Contribution of an adenine to guanine single nucleotide polymorphism of the matrix metalloproteinase-13 (MMP-13) -77 promoter region to the production of anticyclic citrullinated peptide antibodies in patients with HLA-DRB1*shared epitope-negative rheumatoid arthritis

Mod Rheumatol. 2011 Jun;21(3):240-3. doi: 10.1007/s10165-010-0375-6. Epub 2010 Nov 26.

Abstract

We examined whether matrix metalloproteinase-13 (MMP-13) contributes to disease susceptibility or severity of rheumatoid arthritis (RA). Eighty-seven patients with RA whose disease duration was <2 years and 71 healthy controls were enrolled in the study. Adenine (A) to guanine (G) single nucleotide polymorphism (SNP) of the -77 MMP-13 promoter region in RA and healthy controls was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Human leukocyte antigen (HLA)-DRB1 genotyping was also performed using the same populations. Anticyclic citrullinated peptide (anti-CCP) antibodies from RA patients at entry were studied, and their relationships were examined. The genotype and allele frequency of SNP of MMP-13 at -77 did not differ between RA patients and healthy controls. We focused on the RA patients who were negative for HLA-DRB1*shared epitope (SE) alleles and found that the seropositivity of anti-CCP antibodies with a titer >25 U/ml was high in the A/A genotype compared with the G/G genotype. The same characteristic was also found in HLA-DRB1*0405 allele-negative patients. Our data suggest that SNP of the -77 MMP-13 promoter region acts as a surrogate marker of anti-CCP antibody production in HLA-DRB1*SE allele-negative RA patients, which may reflect RA severity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / ethnology
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / immunology*
  • Asian People / genetics
  • Asian People / statistics & numerical data
  • Autoantibodies / genetics*
  • Autoantibodies / immunology
  • Epitopes / genetics
  • Epitopes / immunology
  • Female
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • HLA-DR Antigens / genetics*
  • HLA-DR Antigens / immunology
  • HLA-DRB1 Chains
  • Humans
  • Japan / epidemiology
  • Male
  • Matrix Metalloproteinase 13 / genetics*
  • Matrix Metalloproteinase 13 / immunology
  • Middle Aged
  • Peptides, Cyclic / immunology*
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic / genetics
  • Risk Factors
  • Severity of Illness Index

Substances

  • Autoantibodies
  • Epitopes
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Peptides, Cyclic
  • cyclic citrullinated peptide
  • MMP13 protein, human
  • Matrix Metalloproteinase 13