopic pathologic findings were assessed in 1,898 men who underwent routine colonoscopy at the Health Promotion Center of Asan Medical Center in 2005. The modified National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) and International Diabetes Federation (IDF) criteria were used for the definition of the metabolic syndrome. Multiple logistic regression analysis was used to evaluate the association between BMI and the metabolic syndrome and adenomatous polyps. Compared with men in the 1st quintile of the BMI, the adjusted odds ratio (OR) and 95% confidence interval (CI) for adenomatous polyps in men in the 2nd, 3rd, 4th, and 5th quintiles of the BMI were 1.55 (1.10-2.19), 1.57 (1.10-2.24), 1.94 (1.34-2.81), and 1.99 (1.31-3.01), respectively (P for trend <0.0001). Men with triglycerides (TGs) > or = 150 mg/dl were significantly more likely to have adenomatous polyps than were men with TG <150 mg/dl (OR 1.29; 95% CI 1.03-1.62). As a function of the number of metabolic risk factors, the ORs for adenomatous polyps were 1.41 (1.03-1.93), 1.52 (1.08-2.12), 1.46 (1.01-2.12), and 1.77 (1.08-2.90) for 1, 2, 3, and > or = 4 risk factors, respectively (P for trend <0.05). Adenomatous colonic polyps were significantly associated with increased BMI levels. Subjects with even one component of the metabolic syndrome had a significantly higher risk for developing adenomatous polyps compared to those subjects without any component in Korean men.