Funding from NIAMS RFA (AR-93-006) on Lupus in Women and Minorities made possible the collection of African-American pedigrees who were multiplex for systemic lupus erythematosus and the performance of a genome scan. In the first 31 pedigrees, we have found at least seven potential linkages which are relatively specific for lupus in African-Americans. Of these, the FcgammaRIIA locus provides the most consistent evidence for linkage with a lod score of 3.37 and a possibly significant affected sib-pair analysis (p=0.0005). The affected sib-pairs provide broad support for linkage from five of the surrounding loci spanning approximately 35 cM. D1s3462 also has suggestive evidence for linkage at lod=3.50. Five other loci obtain lod greater than 1.5 (D11s2002, D11s1392 and D3s1766) or p less than 0.01 by two applied allele sharing algorithms (D3s1053 and D17s2180) and have an effect which is predominately in the African-American pedigrees. Three additional loci appear to have effects found in families multiplex for lupus of both African and European origin (lod=2 to 2.5). We are resubmitting this proposal in order to obtain the resources with which to continue this work.
Our specific aims for the coming funding period are: 1. To enlarge the collection of African-American pedigrees multiplex for lupus, 2. To convincingly establish linkage and pursue the identity of the genes responsible near FcgammaRIIA and D1s3462, 3. To establish the presence of other linkages with lupus in African-American pedigrees, 4. To evaluate other phenotype definitions by examining their relationship with the linkages established, and 5. To explore the criteria for lupus and the antinuclear antibody titer as quantitative trait phenotypes in these families. Results from this study are likely to contribute to understanding the genetics of systemic lupus erythematosus in African-Americans.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
3R01AR042460-07S1
Application #
6314344
Study Section
Special Emphasis Panel (ZRG1 (02))
Program Officer
Serrate-Sztein, Susana
Project Start
1993-09-30
Project End
2004-05-31
Budget Start
2000-06-01
Budget End
2001-05-31
Support Year
7
Fiscal Year
2000
Total Cost
$124,205
Indirect Cost
Name
Oklahoma Medical Research Foundation
Department
Type
DUNS #
937727907
City
Oklahoma City
State
OK
Country
United States
Zip Code
73104
Deng, Yun; Zhao, Jian; Sakurai, Daisuke et al. (2016) Decreased SMG7 expression associates with lupus-risk variants and elevated antinuclear antibody production. Ann Rheum Dis 75:2007-2013
Zhao, Jian; Giles, Brendan M; Taylor, Rhonda L et al. (2016) Preferential association of a functional variant in complement receptor 2 with antibodies to double-stranded DNA. Ann Rheum Dis 75:242-52
Liu, Ke; Kurien, Biji T; Zimmerman, Sarah L et al. (2016) X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased Prevalence of 47,XXX in Systemic Lupus Erythematosus and Sjögren's Syndrome. Arthritis Rheumatol 68:1290-1300
Kariuki, S N; Ghodke-Puranik, Y; Dorschner, J M et al. (2015) Genetic analysis of the pathogenic molecular sub-phenotype interferon-alpha identifies multiple novel loci involved in systemic lupus erythematosus. Genes Immun 16:15-23
Lu, Xiaoming; Zoller, Erin E; Weirauch, Matthew T et al. (2015) Lupus Risk Variant Increases pSTAT1 Binding and Decreases ETS1 Expression. Am J Hum Genet 96:731-9
Kottyan, Leah C; Zoller, Erin E; Bene, Jessica et al. (2015) The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share. Hum Mol Genet 24:582-96
Zhao, Jian; Wu, Hui; Langefeld, Carl D et al. (2015) Genetic associations of leptin-related polymorphisms with systemic lupus erythematosus. Clin Immunol 161:157-62
Armstrong, D L; Zidovetzki, R; Alarcón-Riquelme, M E et al. (2014) GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region. Genes Immun 15:347-54
Morris, D L; Fernando, M M A; Taylor, K E et al. (2014) MHC associations with clinical and autoantibody manifestations in European SLE. Genes Immun 15:210-7
Guthridge, Joel M; Lu, Rufei; Sun, Harry et al. (2014) Two functional lupus-associated BLK promoter variants control cell-type- and developmental-stage-specific transcription. Am J Hum Genet 94:586-98

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