Research On The Relationship Between The TGFB1 SNPs And Haplotypes And Stroke In Han People In Changsha Area

Backgroud and objective:20 years of clinical epidemiological study showed that Changsha was the area of high stroke morbidity in the world. Supported by Eighth and Ninth Five-Year Plan, our previous studies showed that although there was no significant difference of the levels of blood lipid, blood glucose and BMI and other traditional risk factors, the stroke morbiditiy of Han population in Changsha area was higher than other areas. This suggests that there are some other factors in additional to the traditional risk factors. So far, it is known that stroke is multigenic disease, genetic factor play an important part in stroke. But the specific genetic machanisms of stroke are still unknown. Our previous studies showed that apoH, apoA and other gene polymorphism related with lipid metabolism were associated with the stroke of Han population in Changsha. In this study, we try to find a gene that have multiple action to stroke.Atherosclerosis is pathologic processes happen in both cerebral infarction and hemorrhage, which affected by many factors. Except for such as hypertension, hypelipidemia, smoking, drinking and other traditional factors, inflammatory cells and cytokine secreted by inflammatory cells are associated with the atherosclerosis. It has been proved that TNF, IL-6, IL-10 and other cytokines were related to this process.As a multifunctional cytokine, TGF-β1 is associated with atherosclerosis, hypertension and metabolism of lipid. Many studies showed TGFB1-800G>A,-509CT and+869T>C can regulate the expression of TGFB1 and the serum level of TGF-β1. The three SNPs are in linkage disequilibrium, they maybe affect the expression of TGFB1 togetherly. Some studies showed that the TGFB1 SNPs were related to the atherosclerosis and hypertension. Based on the fact, we hypothesis that these SNPs have association with stoke of Han population in Changsha area. Untill now, there is no related reports about the relationship between these SNPs and stroke in Changsha area.Through research of the TGFB1 SNP of Han population in Changsha area in this study, we will explore the relationship between the TGFB1 SNPs and the stroke in this area, reveal the genetic reason that the high morbidity of stroke in Changsha and find some dependable genetic marks of stroke. At the same time, it will provide molecular epidemiology evidence to screen the high-risk group of stroke and theoretical basis for gene function research, treatment and prevention of stroke.Method:The genotypes of 186 patients with cerebral infarction,202 patients with primary cerebral hemorrhage and 160 sex- and age-matched heath controls from Han population in Changsha area were detected by PCR-RFLP and direct DNA sequencing.χ2 test was used to check the Hardy-Weinberg balance of the genotype and compare the other numeration date. t test and AVONA analysis of variance was used to analysze the measurement date. Logistic regression analysis was used to evaluate the risk of onset of stroke of the subjects with different genotypes. The haplotypes and the linkage disequilibrium between TGFB1-800G>A,-509C＞T and +869T>C were analyzed by SHEsis (http://analysis.bio-x.cn/myAnalysis.php). D' and r2 are used to evaluate the linkage disequilibriuim.Result:1. The distribution of-800G>A gentypes and alleles is not different between CI growp and the control (P>0.05), no difference is observed between the CH group and the control group (P>0.05). There is no difference of the distribution of-800G>A genotype and allele between the H subgroup and the WH subgroup in CI group, and also in CH and control group. When the three groups were divided into AP and WAP subgroups respectively, no differences were found between the two subgroups in each group. GG carriers had lower serum levels of TC than the A allele carriers (P<0.01), while GG carriers had lower serum level of LDL-C than A allele carries in control group(P<0.01).2. The frequencies of the-509C＞T and +869T>C genotypes and alleles are not different between the CI and the control groups, no difference was found between the CH and the control groups(P＞0.05). But the frequencies of-509T and +869C carriers in FCI is higher than control group, the stroke prevalences of the-509T carriers in FCI is 1.557 multiples compared to the control group, while the +869C carriers in FCI is 1.45 multiples compared to the control group. There is no difference of the distribution of -509C>T and +869T>C genotypes and alleles between the H subgroup and the WH subgroup in CI group, no difference was found in CH and control group(P＞0.05). The frequencies of the-509C>T and +869T>C genotypes and alleles are not different among the subgroups with different atherosclerotic plaque(P>0.05). Serum levels of TG, TC, HDL-C and LDL-C of different-509C＞T and +869T>C genotypes carriers are not different(P>0.05).3.-509C>T and +869T>C are in high linkage disequilibrium, but they are in low linkage disequilibrium with-800G>A (D'=0.098, r2=0.000; D'=0.019; r2=0.000). Two major haplotypes of TGFB1 were found in the Han people in Changsha area, they are-509C/+869T and-509T/+869C. The frequencies of the two haplotypes are not different between the CI and control growps, and are not different between the CH and control groups.Conclusion:1. TGFB1-509C>T and +869T>C are associated with cerebral infarction of the people with a family history of cerebral infarction, but are not related to cerebral hemorrhage.-509T and +869C alleles are probably the risk factors of stroke of the people with history of cerebral infarction.2. TGFB1-800G>A is related to the serum level of TC. A allele are probably the risk factor of high TC levels.3.-509C＞T and+869T>C are in high linkage disequilibrium, but the haplotypes are not associated with both cerebral infarction and hemorrhage.