Variants in TNFSF4, TNFAIP3, TNIP1, BLK, SLC15A4 and UBE2L3 interact to confer risk of systemic lupus erythematosus in Chinese population

Our previous genome-wide association studies on SLE have identified several susceptibility genes involved in NF-kappa B signaling pathway, including TNFSF4, TNFAIP3, TNIP1, BLK, SLC15A4 and UBE2L3. The aim of this study is to investigate the association model (additive, dominant, recessive) of these genes and search for possible gene-gene interactions between them. In this study, we explored the association model of these six genes and search for possible gene-gene interactions based on identified single-nucleotide polymorphisms (SNPs) among them by using logistic regression analysis in the combined sample of 4,199 cases and 8,255 controls. The most significant association evidence was observed under recessive model for all of these SNPs. Besides, significant interactions between these SNPs were observed in this study: the TNFSF4 and TNIP1 SNPs (P (adjusted) = 1.68E-10), the TNFSF4 and SLC15A4 SNPs (P (adjusted) = 3.55E-08), the TNFSF4 and UBE2L3 SNPs (P (adjusted) = 8.74E-13), the TNIP1 and BLK SNPs (P (adjusted) = 9.45E-10), the TNIP1 and UBE2L3 SNPs (P (adjusted) = 8.25E-11), the TNFAIP3 and UBE2L3 SNPs (P (adjusted) = 3.06E-14) and the BLK and SLC15A4 SNPs (P (adjusted) = 4.51E-12). These results may contribute to our understanding of SLE genetic interactions and account for the additional risk of certain patients to develop SLE.