Role of angiotensin II type I (AT1 A1166C) receptor polymorphism in susceptibility of left ventricular dysfunction.

backgroundLeft ventricular dysfunction (LVD) with subsequent congestive heart failure (CHF) constitutes the final common pathway for a host of cardiac disorders. The impaired LV function develops in response to an ischemic insult followed by a fall in cardiac output that leads to activation of renin-angiotensin-system (RAS). Angiotensin II type I receptor (AT1), which mediate the vasoconstrictive and salt-conserving actions of the RAS, represent interesting candidate genes for cardiovascular diseases. Therefore, we conducted an association study between single nucleotide polymorphism (SNP) in AT1 gene and LVD in CAD patients. METHODS AND

resultsThe present study recruited a total of 950 subjects including 720 angiography confirmed CAD patients and 230 healthy controls. Among 720 CAD patients, 229 with reduced left ventricle ejection fraction (LVEF≤45%) were categorized as LVD. The AT1 (A1166C, rs5186) polymorphism was determined by ARMS-PCR. Our results showed that the frequency of AT1 1166AC and CC genotypes were significantly higher in LVD patients in comparison to non-LVD (LVEF >45%) patients (p value = 0.003; OR = 1.81 and p value <0.001; OR = 4.33). Further analysis showed that AT1 A1166C polymorphism was significantly associated with LV end diastole (p-value = 0.031), end systole (p-value = 0.038) dimensions, and mean LVEF (p-value = 0.035). Moreover, on comparing the AT1 A1166C polymorphism in CAD patients with healthy controls, we did not find any association both at genotypic and allelic level (p value = 0.927; OR = 1.04 and p value = 0.219; OR = 0.83) respectively.

conclusionsOur study suggests that AT1 A1166C polymorphism may play significant role in conferring genetic susceptibility of LVD.