Single nucleotide polymorphisms in promoter of angiotensin II type 1 receptor gene associated with essential hypertension and coronary heart disease in Chinese population.
OBJECTIVE
To discover single nucleotide polymorphisms (SNPs) in the promoter region of angiotensin II type 1 receptor (AT1) gene and evaluate their associations with the occurrence of essential hypertension (EH) and coronary heart disease (CHD) in Chinese Han population.


METHODS
SNPs detection was performed by PCR-sequencing. The genotype was determined by the same method in a total number of 473 unrelated patients including 160 EH cases, 128 CHD cases, and 185 EH combined with CHD cases as well as 160 healthy controls.


RESULTS
Six SNPs were discovered in the promoter region of AT1 gene. -810A/T was almost in completely linkage disequilibrium with -713G/T, -214A/C, -213G/C, and -153A/G polymorphisms. No statistically association was found in our population between -810A/T polymorphism and EH, the association of -810A allele and CHD was of borderline significant (chi2=3.649, P=0.056). However, significant differences of genotype distributions were observed in the EH combined with CHD group (TT=126, TA=51, AA=8) compared with the EH patients (TT=127,TA=26, AA=7, chi2=6.410, P=0.041) and the healthy controls (TT=130, TA=24, AA=6, chi2=7.742, P=0.021). The EH combined with CHD patients had a significantly increased A allele frequency than the normal references (0.181 vs 0.106, chi2=7.690, P=0.006) and the EH subjects (0.181 vs 0.125, chi2=4.119, P=0.042). Hypertensive patients carrying TA genotype (OR=1.977, 95 % CI 1.160-3.354, P=0.011) or A allele (OR=1.548, 95 % CI 1.015-2.361, P=0.043) had an increased risk for CHD morbidity.


CONCLUSIONS
we firstly report that -810A/T polymorphism in the promoter region of AT1 gene might be a genetic risk factor for the pathogenesis of CHD complicated with EH in Chinese Han population.
Jin
Wei
W
Department of Cardiology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
Liu
Yan
Y
Sheng
Hai-Hui
HH
Jin
Lin
L
Shen
Ya-Yun
YY
Hua
Qi
Q
Lu
Lin
L
Yu
Jin-De
JD
Huang
Wei
W
D000368:Aged; D003327:Coronary Disease / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*
D044140:Receptor, Angiotensin, Type 1