Dataset Information

Contributions of renin-angiotensin system-related gene interactions to obesity in a Chinese population.

ABSTRACT:

Background

Gene-gene interactions may be partly responsible for complex traits such as obesity. Increasing evidence suggests that the renin-angiotensin system (RAS) contributes to the etiology of obesity. How the epistasis of genes in the RAS contributes to obesity is still under research. We aim to evaluate the contribution of RAS-related gene interactions to a predisposition of obesity in a Chinese population.

Methodology and principal findings

We selected six single nucleotide polymorphisms (SNPs) located in angiotensin (AGT), angiotensin converting enzyme (ACE), angiotensin type 1 receptor (AGTR1), MAS1, nitric oxide synthase 3 (NOS3) and the bradykinin B2 receptor gene (BDKRB2), and genotyped them in 324 unrelated individuals with obesity (BMI ? 28 kg/m(2)) and 373 non-obese controls (BMI 18.5 to <24 kg/m(2)) from a large scale population-based cohort. We analyzed gene-gene interactions among 6 polymorphic loci using the Generalized Multifactor Dimensionality Reduction (GMDR) method, which has been shown to be effective for detecting gene-gene interactions in case-control studies with relatively small samples. Then we used logistic regression models to confirm the best combination of loci identified in the GMDR. It showed a significant gene-gene interaction between the rs220721 polymorphism in the MAS1 gene and the rs1799722 polymorphism in the gene BDKB2R. The best two-locus combination scored 9 for cross-validation consistency and 9 for sign test (p = 0.0107). This interaction showed the maximum consistency and minimum prediction error among all gene-gene interaction models evaluated. Moreover, the combination of the MAS1 rs220721 and the BDKRB2 rs1799722 was associated with a significantly increased risk of obesity (OR 1.82, CI 95%: 1.15-2.88, p = 0.0103).

Conclusions and significance

These results suggest that the SNPs from the RAS-related genes may contribute to the risk of obesity in an interactive manner in a Chinese population. The gene-gene interaction may serve as a novel area for obesity research.

SUBMITTER: Zhou JB

PROVIDER: S-EPMC3412812 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Contributions of renin-angiotensin system-related gene interactions to obesity in a Chinese population.

Zhou Jian-Bo JB Liu Chang C Niu Wen-Yan WY Xin Zhong Z Yu Mei M Feng Jian-Ping JP Yang Jin-Kui JK

PloS one 20120806 8

<h4>Background</h4>Gene-gene interactions may be partly responsible for complex traits such as obesity. Increasing evidence suggests that the renin-angiotensin system (RAS) contributes to the etiology of obesity. How the epistasis of genes in the RAS contributes to obesity is still under research. We aim to evaluate the contribution of RAS-related gene interactions to a predisposition of obesity in a Chinese population.<h4>Methodology and principal findings</h4>We selected six single nucleotide ...[more]

PMID: 22880127

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Project description:BackgroundThe Dietary Approaches to Stop Hypertension (DASH) diet is widely recommended to lower blood pressure, but its mechanisms of action are unclear. Lines of evidence suggest an interaction with the renin-angiotensin-aldosterone system (RAAS).ObjectiveWe conducted a randomized, controlled, cross-over feeding trial to test RAAS-related mechanisms underlying the DASH diet in patients with isolated systolic hypertension.MethodsParticipants entered a 1-wk run-in period on a control (CON) diet and then consumed the DASH or CON diets for 4 wk each in randomized sequence. Calorie content was controlled to maintain weight, and sodium intake was set at 3 g daily. After each diet, participants had hormonal and hemodynamic assessments obtained at baseline, in response to RAAS inhibition with captopril (CAP) 25 mg, and to graded angiotensin II (AngII) infusions (1 ng/kg and 3 ng/kg × 45 min). Primary outcomes were mean arterial pressure (MAP) and renal blood flow (RBF), and secondary outcomes were diastolic function, pulse wave velocity (PWV), plasma renin activity (PRA), and aldosterone (ALDO) responses by diet.ResultsIn total, 44 (19 female) participants completed the study. DASH + CAP significantly lowered MAP compared with CON + CAP (83 ± 11 mmHg compared with 88 ± 14 mmHg, P <0.01). RBF was increased with DASH + CAP compared with CON + CAP (486 ± 149 cc/min compared with 451 ± 171 cc/min, P <0.001). Study diet did not change PWV but CAP reduced diastolic function on the DASH diet (P <0.05). DASH + CAP significantly increased PRA compared with CON + CAP (1.52 ± 1.78 ng/mL/min compared with 0.89 ± 1.17 ng/mL/min; P <0.001). ALDO sensitivity to AngII infusion was greater with DASH when compared to CON (17.4 ± 7.7 ng/mL compared with 13.8 ± 6.2 ng/dL, P <0.05) as was DASH + CAP compared with CON + CAP (15.1 ± 5.3 ng/dL compared with 13.1 ± 5.9 ng/mL, P <0.05).ConclusionsThe DASH diet interacts with the RAAS resulting in vascular and hormonal responses similar to a natriuretic effect, which appears to augment the hypotensive effect of angiotensin-converting enzyme (ACE) inhibition in individuals with isolated systolic hypertension. This trial was registered at clinicaltrials.gov as NCT00123006.

Dataset Information

Contributions of renin-angiotensin system-related gene interactions to obesity in a Chinese population.

Background

Methodology and principal findings

Conclusions and significance

Publications

Contributions of renin-angiotensin system-related gene interactions to obesity in a Chinese population.

Similar Datasets

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