Association of miR-181 cluster polymorphisms with systemic lupus erythematosus risk

Systemic lupus erythematosus (SLE) is an autoimmune disease manifested by self-reactive antibodies due to failure of selection in both B and T lymphocytes. miR-181, expressed in hematopoietic cell lineage, has been proven to be an important modulator of Band T-cell differentiation, maturation, and function. This study aimed to investigate association of three polymorphisms (rs16927589 T>C, rs77418916 A>T, and rs8108402 C>T) of the miR-181 cluster with risk of SLE in a Chinese population. In this study, 202 patients with SLE and 299 control subjects were included. miR-181 polymorphisms were discriminated by Snapshot SNP genotyping assay and DNA sequencing methods. It was found that T allele, TT, and TC genotypes, and the TT/CT vs. CC and CC/CT vs. TT models of rs8108402 C>T polymorphism were associated with increased risk of SLE (T vs. C: adjusted OR=1.51, 95% CI: 1.13~2.00, P=0.005; TT vs. CC: adjusted OR=2.65, 95% CI: 1.18~5.98, P=0.019; TC vs. CC: adjusted OR=1.50, 95% CI, 1.03~2.19, P=0.033; TT/CT vs. CC: adjusted OR=1.61, 95% CI: 1.12~2.31, P=0.010; CC/CT vs. TT: adjusted OR=2.23, 95% CI: 1.01~4.93, P=0.048). Haplotype analysis showed that TAT haplotype was associated with increased risk of SLE (OR=1.48, 95% CI: 1.09~2.00, P=0.011), while TAC haplotype was associated with decreased risk of SLE (OR=0.68, 95% CI: 0.53~0.89, P=0.004). However, significant association between the other two polymorphisms and SLE risk was not observed. In conclusion, for the first time, it was found that rs8108402 C>T polymorphism is associated with increased risk of SLE, in a Chinese population.