Dataset Information

Novel abdominal adiposity genes and the risk of type 2 diabetes: findings from two prospective cohorts.

ABSTRACT: Three loci were recently identified for central adiposity from a genome wide association study (MSRA [rs545854; G/C], LYPLAL1 [rs2605100; G/A], TFAP2B [rs987237; A/G]). Central obesity is a strong risk factor for type 2 diabetes (T2D). Therefore, we hypothesized that these single nucleotide polymorphisms (SNPs) would be associated with increased risk of T2D and may influence circulating adipokine concentrations. Participants from two large case control studies nested in the Nurses' Health Study (3394 women, 1245 cases) and the Health Professionals Follow-up Study (2154 men, 862 cases) were genotyped for these SNPs. The association of these SNPs with plasma adipokine concentrations was determined among a subgroup of women without diabetes (n=987). After adjustment for age and other risk factors of diabetes, the MSRA variant was associated with an increased T2D risk in men only, with an adjusted OR of 1.30 (95% CI: 1.09-1.56) associated with each copy of the variant allele. In pooled analyses of men and women, each additional copy of the LYPLAL1 allele (G) was associated with 9% increased T2D risk (adjusted OR 1.09; 95%CI: 0.99-1.19). No significant associations were seen with the TFAP2B SNP with a pooled adjusted OR of 1.05 (95% CI: 0.95-1.17) per allele copy. In addition, carriers of the MSRA risk variant had lower percent high molecular weight adiponectin (-2.1%, p=0.04). Carriers of the TFAP2B risk variant, however, had lower leptin levels (-2.7 ng/ml, p=0.005). These findings suggest potential associations of novel central obesity genes with T2D risk and adipokine regulation.

SUBMITTER: Yeung E

PROVIDER: S-EPMC3110388 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Novel abdominal adiposity genes and the risk of type 2 diabetes: findings from two prospective cohorts.

Yeung Edwina E Qi Lu L Hu Frank B FB Zhang Cuilin C

International journal of molecular epidemiology and genetics 20110415 2

Three loci were recently identified for central adiposity from a genome wide association study (MSRA [rs545854; G/C], LYPLAL1 [rs2605100; G/A], TFAP2B [rs987237; A/G]). Central obesity is a strong risk factor for type 2 diabetes (T2D). Therefore, we hypothesized that these single nucleotide polymorphisms (SNPs) would be associated with increased risk of T2D and may influence circulating adipokine concentrations. Participants from two large case control studies nested in the Nurses' Health Study ...[more]

PMID: 21686128

Similar Datasets

Project description:Background & aimsObesity in adulthood has been associated with increased risk of liver-related mortality. Whether higher levels of physical activity counteract the excess risk conferred by obesity remains unknown. We simultaneously evaluated the long-term impact of physical activity and adiposity on liver-related mortality, within 2 nationwide populations.MethodsWe conducted a prospective cohort study of 77,238 women and 48,026 men, with detailed, validated assessments of weekly physical activity (metabolic equivalent task [MET]-hours]), adiposity (body mass index [BMI], waist circumference), and diet, alcohol use and clinical comorbidities, biennially from 1986 through 2012. Using Cox proportional hazards regression models, we calculated multivariable-adjusted hazard ratios (aHRs) and 95% CIs for liver-related mortality, including death from hepatocellular carcinoma (HCC) and other complications of cirrhosis.ResultsOver 1,856,226 person-years, we recorded 295 liver-related deaths (108 HCC; 187 cirrhosis). Risk of liver-related mortality increased monotonically with higher BMI during adulthood (ptrend<0.0001) and with weight gain during early adulthood (ptrend <0.0001). The risk of liver-related mortality also declined progressively, with increasing physical activity (ptrend = 0.0003); the aHRs across increasing physical activity quintiles were: 1.0, 0.70 (95% CI 0.51-0.96), 0.59 (95% CI 0.42-0.84), 0.52 (95% CI 0.36-0.74) and 0.46 (95% CI 0.31-0.66). Compared to lean-active adults (BMI <25; ≥18 MET-hours/week), the aHRs for obese-active, lean-sedentary, and obese-sedentary adults were: 1.04 (95% CI 0.73-1.37), 2.08 (95% CI 1.21-3.33) and 3.40 (95% CI 2.06-5.56), respectively. Findings were similar for HCC-specific and cirrhosis-specific mortality. Overall, engaging in average-pace walking for >3 hours/week could have prevented 25% of liver-related deaths (95% CI 0.12-0.38).ConclusionsIn 2 prospective, nationwide cohorts, both excess adiposity and reduced physical activity were significant predictors of liver-related mortality. Achieving higher physical activity levels counteracted the excess liver-related risks associated with obesity.Lay summaryThis is the first large, prospective cohort study to simultaneously evaluate the impact of obesity and physical activity on the long-term risk of liver-related mortality in 2 nationwide populations of American men and women. The study demonstrated that obesity predicted significantly increased risk of liver-related mortality, while physical activity predicted significantly lower risk of liver-related mortality. Importantly, the excess risk of liver-related mortality observed with obesity was no longer statistically significant among adults who engaged in the equivalent of average-pace walking for 3 hours or more, per week.

Project description:BackgroundIt is well established that aerobic physical activity can lower the risk of type 2 diabetes (T2D), but whether muscle-strengthening activities are beneficial for the prevention of T2D is unclear. This study examined the association of muscle-strengthening activities with the risk of T2D in women.Methods and findingsWe prospectively followed up 99,316 middle-aged and older women for 8 years from the Nurses' Health Study ([NHS] aged 53-81 years, 2000-2008) and Nurses' Health Study II ([NHSII] aged 36-55 years, 2001-2009), who were free of diabetes, cancer, and cardiovascular diseases at baseline. Participants reported weekly time spent on resistance exercise, lower intensity muscular conditioning exercises (yoga, stretching, toning), and aerobic moderate and vigorous physical activity (MVPA) at baseline and in 2004/2005. Cox regression with adjustment for major determinants for T2D was carried out to examine the influence of these types of activities on T2D risk. During 705,869 person years of follow-up, 3,491 incident T2D cases were documented. In multivariable adjusted models including aerobic MVPA, the pooled relative risk (RR) for T2D for women performing 1-29, 30-59, 60-150, and >150 min/week of total muscle-strengthening and conditioning activities was 0.83, 0.93, 0.75, and 0.60 compared to women reporting no muscle-strengthening and conditioning activities (p<0.001 for trend). Furthermore, resistance exercise and lower intensity muscular conditioning exercises were each independently associated with lower risk of T2D in pooled analyses. Women who engaged in at least 150 min/week of aerobic MVPA and at least 60 min/week of muscle-strengthening activities had substantial risk reduction compared with inactive women (pooled RR = 0.33 [95% CI 0.29-0.38]). Limitations to the study include that muscle-strengthening and conditioning activity and other types of physical activity were assessed by a self-administered questionnaire and that the study population consisted of registered nurses with mostly European ancestry.ConclusionsOur study suggests that engagement in muscle-strengthening and conditioning activities (resistance exercise, yoga, stretching, toning) is associated with a lower risk of T2D. Engagement in both aerobic MVPA and muscle-strengthening type activity is associated with a substantial reduction in the risk of T2D in middle-aged and older women.

Project description:To examine the relations between genetic loci, plasma lipoprotein(a) [Lp(a)] levels, and cardiovascular disease (CVD) risk among diabetic patients and compare with the observations in the general population.In two prospective cohorts of patients with type 2 diabetes (n= 2308) from the Nurses' Health Study and the Health Professional Follow-Up Study, we performed (i) genome-wide association (GWA) scans for plasma Lp(a); (ii) prospective analysis of plasma Lp(a) for CVD risk and mortality; and (iii) genetic association analysis for CVD risk and mortality. Meta-analysis of the two GWA scans yielded 71 single-nucleotide polymorphisms (SNPs) on chromosome 6q associated with plasma Lp(a) levels at a genome-wide significance level (P< 5 × 10(-8)). The SNP rs10455872 in LPA was most strongly associated with Lp(a) (P= 4.60 × 10(-39)). Forward-selection analysis indicated that rs10455872 and other five SNPs in a region encompassing LPA, PLG, SLC22A3, and LPAL2 genes were independently associated with Lp(a) levels and jointly explained ?20% of variation in diabetic patients. In prospective analysis, we did not find any significant association between plasma levels and CVD incidence; the relative risk for coronary heart disease (CHD), CVD, and CVD death was 1.05 [95% confidence interval (CI): 0.95-1.15], 1.05 (0.96-1.15), and 1.21 (0.99-1.47) per 1-SD higher log-transformed Lp(a) levels, respectively. Consistently, none of the Lp(a) SNPs were associated with CVD risk or mortality (all P> 0.09). For the best SNP rs10455872 for plasma Lp(a) levels, the OR for CHD, CVD, and CVD death was 0.94 (95% CI: 0.69-1.28), 0.97 (0.72-1.29), and 1.23 (0.79-1.92), respectively. The genetic effect on CHD risk showed a significant heterogeneity between the diabetic and the general populations (P= 0.006).Our data indicate that the effect of Lp(a) on CVD risk among diabetic patients might be different from that in the general population. Diabetes status may attenuate the relation between Lp(a) and cardiovascular risk.

Dataset Information

Novel abdominal adiposity genes and the risk of type 2 diabetes: findings from two prospective cohorts.

Publications

Novel abdominal adiposity genes and the risk of type 2 diabetes: findings from two prospective cohorts.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets