Study On The Association Of FXII,PS And PLG Polymorphisms With Thrombosis

BackgroundThrombosis with high mortality and morbidity are very common in clinical and serious harm to human health. Thrombosis involves blood coagulation, anti-coagulation and fibrinolytic system. High activity of coagulation, low activity of the anticoagulant mechanism and fibrinolyic function may lead to the formation of thrombosis. Thus the protein factors of these paths play an important role in the thrombosis. Activated FXII directly or indirectly activates plasminogen, leading to fibrinolyic. Protein S can inhibit the function of tissue-type plasminogen activator on the glu-type plasminogen activation; Fibrinolysin can split FXIIa and change it to FXII.The coagulation factorXII (FXII: Hageman factor) is an 80-kDa serine protease circulating at an average concentration of 30 ug/ml. In vitro, FXII plays a central role in the initiation of coagulation and fibrinolysis, but its physiological role is still under discussing. The polymorphism (C46T) in the exon1 region of FXII gene exists in the upstream of translation initiation. After T displaces C, the polymorphism destroys FXII gene expression and result in the lower translation efficiency and a decrease in FXII plasma level. In the foreign, there are some researches on the polymorphism (C46T) of FXII gene, but the role of the polymorphism for the development and progression of the thrombosis is still under discussion.Protein S (PS) is physiological anticoagulant, serving as a receptor for the anticoagulant protease, activated protein C, which inactivates blood coagulation cofactor factors Va and VIIIa. PS also inhibits prothrombin complex activity. PS plays an important role in blood coagulation and anticoagulation system in vivo. PS gene exon6A448G is expected to cause a substitution of Lys155 by Glu in the second EGF domain. This inversion may have great influence on the stability and conformation of the second EGF domain of PS molecule. The dysfunction of protein S is suggested to be mainly caused by a lack of interaction with APC required for the expression of the APC cofactor activity and by a lack of interaction with factor Xa required for the inhibition of the prothrombinase complex activity.Plasminogen (PLG) is a key proenzyme of plasmin in the fibrinolytic and thrombolytic systems. PLG is actived in vivo, change to fibrinolysin. Plasminogen/fibrinolysin deficiency is the risk factors of thrombosis. PLG gene exon15G1912A, which makes a substitution of Val601 by Thr, is common in congenital deficiency of plasminogen.To better understand the mechanism of thrombus formation from the perspective of molecular biology, this paper intents to study the distributing frequency of FXII gene exon1C46T, PS gene exon6A448G and PLG gene exon15G1912A polymorphism, and to explore the relation between the polymorphisms with the formation of thrombosis, expecting clinical screening for thrombosis prevention and treatment. Moreover, this is of great significance for further explained the incidence of thrombosis and thrombosis mechanism.Material and Methods:Thrombosis persons: 92 cerebral thrombosis persons from the Nerve Medical Department of Ji-Lin province electric power hospital and 123 from the Nerve Medical Department of JiLin University first hospital. All of them are diagnosed as cerebral thrombosis persons by CT or MRI. 87 vein thrombosis persons from the vascular surgery Department of JiLin University first hospital. All of them are diagnosed as vein thrombosis persons by Color DopplerUltrasonography. PCR-RFLP analysis was used to detect the three polymorphisms.Statistical analysis:Using the SPSS13.0 for window statistical package, count data was performed by the t-test and measure data was performed by chi-squared test. Results1 Polymorphism (C46T) of FXII geneThe distribution of genotype with FXIIC46T polymorphisms is different between Chinese and Whites.The frequencies of C allele and C/C genotype were significantly lower in Chinese than in Whites.T allele and T/T genotype were significantly higher than in Whites. The CI group compared to the normal control group, the frequencies of C allele and C/C genotype are higher, separately is 11.38%,28.05%. There is significant difference by the statistical analysis,P=0.048(X2=3.604). By referring to T/T genotype, the risk odd of C/C genotype is higher 2.68 times than of T/T genotype. OR=2.68, having significant difference (P=0.049).2 Polymorphism (A448G) of PSgeneThe gene PS exon6A448G mutation was not found in all subjects.3 Polymorphism (G1912A) of PLGgeneIn control group, the distributing frequency of the G/G and G/A genotype separately is 71.67%,8.33%. The distributing frequency of G, A allele separately is 95.83% and 4.17%. In CI group , the distributing frequency of the G/G,G/A,A/A genotype separately is 38.23%,47.06% and 17.71%. The distributing frequency of G,A allele separately is 61.76% and 38.24%. There is significant difference by the statistical analysis,PA=PG=0.048, X2 =59.581,suggest relationship between A,G allele and cerebral infarction. 4 Comparison of age and sex among the control group, cerebral infarction group:The significant difference of mean age exits among the control group and cerebral infarction group(P<0.05). On the sex,significant difference is between the control group and cerebral infarction group(P<0.05).Conclusions1 The distribution of genotype in A448G was first reported in Jilin.2 The distribution of genotype in FXII exon1C46T are different between Chinese and Whites. The C/C genotype of FXII exon1 was associated with susceptibility of cerebral infarction.3 PS exon6A448G polymorphism was not found,this mutation is rare in Jilin.4 PLG exon15G1912A polymorphism was associated with susceptibility of cerebral infarction. In the pathogenesis of cerebral, A allele may be a risk factor infarction,and G allele may have significant protection.