The Study Of Relationship Between Two Frequent Polymorphisms In The Protein S Gene (PROS1) And Ischemic Stroke

Background and Objective Stroke is a major cause of death in the world and is characterized by high rates of case fatality and disability. Strong evidences from epidemiological and animal studies had implicated genetic influences in the pathogenesis of ischemic stroke. Genetic study plays an important role for uncovering the cause of ischemic stroke. In all risk factors, hematological disorders are mostly caused by gene defect. It was reported that more than teens of polymorphsims in hemostasis system were related to ischemic stroke .Protein S (PS), a kind of vitamin K dependent plasma glycoprotein, is a key factor in anticoagulation that acts as a cofactor for activated protein C in the coagulation cascade to inactivate FVa and FVIIIa. Protein S circulates in human plasma by two forms, free and bound to C4b-B p . Only the free protein S has cofactor activity. Protein S deficiency caused serious thrombosis in vein and artery. Many studies had documented the relationship between the PS deficiency and cerebral infarction. An A to G transition at A2148G (Pro 626)and an A to C substitution at A2698C are two frequent polymorphisms located close to or within the 3'-untranslated region of the PROS1 gene.The two polymorphisms take part in the genetic modulation of plasma protein S levels. There were no studies to show whether the two polymorphisms have protect against or increase the susceptibility the thrombotic risk. Therefore, the purposes of the present study were to investigate the characters of the two polymorphisms in Chinese and the relationship between the two polymorphisms and ischemic stroke.Methods Objects examined were composed of 100 healthy controls, 130 patients with cerebral infarction including 102 sporadic forms and 28 with family history, 10 cerebral infarction pedigrees. Serum levels of tPS and fPS were tested by ELISA methods. PCR-RFLP analysiswas used to detect the two polymorphisms.Results1 The distribution of genotype with A2148G polymorphisms is different between Chinses and Whites. The frequencies of A allele and AA genotype were significantly lower in Chinese than in Whites. G allele and GG genotype were significantly higher than in Whites. There were no significant differences in nt2698C/A polymorphsims between the two rates. Combinating the two polymorphisms, the frequencies of AA;CA and AG;CC were significantly lower in Chinese than in Whites, and GG;CC significantly were higher than Whites.2 The frequencies of all genotypes in A2148G haven't fignigicant difference between controls and cerebral infarct patients. The frequency of CC genotype in C 2698A were significantly higher in CI patients than in controls.The frequencies of GG genotype in A2148G and C allele and CC genotype in C2698A were significantly higher in pedigree patients than in controls. Combinatingthe two polymorphisms, GG;CC were singnificantly higher in pedigree patients than in controls. There were no significant difference in two polymorphisms between the patients with and without family history.The frequency of AA genotype in C2698 A were significant lower in members of pedigrees than in controls.3 The plasma levels of tPS and fPS in controls were influenced by sex and age. They were higher in men than in women, and higher in old than in young. The differences were all significant.4 The plasma levels of tPS and fPS in patients with acute phase are significant lower than in controls. And fPS level was lower in pedigree patients than in patients without family history. The levels of tPS and fPS in patients without family history were higher in men than in women. In same sex, the older was higher than younger. The differences are significant. However, there are no different in patients with family history.5 In convalescent phase, the plasma levels of tPS and fPS were also significantly lower than controls, but higher than patients in acute phase. There were no differences between patients with and without family history.6 The plasma levels of tPS and fPS in the healthy pedigree member...