Study On The Ralationship Between Genetic Polymorphism Of Platelet Glycoprotein Ibαand Coronary Artery Disease

BackgroundCoronary artery disease (CHD) is one of the serious diseases to humanbeing. In the 1960s, people recognized that hypertension, hyperlipemia, smoking and diabetes mellitus are the dangerous factors for CHD. But in all the etiopathogenisis of CHD, only two-thirds account for these can controlled factors. Recently years, more and more evidences show that the prevalence of CHD should attribute to the interactions of genetic susceptibility, long-lasting environmental influence (hormone, smoking, overweight) and intercurrent disorders (diabetes, hypertension, dyslipidemia, hyperhomocysteinemia). The thrombosis of coronary artery attributing to the rupture of atherosclerotic plaque consists of the physiological basic of CHD. Glycoprotein (GP) Ib-IX-V is a platelet membrane receptor complex. Under high shear stress, it plays a key role in platelet activity and thrombosis. GP Ib-IX-V receptor complex consists of four different polypeptide chains. GPIbαis one of the important chain of the complex and its gene polymorphism may influnce the structure and quantity of the receptor complex, which further influnce the platelet adhere, activity and aggregation. By now, the relationship between the polymorphism of GPIbαand CHD remains controversial and there are less large scale research. So it will be epoch-making significance if we study the etiopathogenisis of CHD from the genetic ascept.ObjectiveTo explore the three genetic polymorphisms of platelet membrane glycoprotein Ibαin population of Henan Han district. The genotypes of Human Platelet Alloantigens-2 (HPA-2) polymorphism, Kozak sequence polymorphism and Variable Number of Tandem Repeats(VNTR) polymorphism were analyzed to investigate the relationships between their genetic polymorphisms and the development, the severity of CHD.MethodsA total number of 403 CHD patients hospitalized in the department of cardiovascular medicine (including 243 myocardial infarction (MI) patients and 161 unstable angina (UAP) patients) and 500 healthy controls recruited by random sampling without familiy history of CHD were investigated by case-control studied. All subjects enrolled in the study were Han People in Henan district. Genomic DNA was purified from venous blood. PCR or PCR-RFLP methods were used to detect the genotypes of HPA-2, kozak sequence and VNTR in all these subjects. For patients underwent coronary angiography, the severity of coronary heart diseases was estimated according to the Gensini score of CHD so as further to establish the relationship between the severity of CHD and these genotypes.Results1. HPA-2 gene1.1 There were three genotypes of HPA-2 in Han People of Henan district: TT, TM and MM.1.2 The distribution of the three genotypes were compatible with the Hardy-weinberg equilibrium in the CHD group and control group.1.3 There were significant differences of TM+MM genotype distributions between CHD group and control group, P<0.05. Between control group and MI subgroup or UAP subgroup, the distributions of TM+MM genotpye didn't reach ststistics significance. P>0.05.1.4 Between control group and CHD group or MI subgroup, the differences of T, M alleles distribution reached statistics significance, P<0.05, while, there were no significant differences of T, M alleles distributions Between control group and MI subgroup or UAP subgroup, P>0.05.1.5 In CHD group, MI subgroup and UAP subgroup, the differences of Gensini score between CC genotype and (TT+TC) genotypes didn't reach ststistics significance, P >0.05.2. kozak sequence gene2.1 There were three genotypes of kozak sequence in Han People of Henan district: TT, CT and CC. 2.2 The distribution of the three genotypes were compatible with the Hardy-weinberg equilibrium in the CHD group and control group.2.3 Between control group and CHD group or MI subgroup, the differences of CC genotype distribution reached statistics significance, P<0.05, while, there were no significant differences of CC genotype distributions Between control group and UAP subgroup, P> 0.05.2.4 It proved no association between any alleles and CHD, MI or UAP, P>0.05.2.5 In CHD group, MI subgroup and UAP subgroup, the differences of Gensini score between CC genotype and (TT+TC) genotypes didn't reach ststistics significance. P >0.05.3. VNTR gene3.1 There were six genotypes of VNTR in Han People of Henan district: AC, BC, BD, CC, CD and DD.3.2 It proved no association between any genotypes or alleles and CHD, MI or UAP.3.3 In patients with CD genotype, the differences between Gensini score≥40 group and Gensini score <40 group reached statistics significance, P<0.05.4. multigenic analysis4.1 HPA-2 gene and VNTR genebetween CHD group and control group, the differences of CD+(TM+MM) genotypes distributions didn't reach statistics significance, P>0.05..4.2 Kozak sequence gene and VNTR genebetween CHD group and control group, the differences of CD+CC genotypes distributions reached statistics significance, P<0.05.4.3 Kozak sequence gene and HPA-2 genebetween CHD group and control group, the differences of CC+(TM+MM) genotypes distributions reached statistics significance, P<0.05.4.4 HPA-2 gene, Kozak sequence gene and VNTR genebetween CHD group and control group, the differences of (TM+MM) +CC+ CD genotypes distributions didn't reached statistics significance, P>0.05.5. The influence of risk factors to MILogistic regression analys shows that age, diabetes, hypertension, smoking and hyperlipemia were independent risk factors for the prevalence of MI. Conclusions1. There are polymorphisms of The HPA-2 gene, the Kozak sequence gene and the VNTR gene in Han People of Henan province. The distribution of these three gene polymorphism may exist racial and district differences.2. There is association between the HPA-2 polymorphism and CHD. The M+ genotypes can be an important risk factor for CHD.3. There is association between the polymorphisms of kozak sequence -5T/C polymorphism and CHD. The CC genotype can be a marker of genetic susceptibility about CHD.4. There is an association between The CD genotype of VNTR in platelet membrane GPIbαgene and the severity of CHD.5. There are increasing risks for CHD in people with genetypes of Kozak sequence CD+ VNTR CC, and in people with genetypes of Kozak sequence CD+ HPA-2 M(+). But other combining genetypes may not be the increasing risk factor for CHD.6. M(+) genotyes of HPA-2, CC genotype of Kozak sequence and CD genotype of VNTR can be work in the development of MI accompanied with the environmental influence and intercurrent disorders.