Polymorphisms In The HMG-CoA Reductase Gene And Their Association With Coronary Heart Disease

Though the vast majority of the human genome had been sequenced, Much work , including the analysis of the polymorphisms of the human genome, remains to understand how this "instruction book for human biology" carries out its multitudes of functions. But the consequences for the practice of medicine are profound. Genetic prediction of individual risks of disease and responsiveness to drugs will reach the medical mainstream in the next decade or so. The development of designer drugs will be based on a genomic approach to targeting molecular pathways that are disrupted in disease.Number factors are risk for coronary heart disease (CHD), they can be grouped into factors with an important genetic component, and those that are environmental. The genetic factors determine and affect the other risk factors such as the level of plasma lipoprotein , diabetes, obesity and so on. The relative abundance of the different plasma lipoproteins appears to be of primary important for most forms of CHD. Because of their central role in regulation lipid metabolism and multiple genes involved, the human HMG-CoA reductase gene is likely to have an important influence on the development of CHD , as it is the limited enzyme that catalyze the cholesterol synthesis.The aim of present work was to study the polymorphisms of HMG-CoA reductase gene in Chinese Han population and test whether they associated with CHD.Study revealed that there are no HgiA1 polymorphisms in Chinese Han population, allelic frequencies of ScrFl restriction polymorphism of the HMG-CoA reductase(HMGR) gene were 0.519, 0.481 , There was no significant difference in frequencies of alleles and genotypes in ScrFl polymorphism between CHD group and control group(P > 0.05).However, the levels of plasma VLDL and TG with AA genotype in CHD group were higher than those in CHD patients with other genotypes(P < 0.05). The frequencies of A, a alleles at ScrFl polymorphic site were significantly different from those reported in European Caucasians ( 0.44 vs. 0.55,0.56 vs. 0.45, P<0.05) . As to the TTA polymorphisms Seven alleles, namely 10-16 were found in both groups. Comparison of the alleles frequency of the TTA polymorphism of the HMGCR gene in CHD and control groups revealed thatthe allele 13 was present at a significant higher frequency in the CHD group than in the control group (p<0.05) , while the allele 14 was present at a lower frequency in patient group than in the control group(p=0.002). The frequency of 13-positive cases was also significantly increased in the patient group as compared with controls. Exon 6,7,8,11,15 of HMGCR gene were analysed by using the PCR-SSCP method, but mutations were not found.