Association between PPP2CA polymorphisms and clinical features in southwest Chinese systemic lupus erythematosus patients.

Increasing evidence supports the involvement of a catalytic subunit (PP2Ac) of protein phosphatase 2A (PP2A) in the mechanisms of systemic lupus erythematosus (SLE). This study was conducted to explore the association single nucleotide polymorphisms (SNPs) of PPP2CA with SLE susceptibility, serum cytokines levels, and clinical features in a Chinese Han population. A case-control association study was carried out in 1509 Chinese Han subjects (730 SLE patients and 779 healthy individuals). Genotyping for genetic variants of PPP2CA (rs10491322 and rs7704116) was performed using a polymerase chain reaction-high resolution melting (PCR-HRM) assay. In the cohort of SLE patients, we observed that rs10491322 and rs7704116 were positively increased SLE susceptibility (OR = 1.61, 95% CI = 1.13-2.31, P = .009; OR = 1.59, 95% CI = 1.17-2.15, P = .003, respectively). Interestingly, the AG genotype of rs10491322 carriers presented higher IL-6 (P < .001) and IL-17 (P < .001) than those with AA genotype carriers. Specifically, carriage of the rs10491322 G* allele led to a higher prevalence of arthritis in SLE patients (P = .01). This study demonstrated an association of PPP2CA (rs10491322 and rs7704116) with SLE susceptibility in a Chinese Han population. Furthermore, the minor allele of PPP2CA rs10491322 as a risk factor was correlated with immunologic disorders for SLE.

Autoimmune disease associated IFIH1 single nucleotide polymorphism related with IL-18 serum levels in Chinese systemic lupus erythematosus patients.

Systemic lupus erythematosus (SLE) has heterogeneous clinical manifestations. IFIH1 (interferon induced with helicase C domain 1) as one of antiviral helicase genes mediating type I interferon production, plays an essential role in the pathogenesis of SLE. The gene variants in IFIH1 could abnormally activate antiviral defenses and increased type I interferon signaling. The present study aimed to validate associations between single nucleotide polymorphisms (SNP) in IFIH1 and the pathogenesis of SLE. In total, rs1990760, rs3747517 and rs10930046 in IFIH1 are genotyped in 400 SLE patients and 659 health controls in Chinese cohort by an improved multiplex ligation detection reaction (iMLDR) technique. Significant associations were observed between alleles of IFIH1 (rs1990760 C > T, P = 0.005, OR = 1.36, 95%CI = 1.10-1.69; rs3747517 T > C, P = 0.004, OR = 1.31, 95%CI = 1.09-1.58, respectively) and SLE susceptibility. IFIH1 rs1990760 TT genotype carriers had lower serum levels of IL-18 (P < 0.001) and granzyme B (P < 0.001) than CC and CT genotype carriers. IFIH1 rs1990760 CT genotype carriers had higher anti-dsDNA-positive than CC and TT genotype carriers. In conclusion, IFIH1 polymorphisms (rs1990760 and rs3747517) were associated with SLE susceptibility and rs1990760 risk T allele related with IL-18 and granzyme B serum levels in SLE patients.