Associated genetic polymorphisms and clinical manifestations in systemic lupus erythematosus in Asian populations - A systematic literature review

INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic and life-threatening autoimmune disease. Its prevalence and clinical manifestations are known to be particularly severe in the Asian populations. Although genetics is known to play an important role in SLE susceptibility and clinical manifestations, the specific polymorphisms associated with these phenotypes in Asia are unclear. Therefore, we aim to review the association of SLE genetic polymorphisms with lupus manifestations across Asian populations and their role in the pathogenesis of SLE.

METHODS: A systematic search was conducted on PubMed, EBSCOHost, and Web of Science. We identified 22 casecontrol studies that matched our inclusion and exclusion criteria. Information such as study characteristics, genetic polymorphisms associated with SLE, and organ manifestations was extracted and reported in this review.

RESULTS: In total, 30 polymorphisms in 16 genes were found to be associated with SLE among Asians. All included polymorphisms also reported associations with various SLE clinical features. The association of rs1234315 in TNFSF4 linking to SLE susceptibility (P=4.17x10-17 OR=1.45 95% CI=1.34-1.59) and musculoskeletal manifestation (P=3.35x10-9, OR=1.37, 95%CI= 1.23-1.51) might be the most potential biomarkers to differentiate SLE between Asian and other populations. In fact, these associated genetic variants were found in loci that were implicated in immune systems, signal transduction, gene expression that play important roles in SLE pathogenesis.

DISCUSSIONS AND CONCLUSIONS: This review summarized the potential correlation between 30 genetic polymorphisms associated with SLE and its clinical manifestations among Asians. More efforts in dissecting the functional implications and linkage disequilibrium of associated variants may be required to validate these findings.