Abstract
BackgroundGene-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 FindingsWe 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/m2) and 373 non-obese controls (BMI 18.5 to <24 kg/m2) 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 SignificanceThese 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.
Highlights
It has been argued that gene-gene interaction is a ubiquitous component of the genetic architecture of common human diseases, such as obesity [1]
These results suggest that the single nucleotide polymorphisms (SNPs) from the renin-angiotensin system (RAS)-related genes may contribute to the risk of obesity in an interactive manner in a Chinese population
The aim of our study was to explore the contribution of epistasis among RAS related genes, including AGT, angiotensin converting enzyme (ACE), ATR1, MAS1, nitric oxide synthase 3 (NOS3) and bradykinin receptor 2 (BDKRB2) genes
Summary
It has been argued that gene-gene interaction is a ubiquitous component of the genetic architecture of common human diseases, such as obesity [1]. The complexity of obesity may be explained in part by complex genegene interaction or epistasis [8,9,10]. The consistent differences in these estimates suggest that as much as one third of the heritable variance may be due to non-additive genetic variance, including allelic (dominance and recessivity) and non-allelic gene interactions. Describing gene-gene interactions is imperative to characterizing certain obesity-related traits, when each involved locus only demonstrates a minor marginal effect. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
