Non-inherited maternal human leukocyte antigen alleles in susceptibility to familial rheumatoid arthritis

Ann Rheum Dis. 2009 Jan;68(1):107-9. doi: 10.1136/ard.2008.092312. Epub 2008 Aug 6.

Abstract

Objectives: Some patients with rheumatoid arthritis (RA) lack RA-associated human leukocyte antigen (HLA) alleles. Prior studies investigated non-inherited maternal HLA alleles (NIMA) in RA risk with conflicting results.

Methods: We examined NIMA in a large cohort of families from the North American Rheumatoid Arthritis Consortium (NARAC).

Results: Among 620 patients with 1 or both parents having a HLA genotype, patients with RA informative for analysis included 176 without HLA-DRB1*04 and 86 without the HLA shared epitope (SE). The frequency of NIMA encoding HLA-DR4 or the SE was compared to the non-inherited paternal allele (NIPA). DR4-encoding NIMA vs NIPA revealed no significant difference (27% vs 20%). However, parity is known to modulate RA risk and analyses stratified by sex and age of onset showed significant variation among women. Interestingly, among women with onset <45 years DR4-encoding NIMA was increased compared to NIPA; among women > or =45 years at onset the reverse was observed (31% vs 16% compared to 10% vs 60%, p = 0.008). DR4 encoding NIMA vs NIPA did not differ in men. The SE did not differ in men or women.

Conclusions: Risk of RA was associated with HLA-DR4 encoding NIMA in younger-onset women but not in older-onset women or men. These observations could help explain conflicting prior results of NIMA in RA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Aged
  • Alleles
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / immunology*
  • Child
  • Child, Preschool
  • Epitope Mapping / methods
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • HLA-DR Antigens / genetics*
  • HLA-DRB1 Chains
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Mothers*
  • Risk
  • Sex Factors

Substances

  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • HLA-DRB1*04 antigen