Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Sex-Specific Genetic Architecture of Systemic Lupus Erythematosus.
Sawalha1, Amr H., Richardson14, Bruce C., Harley13, John B., Scofield12, Robert H., James11, Judith A., Alarcon-Riquelme10, Marta E., Vyse9, Tomothy J.
Oklahoma Medical Research Foundation, Oklahoma City, OK
Oklahoma Medical Research Foundation, Center for Genomics and Oncological Research Pfizer-University of Granada-Junta de Andalucia, Oklahoma City, OK
Oklahoma Medical Research Foundation and Oklahoma University Health Sciences Center, Oklahoma City, OK
Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, US Department of Veterans Affairs Medical Center and Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK
Cincinnati Children's Hospital Medical Center and the US Department of Veterans Affairs Medical Center, Cincinnati, OH
University of Michigan, Ann Arbor, MI
Oklahoma Medical Research Foundation, Oklahoma CIty, OK
Wake Forest University, Winston-Salem
Wake Forest University Health Sciences, Winston-Salem, NC
Division of Rheumatologyand Immunology, Medical University of South Carolina, Charleston, SC
Instituto de Parasitologia y Biomedicina Lopez-Neyra (CSIC), Granada, Spain
Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK
King's College London, Guy's Hospital, London, United Kingdom
Systemic lupus erythematosus 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 lupus is not clearly defined. Here, we examine sex-specific genetic effects among lupus-susceptibility loci.
A total of 18 lupus-associated autosomal genetic loci were genotyped in a large set of lupus patients and controls of European descent, consisting of 5,932 female and 1,495 male samples. Sex-specific genetic association analyses were performed. Sex-gene interaction was further validated using both a parametric (logistic regression) and non-parametric (multifactor dimensionality reduction) methods. We examined aggregate differences in sex-specific genetic risk by calculating a cumulative genetic risk score for lupus in each individual and comparing average genetic risk between men and women.
We observe a significantly higher cumulative genetic risk for lupus in men than in women. We report significant sex-gene interaction in the HLA region and IRF5 genes whereby male lupus patients possess a significantly higher frequency of risk alleles than their female counterparts. We also report that the genetic effect observed in KIAA1542 is specific to female lupus patients, and does not seem to play a role in lupus in men.
Our data indicate that men require a higher cumulative genetic load to develop lupus compared to women. This observation suggests that the higher prevalence of lupus in women, and the more severe lupus phenotype in men could be related to autosomal genes.
To cite this abstract, please use the following information:
Sawalha, Amr H., Richardson, Bruce C., Harley, John B., Scofield, Robert H., James, Judith A., Alarcon-Riquelme, Marta E., et al; Sex-Specific Genetic Architecture of Systemic Lupus Erythematosus. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :157