Association of genetic polymorphisms at beta-adrenergic receptor with risk of intracerebral hemorrhagic stroke in North Indian population: a case control study.

Abstract

Stroke is a multifactorial, polygenic disorder, influenced by both environmental and genetic factors. The purpose of this study was to determine the association of beta-1 and beta-2 adrenergic receptor (AR) polymorphisms with intracerebral hemorrhagic stroke (ICH) in a North Indian population. One hundred and six patients with intracerebral hemorrhage (ICH) and 106 age- and sex- matched controls were recruited. Genotyping was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RFLP results of three samples of each genotype were confirmed by DNA sequencing. Mean age of cases and controls were 53.47 ± 14 and 52.92 ± 13.4, respectively. Significant association between Ser49Gly polymorphism of beta-1 AR and ICH in patients who had onset of disease at a later stage of life (>50 years) under a dominant model of inheritance (OR, 3.6; 95% 1.4 to 9.7) was observed. Under the dominant model of inheritance, Gln27Glu polymorphism of beta-2 AR was associated with risk of ICH (OR, 3.2; 95% CI, 1.7 to 5.8) and significant association persisted even after adjustment for demographic and other risk factor variables (OR, 2.9; 95% CI, 1.04 to 8; P = 0.04). Age-stratified analysis showed an independent significant association of Gln27Glu polymorphism of beta-2 AR with risk of ICH in patients those had onset of disease at young age (<50 years) under a dominant model of inheritance (OR, 3.5; 95% CI, 1.1 to 11). The present study provides the first preliminary evidence that Gln27Glu polymorphism of beta-2 AR may contribute modest effect in increase in risk of ICH in North Indian Population. Large prospective studies with large sample size are required to confirm these findings.