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

Abstract

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_89*A/G, PADI 4_90*C/T, PADI 4_92*C/G and PADI 4_104*C/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_89*G (P was 0.023), PADI 4_90*T (P was 0.004), PADI 4_104*T (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 1*0101, *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.

• Authors: Lie-ying Fan, Ming Zong, Tian-bao Lu, Lin Yang, Yuan-yuan Ding, Jian-wei Ma
• Journal: Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics (Zhonghua Yi Xue Yi Chuan Xue Za Zhi) Vol. 26 Issue 1 Pg. 57-61 (Feb 2009) ISSN: 1003-9406 [Print] China
• PMID: 19199253 (Publication Type: Journal Article)

Chemical References

• Epitopes
• HLA-DR Antigens
• HLA-DRB1 Chains
• Hydrolases
• PADI4 protein, human
• Protein-Arginine Deiminase Type 4
• Protein-Arginine Deiminases

Topics

• Adult
• Aged
• Aged, 80 and over
• Alleles
• Arthritis, Rheumatoid (genetics)
• Asian People (genetics)
• Case-Control Studies
• Epitopes (genetics)
• Female
• Gene Frequency
• Genetic Predisposition to Disease
• HLA-DR Antigens (genetics)
• HLA-DRB1 Chains
• Humans
• Hydrolases (genetics)
• Male
• Middle Aged
• Phenotype
• Polymorphism, Single Nucleotide
• Protein-Arginine Deiminase Type 4
• Protein-Arginine Deiminases