Association Analysis Between TLR4,LBP Genetic Polymorphsims And Cerebral Infarction

Background and ObjectiveIt has been widely accepted that atherosclerosis is an inflammatory disease with immune responses during both the initiation and the progression of this disease .Toll receptor (TLRs), a transmembrane signal transduction family on the surface of the human and mouse cells, mediated natural immune-mediated signal transduction. In recent years, TLRs have been reported to play an important role in the development and progression of atherosclerotic(AS) lesion. However, few studies have ever addressed the relationships between TLR4 and cerebral infarction (CI) . Therefore, association of gene polymorphisms in two genes play key roles in TLR4 signaling pathway with CI risk was studied in our study. Four single nucleotide polymorphisms, i.e Asp299Gly and Thr399Ile at TLR4 locus and Cys98Gly and Leu436Pro at LBP locus were selected. The aim of this study was to further explore the mechanism of cerebral infarction through an association study, and thus provide theoretical evidence for the prevention and treatment of CI.MethodsBy using method of PCR-RFLP, genotypes and allele frequencies for polymorphisms TLR4 Asp299Gly, TLR4 Thr399Ile, LBP Cys98Gly, and LBP Leu436Pro were determined in 366 CI patients and 200 controls from Changsha area in Hunan Province. Blood fat and lipoprotein levels were detected. Statistical analysis was carried out by SPSS14.0 software.Results1. Genotype frequencies for TT, TC, and CC genotypes for LBP Cys98Gly were 85.5%, 14.5%, and 0%, respectively, and the allele frequencies for T,C alleles at this polymorphic site were 92.8% and 7.2%, respectively. For the LBP Leu436Pro polymorphism, genotype frequencies for TT, TC, and CC were 85.5%, 14.5%, and 0%, respectively, and allele frequencies for T and C alleles were 92.8% and 7.2%, respectively.2. No significant difference in genotype and allele distribution of the LBP Cys98Gly and LBP Leu436Pro polymorphism was observed between the cases and controls.3. Subjects carrying TC genotypes for both the LBP Cys98Gly and the LBP Leu436Pro polymorphisms showed higher carotid IMT than TT genotype.4. No significant difference in fasting blood glucose and lipid levels was observed between LBP genotypes.5. The TLR4 Asp299Gly and Thr399Ile genetic polymorphisms were not observed in all 366 cases from Hunan Changsha.Conclusions1. LBP Cys98Gly and Leu436Pro polymorphisms are associated with carotid IMT in Changsha, China.2. LBP Cys98Gly and Leu436Pro polymorphism may not associate with the risk of atherosclerosis cerebral infarction in Changsha, China.3. LBP Cys98Gly and Leu436Pro polymorphisms are not associated with levels of either fasting blood glucose or lipid metabolism in Changsha, China.4. TLR4 Asp299Gly and Thr399Ile gene polymorphisms were not detected in 366 CI cases in Changsha population.