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

Abstract EN

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.