Insight into Gene Polymorphisms Involved in Toll-Like Receptor/Interferon Signalling Pathways for Systemic Lupus Erythematosus in South East Asia

Abstract

Polymorphisms in genes involved in toll-like receptor/interferon signalling pathways have been reported previously to be associated with SLE in many populations. This study aimed to investigate the role of seven single nucleotide polymorphisms withinTNFAIP3,STAT4,andIRF5, which are involved in upstream and downstream pathways of type I interferon production, in SLE in the South East Asian populations. Genotyping of 360 Malaysian SLE patients and 430 normal healthy individuals revealed that minor alleles ofSTAT4rs7574865 and rs10168266 were associated with elevated risk of SLE in the Chinese and Malay patients, respectively (P=0.028, odds ratio(OR)=1.42;P=0.035,OR=1.80, respectively). Polymorphisms inTNFAIP3andIRF5did not show significant associations with SLE in any of the ethnicities. Combined analysis of the Malays, Chinese, and Indians for each SNP indicated thatSTAT4rs10168266 was significantly associated with the Malaysian SLE as a whole (P=0.014;OR=1.435). The meta-analysis ofSTAT4rs10168266, which combined the data of other studies and this study, further confirmed its importance as the risk factor for SLE by having pooled OR of 1.559 andPvalue of <0.001.