RESEARCH - Influence of male sex on disease phenotype in familial RA

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Arthritis Rheum. 2006 Sep 28;54(10):3087-3094 [Epub ahead of print]

Influence of male sex on disease phenotype in familial rheumatoid arthritis.

Jawaheer D, Lum RF, Gregersen PK, Criswell LA.

University of California, Los Angeles.

OBJECTIVE: To examine sex differences in clinical, demographic, and genetic

characteristics among a large cohort of patients with familial rheumatoid

arthritis (RA). METHODS: We studied 1,004 affected members of 467 Caucasian

multicase RA families recruited from the North American Rheumatoid Arthritis

Consortium. Standardized information about demographic and clinical

characteristics was collected from all patients. Affected individuals also

underwent radiography of the hands and were genotyped for markers in the HLA

region. Sex differences were assessed using contingency table analysis (for

categorical variables) and Student's t-tests for (continuous variables), and

by multivariate logistic and linear regression analysis. RESULTS: Male

patients had a significantly later onset of RA, were more likely to be

seropositive for RF, and had significantly higher titers of anti-cyclic

citrullinated peptide (anti-CCP) antibodies compared with female patients,

even after adjustment for covariates in multivariate analyses. Male patients

were also significantly more likely to have a history of smoking and to be

HLA-DRB1 shared epitope (SE) positive. Interestingly, female patients with

an affected male sibling had significantly higher titers of anti-CCP

antibodies and were more likely to be SE positive compared with female

patients without affected male siblings. Multivariate analyses indicated

that the presence of the SE did not fully explain the increased anti-CCP

antibody titers observed in these families.

CONCLUSION: Sex has an important influence on the disease phenotype in RA,

including the age at disease onset and autoantibody production. Furthermore,

families with affected male members are characterized by higher titers of

autoantibodies, particularly anti-CCP antibodies. Our results indicate that

these findings are not fully explained by differences in exposure to tobacco

smoke, presence of the HLA-DRB1 SE, or other HLA region genetic variation.

Thus, other genetic or nongenetic factors also contribute to sex differences

in the RA phenotype.

PMID: 17009227

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

7009227

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