Single-nucleotide polymorphisms in the class II region of the major histocompatibility complex in Japanese patients with immunoglobulin A nephropathy

J Hum Genet. 2002;47(10):532-8. doi: 10.1007/s100380200080.


Immunoglobulin A nephropathy (IgAN) is a form of chronic glomerulonephritis of unknown etiology and pathogenesis. Immunogenetic studies have not conclusively indicated that human leukocyte antigen (HLA) is involved. As a first step in investigating a possible relationship between HLA class II genes and IgAN, we analyzed the extent of linkage disequilibrium (LD) in this region of chromosome 6p21.3 in a Japanese test population and found extended LD blocks within the class II locus. We designed a case-control association study of single-nucleotide polymorphisms (SNPs) in each of those LD blocks, and determined that SNPs located in the HLA- DRA gene were significantly associated with an increased risk of IgAN ( P = 0.000001, odds ratio = 1.91 [95% confidence interval 1.46-2.49]); SNPs in other LD blocks were not. Our data imply that some haplotype of the HLA- DRA locus has an important role in the development of IgAN in Japanese patients.

Publication types

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

MeSH terms

  • Adult
  • Alleles
  • Case-Control Studies
  • Chromosomes, Human, Pair 6 / genetics
  • Female
  • Genes, MHC Class II / genetics*
  • Genetic Predisposition to Disease
  • Genotype
  • Glomerulonephritis, IGA / genetics*
  • HLA-DR Antigens / genetics*
  • HLA-DR alpha-Chains
  • Humans
  • Japan
  • Linkage Disequilibrium / genetics
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide / genetics*


  • HLA-DR Antigens
  • HLA-DR alpha-Chains