Micro-RNA-146A Is Associated With Susceptibility To Systemic Lupus Erythematosus In Chinese Han Population

Background Systemic lupus erythematosus (SLE) is an autoimmune disease with various clinical manifestations, involving multiple systems. The pathogenesis has not been entirely cleared. SLE is a polygenic disease, which is related with genetic, immune, viral infections, drugs, hormones and so on. Genetic factor may play an important role in the pathogenesis of SLE. In the past two decades, many groups had mainly revealed of susceptibility genes by genome-wide scanning and candidate gene study, but most results were not consistent. Online Mendelian Inheritance in Man (OMIM) embodies 13 SLE susceptibility loci. There are 11 loci which have found by linkage analysis and genome-wide scan: 1q41-42 (SLEB1), 2q37.3 (SLEB2), 4p16-15.2 (SLEB3), 12q24 (SLEB4), 13q32 (SLEB5), 16q11.2 (SLEB6), 20p12 (SLEB7), 20q13.1 (SLEB8),1q32 (SLEB9), 7q32(SLEB10), 2q32.2-q32.3(SLEB11). We had found a number of susceptibility genes by fine mapping and candidate gene approach, for example: PTPN22, CRP, FCGR2A, FCGR3A, FCGR2B, STAT4, IRF5, TLR5, ITGAM-ITGAX, FAS, PARP, PDCD1, HLA-DRB1, C2 and C4.In recent years, as The International HapMap Project had finished and lower-cost, highly efficient and high-throughput genotyping technologies were appeared, the way of searching for the susceptibility gene of complexity disease in the level of genome-wide has become possible. It was also called Genome-wide association study (GWAS).This method has become the most effective method to study complex disease. So far, there are many GWAS about SLE. Harley et al had reported that the single nucleotide polymorphism (SNP) rs2431697 on 5q33.3 has been shown to be associated with SLE in European populations(P = 1.00×10-10,OR= 1.22). Since the genetic heterogeneity between ethnic populations has been suggested to be important in SLE risk, further research is also warranted to determine whether it is also involved in SLE in other populations. Here, the SNP rs2431697 was genotyped in a total of 1993 SLE patients and 4770 healthy controls of Chinese Han.In order to investigate the association between rs2431697 and SLE in Chinese Han population, Moreover, we further explored the susceptibility gene of SLE within 5q33.3 region by investigating the patterns of recombination and linkage disequilibrium (LD) around the risk-associated SNP rs2431697.Objective To investigate the association between rs2431697 and SLE in Chinese Han population. Explored the susceptibility gene of SLE within 5q33.3 region.Methods We genotyped the SNP rs2431697 on 5q33.3 in our study, which was performed in 1993 SLE cases and 4770 controls by using the Sequenom MassArray system., then we selected genotyping data of SNP rs2431697. Statistical analysis was performed by the MassArray Typer software. Investigating the patterns of recombination and linkage disequilibrium (LD) around the risk-associated SNP rs2431697.Results The SNP rs2431697 was highly associated with SLE in Chinese Han population [P= 6.27×10-11, odds ratio (OR) = 1.43, 95% confidence interval (95% CI):1.28-1.59]. In contrast to the European populations, the SNP rs2431697 has a higher risk allele frequency (Chinese Hans 87.16% versus Europeans 61.52%) and a stronger strength of association (OR :Chinese Hans 1.43 versus Europeans 1.22) in Chinese Han population. The SNP rs2431697 association signal lies in a ~100-kb LD block that contains only one gene MicroRNA-146a (MIR146A).Conclusion The SNP rs2431697 on 5q33.3 was associated with SLE in Chinese Han population, The MIR146A might be a susceptibility gene for SLE in Chinese Han population.