Research Article Insight into Gene Polymorphisms Involved in Toll-Like Receptor/Interferon Signalling Pathways for Systemic Lupus Erythematosus in South East Asia Hwa Chia Chai, 1,2 Kek Heng Chua, 2 Soo Kun Lim, 3 and Maude Elvira Phipps 1 1 Jefrey Cheah School of Medicine and Health Sciences, Monash University, Sunway Campus, 46150 Selangor, Malaysia 2 Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia 3 Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia Correspondence should be addressed to Maude Elvira Phipps; maude.phipps@monash.edu Received 22 July 2013; Revised 20 December 2013; Accepted 26 December 2013; Published 17 February 2014 Academic Editor: Timothy B. Niewold Copyright © 2014 Hwa Chia Chai et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Polymorphisms in genes involved in toll-like receptor/interferon signalling pathways have been reported previously to be associated with SLE in many populations. his study aimed to investigate the role of seven single nucleotide polymorphisms within TNFAIP3, STAT4, and IRF5, 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 of STAT4 rs7574865 and rs10168266 were associated with elevated risk of SLE in the Chinese and Malay patients, respectively ( = 0.028, odds ratio (OR) = 1.42;  = 0.035, OR = 1.80, respectively). Polymorphisms in TNFAIP3 and IRF5 did not show signiicant associations with SLE in any of the ethnicities. Combined analysis of the Malays, Chinese, and Indians for each SNP indicated that STAT4 rs10168266 was signiicantly associated with the Malaysian SLE as a whole ( = 0.014; OR = 1.435). he meta-analysis of STAT4 rs10168266, which combined the data of other studies and this study, further conirmed its importance as the risk factor for SLE by having pooled OR of 1.559 and  value of <0.001. 1. Introduction Systemic lupus erythematosus (SLE) is a prototypic autoim- mune disease afecting various parts of the body including skin, kidneys, lungs, joints, heart, nervous system, and hematopoietic organs. It is a disease whereby a diverse array of autoantibody production, complement activation, immune complex deposition, and inlammation cause dam- ages in those organs. Although the exact aetiology of SLE still remains unclear, a combination of genetic risk factors and environmental events is believed to contribute to an irreversible break in immunological self-tolerance. With the introduction of genome-wide association studies, a huge breakthrough has been made in the discovery of SLE asso- ciated susceptibility genes that in turn advances our under- standing of pathogenesis of SLE. Recently, several reviews have categorised the susceptible genes according to their immunological pathways and cell types. hree biological pathways involved in SLE have been forwarded by Harley et al. [1]: (i) innate immune response including toll-like recep- tor (TLR)/interferon (IFN) signalling pathways; (ii) adaptive immune response including B, T, and antigen-presenting cells immune signal transduction; and (iii) immune complex clearance mechanism. Defects in TLR/IFN signalling pathways cause immune complexes containing self-nucleic acids to interact with TLR7 and TLR9 inside plasmacytoid dendritic cells and B cells endosomes, resulting in the secretion of type I IFN and interleukin (IL)-6. he combined triggering of bothB cell receptors and TLR leads to autoreactive B-cell prolif- eration. heir further diferentiation into plasmablasts and autoantibody-secreting plasma cells is induced by type I IFN and IL-6, respectively [2]. TNFAIP3, STAT4, IRF5, TREX, and IRAK1 are the genes involved in upstream and downstream pathways of type I IFN production that have been recently identiied. he STAT4 gene consists of 24 exons that spread Hindawi Publishing Corporation Journal of Immunology Research Volume 2014, Article ID 529167, 9 pages http://dx.doi.org/10.1155/2014/529167