Association of alpha 2A adrenergic receptor gene (ADRA2A) polymorphism with irritable bowel syndrome, microscopic and ulcerative colitis

Background: Alpha 2 adrenergic receptors (alpha 2 ARs) play a central role in the regulation of systemic sympathetic activity. Prejunctional alpha 2A adrenoceptor regulates through negative feedback at presynaptic nerve ending. A-1291 C>G polymorphism located in alpha 2-adrenergic receptor gene (ADRA2A) has been identified. We investigated the possible association between 1291 C>G polymorphism in the promoter region of ADRA2A in clinical subtypes of IBS, ulcerative and microscopic colitis patients. Methods: This prospective case control study included 92 patients with diarrhea predominant IBS (D-IBS), 44 with constipation predominant IBS (C-IBS), 15 with alternating diarrhea and constipation IBS (M-IBS). 75 ulcerative colitis (UC), 41 microscopic colitis (MC) and 100 healthy controls. The subjects were genotyped by using PCR amplification of the promoter region of ADRA2A gene followed by digestion with the restriction enzyme Mspl. The study was approved by the institute ethical committee. Results: A strong genotypic association was observed between alpha 2A-1291 C>G polymorphism and D-IBS (chi(2)=6.38. df=2, p<0.05). There was no significant difference in alpha 2A-1291 C>G genotype and allele frequency between C-IBS, M-IBS, UC, MIC cases and control subjects. Conclusions: A significant association was observed between alpha 2A-1291C>G polymorphism and D-IBS. Thus, alpha 2 AR gene may be a potential candidate involved in the pathophysiology of D-IBS. (C) 2009 Elsevier B.V. All rights reserved.