The overall objective of this application for a Small Research Grant is to elucidate additional genetic factors that explain the excess risk of lupus associated with gender and ethnicity. The first specific aim is to determine if androgen receptor (AR) gene polymorphisms are associated with a risk for systemic lupus erythematosus (SLE). The investigator will test the hypotheses that the androgen receptor (AR) gene confers susceptibility to SLE and that nonrandom x-inactivation alone or in combination with maternal x transmission distortion is more common in lupus families. The second specific aim is to determine if AR gene polymorphisms are associated with the response to the weak androgen DHEA. The investigator will test the hypotheses that the AR gene modulates the response to DHEA and that the AR genotype is associated with variation in estradiol metabolism. The principal investigator is Patricia Fraser, M.D, Assistant Professor of Medicine at Harvard Medical School and Program Director of the Juvenile and Adolescent Rheumatology Program at the Brigham Arthritis Center. Robert Lahita, M.D., Ph.D., Associate Professor and Chief of the Division of Rheumatology at Columbia University, will provide samples. David Bing, Ph.D., Director of Clinical Research Testing at CRB Labs in Boston, will collaborate in data analysis.
| Rajsbaum, R; Fici, D; Fraser, P A et al. (2001) Polymorphism of the human retinoid X receptor beta and linkage disequilibrium with HLA-DPB1. Tissue Antigens 58:24-9 |
| Barsky, A J; Orav, E J; Ahern, D K et al. (1999) Somatic style and symptom reporting in rheumatoid arthritis. Psychosomatics 40:396-403 |
| Fraser, P A; Lu, L Y; DeCeulaer, K et al. (1999) CD4 TCRBV CDR3 analysis in prevalent SLE cases from two ethnic groups. Lupus 8:311-9 |
| Clavijo, O P; Delgado, J C; Yu, N et al. (1999) HLA-Cw*1701 is associated with two sub-Saharan African-derived HLA haplotypes: HLA-B*4201, DRB1*03 and HLA-B*4202 without DRB1*03. Tissue Antigens 54:303-6 |
| Uko, G P; Lu, L Y; Asuquo, M A et al. (1999) HLA-DRB1 leprogenic motifs in nigerian population groups. Clin Exp Immunol 118:56-62 |
| Bae, S C; Fraser, P; Liang, M H (1998) The epidemiology of systemic lupus erythematosus in populations of African ancestry: a critical review of the ""prevalence gradient hypothesis"". Arthritis Rheum 41:2091-9 |
