Abstract

Evidence indicates that SLE is polygenic, and it has been speculated that individual mutated genes may contribute to specific features of the disease. IL-21 is a type I cytokine that plays important roles in the differentiation of B cells into plasma cells, in dendritic cell maturation, and in T cell responses. IL-21 is therefore an attractive candidate gene for SLE. Preliminary studies strongly suggest that IL-21 is polymorphic in patients with SLE. The hypothesis to test is that IL-21 polymorphisms are associated with functional consequences that increase the susceptibility to SLE.
Two specific aims are proposed: 1) characterize the polymorphisms and haplotypes of IL-21 that cause SLE susceptibility, and 2) determine the functional consequences of IL-21 polymorphisms upon SLE susceptibility.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Research Grants (R03)
Project #
5R03AI076729-02
Application #
7642427
Study Section
Arthritis, Connective Tissue and Skin Study Section (ACTS)
Program Officer
Johnson, David R
Project Start
2008-06-20
Project End
2011-05-31
Budget Start
2009-06-01
Budget End
2011-05-31
Support Year
2
Fiscal Year
2009
Total Cost
$63,000
Indirect Cost

  Institution

Name
University of Oklahoma Health Sciences Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
878648294
City
Oklahoma City
State
OK
Country
United States
Zip Code
73117

  Publications

Hughes, Travis; Adler, Adam; Merrill, Joan T et al. (2012) Analysis of autosomal genes reveals gene-sex interactions and higher total genetic risk in men with systemic lupus erythematosus. Ann Rheum Dis 71:694-9
Hughes, Travis; Adler, Adam; Kelly, Jennifer A et al. (2012) Evidence for gene-gene epistatic interactions among susceptibility loci for systemic lupus erythematosus. Arthritis Rheum 64:485-92
Sawalha, Amr H; Wang, Lu; Nadig, Ajay et al. (2012) Sex-specific differences in the relationship between genetic susceptibility, T cell DNA demethylation and lupus flare severity. J Autoimmun 38:J216-22
Sawalha, Amr H; Hughes, Travis; Nadig, Ajay et al. (2011) A putative functional variant within the UBAC2 gene is associated with increased risk of Behcet's disease. Arthritis Rheum 63:3607-12
Jeffries, Matlock A; Sawalha, Amr H (2011) Epigenetics in systemic lupus erythematosus: leading the way for specific therapeutic agents. Int J Clin Rheumtol 6:423-439
Sánchez, Elena; Comeau, Mary E; Freedman, Barry I et al. (2011) Identification of novel genetic susceptibility loci in African American lupus patients in a candidate gene association study. Arthritis Rheum 63:3493-501
Htoon, Jasmine; Nadig, Ajay; Hughes, Travis et al. (2011) IL18 polymorphism is associated with Behçet's disease but not lupus in patients from Turkey. J Rheumatol 38:962-3
Webb, Ryan; Kelly, Jennifer A; Somers, Emily C et al. (2011) Early disease onset is predicted by a higher genetic risk for lupus and is associated with a more severe phenotype in lupus patients. Ann Rheum Dis 70:151-6
Sanchez, Elena; Nadig, Ajay; Richardson, Bruce C et al. (2011) Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus. Ann Rheum Dis 70:1752-7
Hughes, Travis; Kim-Howard, Xana; Kelly, Jennifer A et al. (2011) Fine-mapping and transethnic genotyping establish IL2/IL21 genetic association with lupus and localize this genetic effect to IL21. Arthritis Rheum 63:1689-97

Showing the most recent 10 out of 20 publications