Newly identified genetic risk variants for celiac disease related to the immune response

Nat Genet. 2008 Apr;40(4):395-402. doi: 10.1038/ng.102. Epub 2008 Mar 2.

Abstract

Our genome-wide association study of celiac disease previously identified risk variants in the IL2-IL21 region. To identify additional risk variants, we genotyped 1,020 of the most strongly associated non-HLA markers in an additional 1,643 cases and 3,406 controls. Through joint analysis including the genome-wide association study data (767 cases, 1,422 controls), we identified seven previously unknown risk regions (P < 5 x 10(-7)). Six regions harbor genes controlling immune responses, including CCR3, IL12A, IL18RAP, RGS1, SH2B3 (nsSNP rs3184504) and TAGAP. Whole-blood IL18RAP mRNA expression correlated with IL18RAP genotype. Type 1 diabetes and celiac disease share HLA-DQ, IL2-IL21, CCR3 and SH2B3 risk regions. Thus, this extensive genome-wide association follow-up study has identified additional celiac disease risk variants in relevant biological pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers*
  • Case-Control Studies
  • Celiac Disease / genetics*
  • Celiac Disease / immunology
  • Chromosome Mapping
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / genetics
  • Female
  • Genetic Markers / genetics*
  • Genetic Predisposition to Disease*
  • Genome, Human*
  • HLA-DQ Antigens / metabolism
  • Humans
  • Interleukin-12 Subunit p35 / genetics
  • Interleukin-18 Receptor beta Subunit / blood
  • Interleukin-18 Receptor beta Subunit / genetics
  • Linkage Disequilibrium
  • Male
  • Mice
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • RGS Proteins / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, CCR3 / genetics
  • Risk Factors
  • Tissue Distribution

Substances

  • Biomarkers
  • Genetic Markers
  • HLA-DQ Antigens
  • IL12A protein, human
  • IL18RAP protein, human
  • Interleukin-12 Subunit p35
  • Interleukin-18 Receptor beta Subunit
  • RGS Proteins
  • RGS1 protein, human
  • RNA, Messenger
  • Receptors, CCR3