OBJECTIVES: The aim of the study was to investigate the association between angiotensin II type 1 receptor (AGTR1) gene polymorphisms and diastolic heart failure (DHF) in a case controlled study. METHODS: Of 1752 consecutive patients analyzed, 176 diagnosed with DHF and confirmed by echocardiography were recruited. Controls were matched one-to-one by age, sex, hypertension, diabetes, renal function, and medication use. We genotyped 11 single nucleotide polymorphisms (SNPs) according to the HapMap Han Chinese Beijing databank across the AGTR1 gene to capture 96% of the haplotype variance in all SNPs with minor allele frequencies at least 5%. We also genotyped A1166C (rs5186) SNP with known associations with cardiovascular disease and analyzed associations of SNPs and haplotypes with DHF and linkage disequilibrium structure of the AGTR1 gene. RESULTS: In a single locus analysis, SNP rs16860760, rs389566, and rs5186 were associated with DHF (allele specific P = 0.004, 0.002, 0.002, respectively; permuted P = 0.045, 0.022, 0.027, respectively). SNP rs389566, with a minor allele frequency of 20.17%, had an odds ratio (OR) 2.03 for the autosomal dominant model [AA + AT: TT, 95% confidence interval (CI) 1.29-3.19; P = 0.0012] and 1.73 for the additive model (95% CI 1.21-2.48; P = 0.0018) corresponding to a population attributable risk fraction of 27.21%. The haplotypes in a linkage disequilibrium block of rs389566 (T-A-G and A-A-G) were also significantly associated with DHF (permuted P = 0.0125 and 0.0105, respectively). CONCLUSION: We identified risk-conferring genetic variants of the AGTR1 gene for DHF in a Chinese population.
OBJECTIVES: The aim of the study was to investigate the association between angiotensin II type 1 receptor (AGTR1) gene polymorphisms and diastolic heart failure (DHF) in a case controlled study. METHODS: Of 1752 consecutive patients analyzed, 176 diagnosed with DHF and confirmed by echocardiography were recruited. Controls were matched one-to-one by age, sex, hypertension, diabetes, renal function, and medication use. We genotyped 11 single nucleotide polymorphisms (SNPs) according to the HapMap Han Chinese Beijing databank across the AGTR1 gene to capture 96% of the haplotype variance in all SNPs with minor allele frequencies at least 5%. We also genotyped A1166C (rs5186) SNP with known associations with cardiovascular disease and analyzed associations of SNPs and haplotypes with DHF and linkage disequilibrium structure of the AGTR1 gene. RESULTS: In a single locus analysis, SNP rs16860760, rs389566, and rs5186 were associated with DHF (allele specific P = 0.004, 0.002, 0.002, respectively; permuted P = 0.045, 0.022, 0.027, respectively). SNP rs389566, with a minor allele frequency of 20.17%, had an odds ratio (OR) 2.03 for the autosomal dominant model [AA + AT: TT, 95% confidence interval (CI) 1.29-3.19; P = 0.0012] and 1.73 for the additive model (95% CI 1.21-2.48; P = 0.0018) corresponding to a population attributable risk fraction of 27.21%. The haplotypes in a linkage disequilibrium block of rs389566 (T-A-G and A-A-G) were also significantly associated with DHF (permuted P = 0.0125 and 0.0105, respectively). CONCLUSION: We identified risk-conferring genetic variants of the AGTR1 gene for DHF in a Chinese population.
Authors: Tanika N Kelly; James E Hixson; Dabeeru C Rao; Hao Mei; Treva K Rice; Cashell E Jaquish; Lawrence C Shimmin; Karen Schwander; Chung-Shuian Chen; Depei Liu; Jichun Chen; Concetta Bormans; Pramila Shukla; Naveed Farhana; Colin Stuart; Paul K Whelton; Jiang He; Dongfeng Gu Journal: Circ Cardiovasc Genet Date: 2010-09-22
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