rs2240340

This case-control association study examined five PADI4 SNPs (rs11203366, rs11203367, rs874881, rs2240340, rs1748033) in 378 Chinese Han RA patients versus 204 controls. While PADI4-92 (rs874881) showed a statistically significant genotype difference (χ²=12.07, p=0.0024) with a protective effect (OR<1), overall PADI4 polymorphisms were not significantly associated with RA susceptibility in this population, contrasting with positive findings in Japanese and Korean populations.

A case-control study of 1,123 Korean rheumatoid arthritis patients and 1,008 controls found that genetic variants at PTPN22, TRAF1/C5, 6q23, 4q27, CD40, and CCL21 previously associated with Caucasian RA were not associated with Korean RA. The PADI4 variant rs2240340 showed strong association (p=1.15×10⁻⁸, OR=1.43), demonstrating substantial genetic heterogeneity between ethnic populations.

A two-stage genome-wide association study (GWAS) in Spanish population identified KLF12 as a new susceptibility locus for rheumatoid arthritis, with rs1324913 showing stronger association (P=0.01) in replication than PTPN22 rs2476601. Joint analysis with three previous GWAS studies confirmed KLF12 and PTPRT as commonly associated loci, with KLF12 SNP rs1887346 and rs9318228 showing P values of 6.03×10⁻⁵ and 3.66×10⁻⁵ in the discovery phase and evidence of replication across multiple populations.