Analysis of a genome-wide association study-linked locus (CCR6) in Asian rheumatoid arthritis

DNA Cell Biol. 2012 Apr;31(4):607-10. doi: 10.1089/dna.2011.1350. Epub 2011 Nov 17.

Abstract

A genome-wide association study in Japan identified the C-C chemokine receptor type 6 gene (CCR6) as associated with rheumatoid arthritis (RA). This finding has not been validated in other Asian populations. A case-control study involving 996 subjects, comprising 440 controls and 556 RA patients, was done to determine their anticyclic citrullinated peptide (anti-CCP) antibody status and CCR6 polymorphism (rs3093024) genotype. Three hundred eighty-seven patients were anti-CCP positive and 153 anti-CCP negative. Logistic regression showed that allele A was likely to increase the risk of developing RA among females via a recessive model (odds ratio [OR]=1.55, 95% confidence interval [CI]=1.01, 2.39), whereas the risk effect appeared to be reduced among males via an additive model (OR=0.60, 95% CI=0.42, 0.85). Considering only subjects who are anti-CCP positive, allele A increased RA risk among females via a recessive model (OR=1.68, 95% CI=1.07, 2.64) but decreased the risk among males via an additive model (OR=0.59, 95% CI=0.39, 0.89). We showed that CCR6 polymorphism was a risk factor among females but a protective factor among males. Functional studies are warranted to unravel the pathophysiological relevance of the gene variant and other linked variants with RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / epidemiology
  • Arthritis, Rheumatoid / genetics*
  • Asian People / genetics*
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Japan / epidemiology
  • Logistic Models
  • Male
  • Models, Genetic
  • Odds Ratio
  • Receptors, CCR6 / genetics*
  • Risk Factors
  • Sex Factors

Substances

  • CCR6 protein, human
  • Receptors, CCR6