engleski

Analysis of the Ala394Thr polymorphism in NPAS2 coding region of ischemic heart disease patients

At the molecular level, the mammalian circadian clock is controlled by transcriptional/translational feedback loops comprising a set of key elements, so-called ‘clock genes’ involved in regulation of a wide range of circadian rhythms in physiological processes and behavior. Neuronal PAS domain protein 2 (NPAS2), the largest circadian gene, encodes for a member of the basic helix-loop- helix-PAS class of transcription factors and is a crucial component of the mammalian circadian clock. It is expressed primarily in the forebrain as well as in some peripheral organs, and it was found to be highly expressed in cells of the vascular smooth muscle. Several different polymorphisms of NPAS2 gene indeed, have been correlated with susceptibility to numerous ailments including cancer, metabolic syndrome and bipolar disorder. In this study, we investigated the correlation between nonsynonymous polymorphism (Ala394Thr ; rs2305160) in the NPAS2 gene and the risk of developing ischemic heart disease (IHD), the most common heart condition and still the leading cause of death in modern society. We conducted a case control study in 155 IHD patients and 405 controls. Genotyping of Ala394Thr gene polymorphism was performed with TaqMan Pre-designed SNP Genotyping Assay. Our results demonstrate a statistically significant protective correlation (OR= 0.6102, 95% CI: 0, 4162-0, 8945, p=0.01) between heterozygosity, A/G genotype and risk of developing IHD. These findings suggest that A/G genotype may be a protective factor in IHD and should be considered in evaluation of IHD individual risk.

clock genes, NPAS2, polymorphism, ischemic heart disease

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