Epistatic effects occurring among susceptibility and protective MHC genes in IgA deficiency

Genes Immun. 2003 Jun;4(4):316-20. doi: 10.1038/sj.gene.6363955.


Immunoglobulin A deficiency (IgAD), the most prevalent primary immunodeficiency in Caucasian populations, shows strong evidence of polygenic inheritance with several associated genes being located in the major histocompatibility complex (MHC). Our aims were to determine which previously described MHC associations were primary and not secondary to a decrease or an increase in other MHC haplotype frequencies, to study the genetic interactions between all disease-associated MHC haplotypes and, finally, to ascertain the relative importance of protection vs susceptibility. A relative predispositional effect (RPE) study showed that in addition to the primary positive association of IgAD with HLA-DRB1*0102, DR3/TNFa2b3, and DR7 carrying haplotypes, DRB1*1501 was a marker of a primary protective factor in the Spanish population. Our data also indicate that the combined presence in an individual of two MHC susceptibility haplotypes notably increases the predisposition to the disease and that DRB1*1501 positive haplotypes eliminate the susceptibility conferred by any other MHC haplotype.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Chi-Square Distribution
  • Confidence Intervals
  • Epistasis, Genetic*
  • Gene Frequency / genetics
  • Genes, MHC Class II*
  • Genetic Predisposition to Disease*
  • Genotype
  • HLA-D Antigens / genetics*
  • Haplotypes / genetics
  • Humans
  • IgA Deficiency / genetics*
  • Odds Ratio


  • HLA-D Antigens