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

Guthrie, Katherine A. and Tishkevich, Natalia R. and Nelson, J. Lee (2009) Non-inherited maternal human leukocyte antigen alleles in susceptibility to familial rheumatoid arthritis. Annals of the rheumatic diseases, 68 (1). pp. 107-109. ISSN 1468-2060

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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.

Item Type: Article or Abstract
Additional Information: The final published version of this article is available to subscribers only via the URL above.
DOI: 10.1136/ard.2008.092312
PubMed ID: 18684745
NIHMSID: 135329
PMCID: PMC2760537
Grant Numbers: R01 AI041721-12, R01 AI045659-10
Keywords or MeSH Headings: Adolescent; Adult; Age of Onset; Aged; Alleles; Arthritis, Rheumatoid/genetics/immunology; Child; Child, Preschool; Epitope Mapping/methods; Female; Genetic Predisposition to Disease; Genotype; HLA-DR Antigens/genetics; Humans; Logistic Models; Male; Middle Aged; Mothers; Risk; Sex Factors;
Subjects: Diseases > Autoimmune
Diseases > Hereditary Diseases
Research Methodologies > Epidemiology > Risk assessment
Molecules > Antigens > HLA antigens
Depositing User: Library Staff
Date Deposited: 28 Jul 2009 20:51
Last Modified: 14 Feb 2012 14:42

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