Association between FcgammaReceptor and IL-10 gene with SLE disease in Thai population

Abstract

Systemic lupus Erythematosus (SLE) is a prototype of systemic autoimmune disease. However, etiology of disease remains unclear. Consideral evidence suggests that SLE is a complex disease with a strong genetic basis, contributed from multiple genes as well as environmental factors. Genetic studies in both murine and human supported the importance of chromosome 1, in which several candidate genes were reported. For example, FcgammaRIIa plays a vital role in immune complex clearance and IL-10 promotes B cell hyperactivity leading to autoantibody production. Since polymorphisms in FcgammaRIIa and IL10 gene may affect to the binding capacity and a quantity of cytokine production, respectively. The aim of this study was to identify the polymorphisms of FcgammaRIIA and IL-10 genes in patient with SLE compared with control group and to determine the association with disease susceptibility and/or severity of SLE in Thai population. This population-based case-control study included 150 SLE patients and 150 healthy control subjects with similar ethnic and genetic background. FcgammaRIIa and IL-10 gene polymorphisms were identified by PCR-sequence specific primer (SSP) and PCR-restriction fragment length polymorphism (RFLP), respectively. The result of this study demonstrated that FcgammaRIIa R131 and ACC haplotype of IL10 were found to be significantly increased in SLE patients compared to healthy controls (OR= 1.57, 95%CI= 1.08-2.27, p= 0.01 and OR= 1.57, 95%CI= 1.05-2.34, p= 0.02, respectively). Importantly, for the first time, synergistic between ACC haplotype and R allele in susceptible to SLE was observed (OR= 10.93, 95%CI= 1.29-242.64, p= 0.006). In addition, there was an association between IL-10, GCC haplotype and renal involement (OR =7.45, 95%CI= 1.04-154.1, p = 0.02). FcgRIIa, RR homozygotes was also associated with anticardiolipin antibodies production (OR=6.09, 95%CI= 1.38-30.54, p= 0.004). In conclusion, ACC haplotype of IL-10 gene and FcgammaRIIa R131 polymorphism might be regarded as marker for genetic susceptibility to SLE in Thai population, particularly individuals carrying both of them. Severity of disease, such as lupus nephritis can be predicted by IL-10, GCC haplotype marker and anticardiolipin antibodies production can be predicted in FcgammaRIIa, RR homozygotes in SLE patient.