[Association of the PADI4 gene polymorphism and HLA-DRB1 shared epitope alleles with rheumatoid arthritis].

OBJECTIVE

To investigate the association of single nucleotide polymorphisms (SNPs) of the peptidylarginine deiminase IV (PADI4) and HLA-DRB1 shared epitope (SE) alleles with rheumatoid arthritis(RA) in a Chinese population.

METHODS

Four exonic SNPs of the PADI4 gene (PADI 4_89A/G, PADI 4_90C/T, PADI 4_92C/G and PADI 4_104C/T) were genotyped in 67 unrelated patients with RA and 81 healthy controls, using cDNA sequencing and T vector cloning. HLA-DRB 1*01, *04 and *10 subtypes were determined by polymerase chain reaction with sequence specific primers (PCR-SSP).

RESULTS

The distributions of the 4 SNPs were different in the two groups, and increased RA susceptibility was significantly associated with the minor alleles of PADI 4_89G (P was 0.023), PADI 4_90T (P was 0.004), PADI 4_104T (P was 0.003), and the haplotypes carrying the 4 minor alleles (P was 0.008). HLA-DRB1 SE alleles are composed of HLA-DRB 10101, *0102, *0401, *0404, *0405, *0408, *0409, *0410 and *1001. Individuals carrying the SE alleles were associated with increased RA susceptibility (P was 0.002). Individuals carrying both the SE alleles and minor alleles of the 4 SNPs were more susceptible to RA than individuals carrying neither the minor SNP alleles nor the SE alleles.

CONCLUSION

The PADI4 SNPs and haplotypes are associated with RA susceptibility in Chinese. HLA-DRB1 shared epitope is also an important risky factor for RA. There may exist certain synergistic effect between the PADI4 minor alleles and the HLA-DRB1 shared epitope.