The SNPs On CDKN2 Gene Are Associated With Coronary Atherosclerotic Heart Disease

Background:Coronary atherosclerotic heart disease (CAD) is a polygenic inheritance disease. Single nucleotide polymorphises (SNPs) is an important index to enclose the pathogenesis of polygenic inheritance diseas. SNPs is a phenomena that single nucleotide on allele sequence of Genome DNA is distinction on different individuals in the same species. In recent years, more and more studies indicate that oncogene and anti-oncogene may have closely related with atherosclerosis. Some atherosclerotic pathogenetic factor may stimulate oncogene overexpression in the vascular wall. Oncogene activation and anti-oncogene mutation or expression supptessed in atherosclerotic plaque at the same time. CDKN2 gene is a tumor suppressor gene and is also called P16 gene or MTSL. It is located the chromosome 9p21 region, coding the protein of 148 amino acid. It is inhibitory factor of cyclin dependent kinase4. We tested whether six single nucleotide polymorphises(rs10757278,rs10757277,rs10757279,rs10811656,rs1333047 and rs1333049) on chromosome 9p21, associated with coronary atherosclerotic heart disease in Chinese population of the Han nationality.Objective:To test our hypothesis that polymorphisms of rs10757278,rs10757277,rs10757279,rs10811656,rs1333047 and rsl333049 may modify the diversity of CAD.Subjects and methods:Total of 360 consecutive CAD patients established in General Hospital of People's Liberation Army were recruited, and 405 healthy controls were successfully investigated. The DNA was extracted from peripheral blood leukocytes. The statistical software package SPSS 16.0 was used for statistical calculations. Allele and genotype frequencies among cases and controls were compares with values predicted by Hardy-Weinberg equilibrium using the X2-test. For each odds ratio, we calculated 95%confidence intervals (CIs). Logistic regression analysis was performed to identify the independent risk factors for CAD.Results:Our results indicated that the genotype GG of rs10757278 conferred increasing risk for CAD (OR 1.91,95% CI 1.35-2.68). Allele T of rs10811656 conferred increasing risk for CAD (OR 1.67,95% CI 1.26-2.23). The genotype TT of rsl333047 conferred increasing risk for CAD (OR 1.57,95% CI 1.15-2.06)Conclusion:Our data indicate that the variations of three locus-rs10757277,rs10757278,rs10757279,rs10811656,rs1333047 and rs1333049 of the CDKN2 gene is correlated with the increasing risk for CAD independently.