| Background Coronary artery disease(CAD) is a common disease endangering the human health seriously. In the fatal cardiovascular disease, coronary heart disease accounted for75%. If males younger than 55 years old, female patients younger than 65 years old, it is called premature coronary artery disease(p CAD). PCAD is a special case of coronary heart disease. With respect to late-onset coronary artery disease, the early onset of coronary heart disease patient gets more reduced quality of life and the economic burden. Genetic factors are one of the major risk factors for premature coronary heart disease, which determine the incidence of p CAD with the synergistic effect of environmental factors. H19 gene is located on human chromosome 11P15.5,and contains 5 exons and 4 introns.The H19 gene codes for a 2.3 kb mature m RNA product.Because of the lack of obvious open reading frame,it is known as long noncoding RNA.The expression of H19 is strongly induced during embryogenesis and downregulated after birth, except in adult skeletal muscle and heart. The H19 gene is expressed exclusively on one parental allele in a phenomenon known as imprinting. H19 is only transcribed from the maternally inherited allele; the paternal H19 allele is not expressed. H19 is involved in the normal embryonic growth,development and children’s growth, behavior development children. Moreover,genetic studies also found that polymorphisms in H19 are correlated with CAD risk factors, including obesity, birth weight, and blood pressure.In this study we aimed to explore the relationship between polymorphisms in H19 gene and the risk of p CAD and provide a new genetic marker for coronary heart disease.Method:The p CAD patients were consecutively recruited from the inpatients who were admitted to the First Affiliated Hospital of Nanjing Medical University with males younger than 55 years old, female patients younger than 65 years old. PCAD was defined as angiographic evidence of at least one segment of a major coronary artery with >50% organic stenosis with males under 55 years old and female patients under65 years old. The 776 cases of control subjects were selected during the same period in the same hospital from the health examination center,sex matched. Considering it was unethical to perform coronary angiography to rule out the presence of asymptomatic CAD, the following inclusion criteria were used: no history of angina,no symptom or sign of other atherosclerotic vascular disease. Measure blood pressure, height, weight, fasting blood glucose and blood lipid level. Genomic DNA was isolated from peripheral blood by using Wizard® Genomic DNA Purification Kit (Promega Corporation, Madison, WI, USA). Genotyping was performed with the Taq Man SNP Genotyping Assay using the ABI 7900 HT real-time PCR system(Applied Biosystems, Foster City, CA, USA) for four polymorphisms including:rs2067051, rs2251375, rs217727, rs4929984.Results:Our data showed that the T variant of rs217727 was associated with a increased risk of CAD(p<0.001). The risk of patients with T allele and TT homozygous genotype was 2.66 times(OR=2.66, CI=1.62~4.36) and 3.00 times(OR=3.00, CI=1.74~5.17)than that CC homozygous genotype. Stratified analyses showed that the risk of premature coronary heart disease risk of non-smokers with risk genotype was significantly higher. No significant result was found in smokers. Moreover, CAD patients with more risk alleles also had significantly higher Gensini scores than those with less risk alleles(P = 0.008)Conclusion:Our study demonstrates for the first time that the rs217727 polymorphisms of H19 are associated with the risk and severity of p CAD in a Chinese population. While H19 gene rs217727 polymorphism is also associated with the susceptibility of premature CAD, T allele may be a genetic susceptibility factor of premature CAD. Future studies are needed to explore the underlying mechanisms of our findings. |
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