Journal
ANNALS OF THE RHEUMATIC DISEASES
Volume 68, Issue 1, Pages 107-109Publisher
B M J PUBLISHING GROUP
DOI: 10.1136/ard.2008.092312
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Funding
- US National Institutes of Health [N01 AR22263, AI45659, AI41721]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI045659, R01AI041721] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [N01AR022263] Funding Source: NIH RePORTER
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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 >= 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.
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