Non-inherited maternal human leukocyte antigen alleles in susceptibility to familial rheumatoid arthritis.
OBJECTIVE
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.
Guthrie
K A
KA
Clinical Statistics D5-360, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA. kguthrie@fhcrc.org
Tishkevich
N R
NR
Nelson
J L
JL
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D018604:Epitope Mapping / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009035:Mothers; D012306:Risk; D012737:Sex Factors
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C527195:HLA-DRB1*04 antigen