Genetic Association of MiR-146a with Multiple Sclerosis Susceptibility in the Chinese Population

作者:Li, You; Du, Chen; Wang, Wei; Ma, Guoda; Cui, Lili; Zhou, Haihong; Tao, Hua; Yao, Lifen; Zhao, Bin; Li, Keshen*
来源:Cellular Physiology and Biochemistry, 2015, 35(1): 281-291.
DOI:10.1159/000369695

摘要

Background: miR-146a polymorphisms have been involved in susceptibility to multiple diseases. The aim of the present study was to analyze the potential association between two functional miR-146a polymorphisms (rs2910164 and rs57095329) and multiple sclerosis (MS) in the Han Chinese population. Methods: A cohort of 525 patients and 568 healthy controls were genotyped to detect the two polymorphisms by SNaPshot. Results: No significant differences were detected in the distribution of the two miR-146a polymorphisms between the patients and controls (P > 0.05). However, stratification by gender showed a statistically significant difference in the frequency of the genotype rs2910164 between MS patients and control females (P=0.009). Further stratification analysis by subgroup revealed that the miR-146a rs2910164 C allele conferred a higher risk of developing relapsing-remitting MS (RRMS) (P=0.018). In addition, the rs2910164 C allele was significantly associated with increased expression of miR-146a in patients with RRMS (P=0.025). Moreover, patients with the rs2910164 C allele released more TNF-alpha and IFN-gamma, but not IL-1 beta, compared with individuals carrying the homozygous GG genotype (P < 0.05). Conclusions: Our results provide evidence that rs2910164 may play a role in MS susceptibility in females. The rs2910164 G>C variation may affect the expression of miR-146a and the release of proinflammatory cytokines.