Gene-Gene Interactions in Renin-Angiotensin-Aldosterone System Contributes to End-Stage Renal Disease Susceptibility in a Han Chinese Population

Abstract

Objective. In this study, we investigated whether RAAS gene single nucleotide polymorphisms (SNPs) and their interactions were associated with end-stage renal stage (ESRD). Methodology and Results. This was a case-control study for 647 ESRD cases and 644 controls. AGT (M235T (rs699) and T174M (rs4762)), AGTR1 (A1166C (rs5186) and C573T (rs5182)), ACE (I/D (rs1799752) and G2350A (rs4343)), and CYP11B2 C-344T (rs1799998) were genotyped and compared between cases and controls to identify SNPs associated with ESRD susceptibility. Multifactor dimensionality reduction (MDR) was used to identify gene-gene interactions. Several RAAS genes were associated with ESRD: AGT M235T, ACE I/D, ACE G2350A, and CYP11B2 C-344T. By MDR analysis, a three-locus model (ACE ID/ACE G2350A/CYP11B2 C-344T) of gene-gene interaction was the best for predicting ESRD risk, and its maximum testing accuracy was 56.08% and maximum cross-validation consistency was 9/10. ESRD risk was higher with the simultaneous occurrence of ACE I/D DD-ACE G2350A AA. AGT, ACE, and CYP11B2 gene polymorphisms are associated with ESRD. Conclusions. The gene-gene interaction effects of ACE I/D, ACE G2350A, and CYP11B2 C-344T polymorphisms are more important than individual factors for ESRD development among Han Chinese.

Angiotensinogen (AGT) gene missense polymorphisms (rs699 and rs4762) and diabetic nephropathy in Caucasians with type 2 diabetes mellitus

“…In certain populations, the association between increased risk of DN and the polymorphic allele T or genotype TT was demonstrated (i.e., in two Indian populations [23,24], a Pakistani [25], Tunisian [26], Taiwanese [27], Japanese [28], Chinese [29], and Turkish population [30]). However, the reviews and extensive meta-analyses could not confirm the association of rs699 with DN [13,14,31,32]. Our results match these findings as we found no association between rs699 and DN in the T2DM population, and they also resemble the results obtained for Polish [33] and German population [34].…”

“…In contrast to rs699, AGT rs4762 polymorphic variant (T207M, T174M) was not included in the meta-analyses, as most individual studies did not show the association of rs4762 with DN [25,27] nor with ESRD [31]. The association of rs4762 with DN was only confirmed in Taiwanese population [27].…”

Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Susceptibility to Osteoarthritis of the Knee: A Case-Control Study and Meta-Analysis

“…Because the role of ACE in knee OA may involve many possible pathways that even include opposing effects, we considered that the source of heterogeneity might include molecular factors such as gene–gene interactions. In fact, complex gene–gene interactions in the RAS were reported in the context of other diseases [ 73 ], which involved gene polymorphisms of ACE I/D. Future studies should further investigate the epistasis analysis of ACE I/D and knee OA [ 74 ].…”

Prognostic Role of A1166c Polymorphisms of the Angiotensine Ii Receptor Gene (Agt2r1) in Coronary Atherosclerosis Among Adyghea Republic Inhabitants

“…Вместе с тем, результаты многоцентровых исследований по ассо-циации SNP А1166С гена AGT2R1 с риском развития БСК для разных этнических групп противоречивы и неоднозначны. Единичные работы в России не отражают генетического разнообразия в распреде-лении 1166С полиморфизмов гена AGT2R1 и их ассо-циаций с ССЗ [8][9][10][11][12][13][14][15].…”