Study On The Association Of Platelet Glycoprotein Ia807T/C Gene Polymorphism With The Susceptibitity To Ischemic Cerebrovascular Disease In Han Population Of Henan Province

Background and objectiveCerebrovascular disease(CVD) is a common and frequently-occurring disease which can threaten people,s health ,the high attack rate and mortality of CVD will result in heavy burden to family and society.Many risk factors such as hypertension,hyperglycosemia,hyperlipemia and smoking et al to CVD have been assured. Among the cerebrovascular diseases, ischemic cerebrovascular diseases (ICVD) were about 80%,but its pathogenesis could not been understood clearly.Our country has a high rate of ICVD and the age of onset is becoming younger and younger.Now studies on ICVD risk factors are the important researching directions,especially genetics aspects.In recent years, molecular biology develops rapidly and it can open up a new area for genetic research of ICVD.Currently we should try to find the virulence gene of ICVD and identify the high risk group of ICVD ,so that provide more energetic preventions and cure strategics for ICVD patients.Collagen plays an important role in the process of occurrence and development of aggregation and thrombosis.The polymorphsim of platelet membrane glycoprotein Ia(GPIa) plays an important role in the process of arterial thrombosis,it can be conjuncted by the collagen through the membrance rectptor GPIa/IIa, then producing powerful singal mediating platelet aggregation. Eventually it resulted in platelet aggregation and thrombus formation. In recent years,two types of polymorphism had been found in the GPIa gene transcription district 807(C or T)and 873(G or A),both 807T and 873A were completely chained. It was reported that the polymorphism was significantly related to the level of GPIa-IIa on the surface of platelet. By now, the relationship between the polymorphism of GPIa and ICVD remains controversial and there are less large scale research. So it will be epoch-making significance if we study the etiopathogenisis of ICVD from the genetic ascept.Thus to study the association between the polymorphisms of platelet glycoprotein receptor Ia and ischemic cerebrovascular disease will have great influences on treatment and precaution against ischemic cerebrovascular diseases.This study will analyse GPIaC807T gene polymorphisms in Henan Han populations,to investigate the distribution of GPIa gene C807T in Henan Han populations ,so that to explore the role GPIa polymorphisms play in the development process of ICVD.Aim to further approach the etiopathogenisis and pathogenesis of ICVD,in order that provide new strategy for prevention ICVD accordingly.MethodsAccording to the diagnosis criteria on stroke which was revised by WHO in 2006, a total of 317 patients with ICVD from unrelated kindred of Chinese Han ethnicity in Henan area were inpatients admitted to the top two hospitals of Henan province from September 2008 to June 2009.In the ICVD group, there were 171 males and 146 females aging from 38 to 75 years old, with an average age of 56.5±18.5 years old.They were diagnosed as ICVD by clinical symptoms and CT or MRI scan. Among these ,we can define cerebral infarction group among individuals yonger than the mean age of 55 years and high-risk factors group according to Essen Stroke Risk Scale(ESRS) and Framingham Stroke Processing(FSP). 311 healthy outpatients admitted to the top two hospitals in Henan province as controls, including 311 healthy individuals (165 males and 146 femals) aging from 39 to 76 years old, with an average age of 57.5±18.5 years old. There was no significant difference(p>0.05) in the composition of gende,age,blood pressure,lipid level,blood glucoses and smoking history between the two groups ,the people who had epilepsy,tumor,liver or kidney dysfunction,serious malnutrion were excluded from the two groups .So they can be comparable .Peripheral venous blood samples were collected from every object. Genomic DNA was extracted from white blood cells. Using the primers,we performed PCR- RFLP (polymerase chain reactionnd-refined frequence length polymorphism) amplification. These products were electrophoresed on 2.5% agarose gels,and DNA was visualized by ethidium bromide straining.All the experimental data were input and establish database in SPSS 13.0 software.Genotype and allele frequencies were estimated by the gene-counting method.Hardy-weinberg equilibrium was confirmed with the x2 test. Categorical Parameters were summarized as number(%), and compared with chi-square(x2) -test.The relative risk of genotypes and alleles was described by odds ratios (OR) and 95% confidence intervals (95%CI). And a=0.05 was used as a statistical test standards.Results1.The platelet membrane GPIaC807T has two alleles(C or T) and three genotypes (C/C ,C/T,T/T) in Han population of Henan province.2. The distribution of the three genotypes were compatible with the Hardy-weinberg equilibrium in the ICVD group and control group.3. By contrast to the normal group ,the frequencies of GPIa T allele and TT genotype were significantly higher in cerebral infarction group among individuals yonger than the mean age of 55 years old(x2= 4.01 ,p<0.05) and individuals with high-risk factors (x2=4.98 p<0.05). While, there were no significant differences of T allele and TT genotype distributions between the normal group and the ICVD group, P>0.05.Conclusions1.There exists polymorphisms in platelet membrane GPIaC807T gene in Han population of Henan province. The distribution of these three gene polymorphism may exist racial,age and district differences. 2.The platelet GPIaT807 allele and TT genotype might be independent risk factors for the development of individuals yonger than the mean age of 55 years old and high-risk patients in Han population of Henan province. but there is not association between the polymorphisms of platelet GPIaC807T and the whole ischemic cerebrovascular diseases .