TLR 4 rs 1927911 , but Not TLR 2 rs 5743708 , Is Associated With Atherosclerotic Cerebral Infarction in the Southern Han Population ontrol Study

The objective of this study was to explore the association of toll-like receptor (TLR) 4 rs1927911 and TLR2 rs5743708 with atherosclerotic cerebral infarction (ACI) and their effects on blood pressure, fasting blood glucose, and blood lipids in the Han population of Hunan Province. TLR4 rs1927911 and TLR2 rs5743708 were detected by polymerase chain reaction and restriction fragment length polymorphism in 170 patients with ACI and 149 healthy controls. Our results indicated that the genotype and allele frequencies of TLR4 rs1927911 were significantly different between ACI patients and controls, whereas those of TLR2 rs5743708 were not significantly different between the 2 groups. For TLR4 rs1927911, blood pressure, fasting blood sugar, and serum lipid levels were not significantly different among different genotypes in the ACI and control groups. The rs1927911 polymorphism of the TLR4 gene may be a risk factor for ACI in the Southern Han population of Hunan Province; however, it may not be associated with blood pressure, fasting blood sugar, or blood lipids. (Medicine 94(2):e381) Abbreviations: ACI = atherosclerotic cerebral infarction, ANOVA = analysis of variance, BMI = body mass index, CI = confidence interval, DBP = diastolic blood pressure, FBS = fasting blood sugar, HDL = high-density lipoprotein, LDL = low-density lipoprotein, OR = odds ratio, PCR = polymerase chain reaction, , MD, Ning Zhang, MD, and Yunhai Liu, MD INTRODUCTION S troke is one of the leading causes of death in China; with high morbidity, mortality, and disability rates, it is both a serious threat to human health and a substantial burden to society and the patients’ family. Atherosclerotic cerebral infarction (ACI) is the most common type of stroke. The development of ACI is a complex process of interactions between environmental factors and genetic backgrounds. Atherosclerosis is considered as one of the major pathological mechanisms of ACI, and inflammation and immune dysfunction may play a crucial role in the pathogenesis of atherosclerosis. Therefore, genes associated with inflammation and immunity can be considered important candidate genes for ACI. Toll-like receptors (TLRs) are a homologous family of receptors that are responsible for innate immunity. TLR activation can induce the expression of proinflammatory cytokine genes. Overexpression of TLR2 and TLR4 has been shown in atherosclerotic lesions. Studies have found that TLR2 and TLR4 expression levels were associated with the prognosis of ACI. Therefore, TLR2 and TLR4 are considered to play a role in the development and progression of atherosclerosis and ACI. Several studies have shown that Asp299Gly and Thr399Ile variants of the TLR4 gene are associated with stroke risk or poor prognosis. However, other studies have drawn the opposite conclusion. Hang et al noted that the allele frequencies of these 2 single-nucleotide polymorphisms (SNPs) are low, whereas rs1927911 exhibits a high frequency in the Chinese population. Moreover, Yuan et al confirmed that SNPs Asp299Gly and Thr399Ile of the TLR4 gene are rare in the Hunan population. The rs893629 polymorphism of the TLR2 gene was found to be related to the risk of arterial thrombosis in American systemic lupus erythematosus patients. In recent years, the rs5743708 (Arg753Gln) polymorphism of TLR2 has been shown to be relevant to the risk of undergoing percutaneous transluminal coronary angioplasty and restenosis following coronary artery procedures. To date, association studies focused on polymorphisms of the TLR2 gene and ACI risk have not been reported. In this study, polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to detect rs1927911 and rs5743708 polymorphisms in ACI patients and controls from the southern Han population in Hunan province of China. MATERIALS AND METHODS