Potential Interactions Between Genetic Polymorphisms of the Transforming Growth Factor-beta Pathway and Environmental Factors in Abdominal Aortic Aneurysms

Objective/Background: Evidence has accumulated that multiple polymorphisnns in the transforming growth factor (TGF)-beta pathway and renin angiotensin system play important roles in determining susceptibility to abdominal aortic aneurysm (AAA). Few studies have considered interactions between these gene polymorphisms and environmental factors. The aim of this study was to evaluate the contribution of single nucleotide polymorphisnns (SNPs) and complex gene environment interactions in AAA. Methods: Six SNPs located in TGFB, TGFBR1, TGFBR2 and AGTR1 were selected. Genotyping of blood samples and collection of lifestyle factors were performed in 155 unrelated participants with AAAs and 310 non-AAA controls. Unconditional logistic regression was performed to assess the effects of SNPs on the risk of AAA. Generalized multifactor dimensionality reduction (GMDR) was used to evaluate gene gene and gene environment interactions. Results: Participants carrying TGFB1 rs1800469 IT (odds ratio [OR] 1.83, 95% confidence interval [Cl] 1.18-2.85) or AGTR1 rs12695895 TT (OR 4.21, 95% Cl 1.41-12.53) genotypes had a higher risk of AAA than those with the common CC genotype. The gene gene interaction of AGTR1 rs5182, TGFBR1 rs1626340, and TGFB1 rs1800469 was found to be the best model according to the results of the GMDR analysis (cross validation consistency [CVC]) 10/10; p = .010). Smoking, dyslipidemia, and rs1800469 together contributed to the risk of AAA, which demonstrated a potential and complex gene environment interaction among the three variants that might affect AAA risk (CVC 6/10; p = .001). Conclusion: In this study of the Chinese population, homozygosity of TGFB1 rs1800469-T and AGTR1 rs12695895-T might be associated with increased risk of AAA. The complex gene gene and gene environment interactions. might contribute to the risk of AAA. As a small study, the preliminary results need extensive validation and replication in larger populations. (C) 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.National Natural Science Foundation of China [81230066]; Health Care Foundation of PLA [09BJZ04]SCI(E)PubMedARTICLEyhhu@bjmu.edu.cn; pla301dml@vip.sina.com171-775