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

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 (rs476...

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Main Authors: Sui-Lung Su, Hsin-Yi Yang, Chia-Chao Wu, Herng-Sheng Lee, Yuh-Feng Lin, Chi-An Hsu, Ching-Huang Lai, Chin Lin, Sen-Yeong Kao, Kuo-Cheng Lu
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:The Scientific World Journal
Online Access:http://dx.doi.org/10.1155/2014/169798
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author Sui-Lung Su
Hsin-Yi Yang
Chia-Chao Wu
Herng-Sheng Lee
Yuh-Feng Lin
Chi-An Hsu
Ching-Huang Lai
Chin Lin
Sen-Yeong Kao
Kuo-Cheng Lu
author_facet Sui-Lung Su
Hsin-Yi Yang
Chia-Chao Wu
Herng-Sheng Lee
Yuh-Feng Lin
Chi-An Hsu
Ching-Huang Lai
Chin Lin
Sen-Yeong Kao
Kuo-Cheng Lu
author_sort Sui-Lung Su
collection DOAJ
description 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.
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spelling doaj-art-555433bd925b448193d384458fc472cd2025-08-20T02:05:06ZengWileyThe Scientific World Journal2356-61401537-744X2014-01-01201410.1155/2014/169798169798Gene-Gene Interactions in Renin-Angiotensin-Aldosterone System Contributes to End-Stage Renal Disease Susceptibility in a Han Chinese PopulationSui-Lung Su0Hsin-Yi Yang1Chia-Chao Wu2Herng-Sheng Lee3Yuh-Feng Lin4Chi-An Hsu5Ching-Huang Lai6Chin Lin7Sen-Yeong Kao8Kuo-Cheng Lu9School of Public Health, National Defense Medical Center, Taipei, TaiwanSchool of Public Health, National Defense Medical Center, Taipei, TaiwanDivision of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanDepartment of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanDivision of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanSchool of Public Health, National Defense Medical Center, Taipei, TaiwanSchool of Public Health, National Defense Medical Center, Taipei, TaiwanGraduate Institute of Life Sciences, National Defense Medical Center, Taipei, TaiwanSchool of Public Health, National Defense Medical Center, Taipei, TaiwanDivision of Nephrology, Department of Medicine, Cardinal Tien Hospital, School of Medicine, Fu Jen Catholic University, New Taipei City, TaiwanObjective. 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.http://dx.doi.org/10.1155/2014/169798
spellingShingle Sui-Lung Su
Hsin-Yi Yang
Chia-Chao Wu
Herng-Sheng Lee
Yuh-Feng Lin
Chi-An Hsu
Ching-Huang Lai
Chin Lin
Sen-Yeong Kao
Kuo-Cheng Lu
Gene-Gene Interactions in Renin-Angiotensin-Aldosterone System Contributes to End-Stage Renal Disease Susceptibility in a Han Chinese Population
The Scientific World Journal
title Gene-Gene Interactions in Renin-Angiotensin-Aldosterone System Contributes to End-Stage Renal Disease Susceptibility in a Han Chinese Population
title_full Gene-Gene Interactions in Renin-Angiotensin-Aldosterone System Contributes to End-Stage Renal Disease Susceptibility in a Han Chinese Population
title_fullStr Gene-Gene Interactions in Renin-Angiotensin-Aldosterone System Contributes to End-Stage Renal Disease Susceptibility in a Han Chinese Population
title_full_unstemmed Gene-Gene Interactions in Renin-Angiotensin-Aldosterone System Contributes to End-Stage Renal Disease Susceptibility in a Han Chinese Population
title_short Gene-Gene Interactions in Renin-Angiotensin-Aldosterone System Contributes to End-Stage Renal Disease Susceptibility in a Han Chinese Population
title_sort gene gene interactions in renin angiotensin aldosterone system contributes to end stage renal disease susceptibility in a han chinese population
url http://dx.doi.org/10.1155/2014/169798
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