Dataset Information

Adiposity significantly modifies genetic risk for dyslipidemia.

ABSTRACT: Recent genome-wide association studies have identified multiple loci robustly associated with plasma lipids, which also contribute to extreme lipid phenotypes. However, these common genetic variants explain <12% of variation in lipid traits. Adiposity is also an important determinant of plasma lipoproteins, particularly plasma TGs and HDL cholesterol (HDLc) concentrations. Thus, interactions between genes and clinical phenotypes may contribute to this unexplained heritability. We have applied a weighted genetic risk score (GRS) for both plasma TGs and HDLc in two large cohorts at the extremes of BMI. Both BMI and GRS were strongly associated with these lipid traits. A significant interaction between obese/lean status and GRS was noted for each of TG (P(Interaction) = 2.87 × 10(-4)) and HDLc (P(Interaction) = 1.05 × 10(-3)). These interactions were largely driven by SNPs tagging APOA5, glucokinase receptor (GCKR), and LPL for TG, and cholesteryl ester transfer protein (CETP), GalNAc-transferase (GALNT2), endothelial lipase (LIPG), and phospholipid transfer protein (PLTP) for HDLc. In contrast, the GRSLDL cholesterol × adiposity interaction was not significant. Sexual dimorphism was evident for the GRSHDL on HDLc in obese (P(Interaction) = 0.016) but not lean subjects. SNP by BMI interactions may provide biological insight into specific genetic associations and missing heritability.

SUBMITTER: Cole CB

PROVIDER: S-EPMC4617143 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Adiposity significantly modifies genetic risk for dyslipidemia.

Cole Christopher B CB Nikpay Majid M Lau Paulina P Stewart Alexandre F R AF Davies Robert W RW Wells George A GA Dent Robert R McPherson Ruth R

Journal of lipid research 20140915 11

Recent genome-wide association studies have identified multiple loci robustly associated with plasma lipids, which also contribute to extreme lipid phenotypes. However, these common genetic variants explain <12% of variation in lipid traits. Adiposity is also an important determinant of plasma lipoproteins, particularly plasma TGs and HDL cholesterol (HDLc) concentrations. Thus, interactions between genes and clinical phenotypes may contribute to this unexplained heritability. We have applied a ...[more]

PMID: 25225679

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Project description:BACKGROUND:Hyperuricemia predisposes to gout, which may result in tophi, kidney stones, or urate nephropathy even kidney failure. Many metabolic risk factors and disorders has been recognized as a key risk factor contributing to development of hyperuricemia. AIM:To determine the prevalence of hyperuricemia and its association with adiposity and dyslipidemia. METHODS:We recruited non-hospitalized participants (aged ?35?years) in Xinjiang, a northwest part of China based on the Cardiovascular Risk Survey (CRS 2008-2012). Information of general health status, seafood or internal organs intake and history of disease were obtained by using an interview-based questionnaire. The levels of serum uric acid (sUA) and creatinine and lipid profiles were measured. A multivariate logistic regression model was performed to assess the association between prevalence of hyperuricemia and adiposity and dyslipidemia. RESULTS:This study recruited 16,611 participants, and 14,618 was included (mean age of 50.5?±?12.6?years, 46.6% was males). The study population comprised three ethnic groups with 39.4% of Han, 32.6% of Uygur and 28% of Kazakh Chinese. The overall prevalence of hyperuricemia was 9.1% (95% CI: 8.6 to 9.6) and it was11.8% in men was 6.7% in women. The three ethnic groups also had different hyperuricemia prevalence with 15.4% in Han, 4.6% in Uygur and 5.5% in Kazakh Chinese, which corresponding to a respective mean sUA levels of 306.2?±?86.9, 249.4?±?76.1 and 259.8?±?78.7??mol/L. Participants with diabetes, hypertension or hypertriglyceridemia and higher blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC) had higher levels of sUA (P?<?0.001 respectively). Multivariate logistic regression analysis revealed that age, gender, ethnicity, drinking, obesity, waist circumference, TG (?2.26?mmol/L), TC (?6.22?mmol/L) are major risk factors for hyperuricemia. Compared to the 35-44-year age group [adjusted odds ratio (AOR)?=?1], the risk of hyperuricemia increased 1.61-fold in the 65-74-year age group (AOR?=?1.61, 95% CI: 1.34-1.91; P?<?0.001), and 1.71-fold in the 75- and older age group (AOR?=?1.71, 95% CI: 1.27-2.29; P?<?0.001). There was a 1.45-fold higher risk of hyperuricemia in men (AOR?=?1.45, 95% CI: 1.24-1.68; P?<?0.001) compared to women. Further, the risk of hyperuricemia increased significantly with drinking (AOR?=?1.36; 95% CI: 1.16-1.61; P?<?0.001), overweight (AOR?=?1.25; 95% CI: 1.06-1.48; P?=?0.01), obesity (AOR?=?1.28; 95% CI: 1.10-1.49; P?<?0.001), waist circumference (AOR?=?1.48; 95% CI: 1.24-1.78; P?<?0.001), TC (?6.22?mmol/L, AOR?=?1.45; 95% CI: 1.19-1.75; P?<?0.001), TG (?2.26?mmol/L, AOR?=?2.74; 95% CI: 2.39-3.14; P?<?0.001). CONCLUSIONS:These findings documented that the hyperuricemia is prevalent in the economically developing regions of northwest China. Hyperuricemia is associated with advanced age, male ender and general metabolic and cardiovascular risk factors. Obesity and dyslipidemia increase the risk of hyperuricemia.

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Adiposity significantly modifies genetic risk for dyslipidemia.

Publications

Adiposity significantly modifies genetic risk for dyslipidemia.

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