期刊
ANNALS OF THE RHEUMATIC DISEASES
卷 71, 期 5, 页码 694-699出版社
B M J PUBLISHING GROUP
DOI: 10.1136/annrheumdis-2011-200385
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资金
- Lupus Foundation of America
- NIH
- Arthritis National Research Foundation
- American College of Rheumatology/Research and Education Foundation
- Lupus Research Institute
- Kirkland Scholar awards
- Alliance for Lupus Research
- US Department of Veterans Affairs
- US Department of Defense [PR094002]
- European Science Foundation [07-RNP-083]
- Swedish Research Council
- Instituto de Salud Carlos III [PS09/00129]
- European Union
- Consejeria de Salud de Andalucia [PI0012]
Objectives Systemic lupus erythematosus (SLE) is a sexually dimorphic autoimmune disease which is more common in women, but affected men often experience a more severe disease. The genetic basis of sexual dimorphism in SLE is not clearly defined. A study was undertaken to examine sex-specific genetic effects among SLE susceptibility loci. Methods A total of 18 autosomal genetic susceptibility loci for SLE were genotyped in a large set of patients with SLE and controls of European descent, consisting of 5932 female and 1495 male samples. Sex-specific genetic association analyses were performed. The sex-gene interaction was further validated using parametric and nonparametric methods. Aggregate differences in sex-specific genetic risk were examined by calculating a cumulative genetic risk score for SLE in each individual and comparing the average genetic risk between male and female patients. Results A significantly higher cumulative genetic risk for SLE was observed in men than in women. (P=4.52x10(-8)) A significant sex-gene interaction was seen primarily in the human leucocyte antigen (HLA) region but also in IRF5, whereby men with SLE possess a significantly higher frequency of risk alleles than women. The genetic effect observed in KIAA1542 is specific to women with SLE and does not seem to have a role in men. Conclusions The data indicate that men require a higher cumulative genetic load than women to develop SLE. These observations suggest that sex bias in autoimmunity could be influenced by autosomal genetic susceptibility loci.
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