Impact of gene polymorphisms in renin-angiotensin-aldosterone system, environment risk factor and their interactions with risk of end-stage renal disease

• Main Authors: Hsu, Chi-An, 許濟安
• Other Authors: Su, Sui-Lung
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/43457220583175527108

碩士 === 國防醫學院 === 公共衛生學研究所 === 101 === Background: In Taiwan, the prevalence of end-stage renal disease (ESRD) reached 2,584 per million in 2010, which requires major intervention in the form of dialysis or transplant. The impact of ESRD on public health and health care economics has been a global focus for years. It has been reported that some single nucleotide polymorphisms (SNPs) of the renin-angiotensin-aldosterone system (RAAS) gene are associated with the development of ESRD. Object: The aim of the present study was to explore whether renin-angiotensin-aldosterone system gene SNPs, as well as their interactions are associated with the end-stage renal disease. Materials and Methods: The study group consisted of 647 patients with ESRD from Cardinal Tien Hospital. The control group involved 644 healthy individuals from Tri-service General Hospital. All subjects were genotyped for the polymorphism of the renin-angiotensin-aldosterone system gene by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Multifactor dimensionality reduction was used to explore interaction models and logistic regressions were used to confirm them. Results: Significant associations were observed in polymorphisms of AGT M235T, ACE I/D, G2350A and CYP11B2 C-344T between ESRD patients and healthy individuals. In AGT M235T polymorphism, M allele was a protection against ESRD (OR=0.7, 95%CI: 0.55-0.89). In ACE I/D polymorphism, D allele was a risk factor towards ESRD (OR=1.29, 95%CI: 1.08-1.54). In ACE G2350A, G allele was a risk factor towards ESRD (OR=1.31, 95%CI: 1.1-1.56). In CYP11B2 C-344T, the TC genotype compared with TT genotype was a protection against ESRD (OR=0.7; 95%CI: 0.54-0.91). There was no difference in AGT T174M, AGTR1 A1166C and AGTR1 C573T genotype distribution between ESRD patients and healthy individuals. With MDR analysis, we found that the three-locus model (ACE ID/ACE G2350A/CYP11B2 C-344T) gene-gene interaction was the best model for ESRD risk prediction. After involved some environment risk factors in the MDR analysis, we found that the four-locus model (BMI/ACE I/D/ACE G2350A/CYP11B2 C-344T) interaction was the best model for ESRD risk prediction. Conclusion: We conclude that AGT M235T, ACE I/D, ACE G2350A and CYP11B2 C-344T were the likely candidate determinants of ESRD. There was an three-locus model gene-gene and four-locus model gene-environment interaction was the best model for ESRD risk prediction. Further studies are needed to confirm this finding.