Backgrounds: Vascular atherosclerosis leads to various cardiovascular and cerebrovascular diseases. Nitric oxide (NO) promotes vasodilatation and prevents Coronary Artery Disease (CAD). Pin1 suppresses NO production by down-regulating the activity of endothelial nitric oxide synthase (eNOS). Whether the genetic polymorphisms of the PIN1 gene (encoding Pin1) are implicated in CAD deserves investigations in human beings.
Methods: A total of 210 CAD patients and control individuals (all females) were enrolled, and their genotypes of rs2233679 (-667C/T, a key SNP in the promoter of PIN1 gene) were sequenced. T-test, chi-square test, odds ratio (OR) and 95% confidence interval (95% CI) were calculated to evaluate Hardy-Weinberg equilibrium, varied genetic distribution and relative CAD risk.
Results: The differences in age, BMI, triglyceride, total cholesterol, low-density and high density cholesterol between the CAD and control groups were not significant (all P>0.05), and Hardy-Weinberg equilibrium was observed in the two groups (both P>0.05). The frequency of -667T allele in the CAD group was higher than that in the control group. The genotype -667TT elicited a higher hazardous risk of CAD compared to the genotype -667CC (OR=1.85, 95% CI: 0.75-4.53) as well as the genotypes CC+CT (OR=1.97, 95% CI: 0.86-4.49).
Conclusions: We firstly show that the allele -667T in the PIN1 promoter may elicit a higher CAD-risk than -667C, and the -667TT genotype of PIN1 may be a new genetic biomarker for increased incidence of CAD. These novel observations put forward a new understanding of the PIN1-CAD genetic relationship in humans, potentially contributing to both cardiovascular and cerebrovascular disorders.
Keywords: Cerebrovascular atherosclerosis; Coronary Artery Disease; Genetic susceptibility; PIN1; Single nucleotide polymorphism.
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