| Title | Genetic polymorphisms in tumor necrosis factor (TNF)-alpha and TNF-beta in a population-based study of systemic lupus erythematosus: associations and interaction with the interleukin-1alpha-889 C/T polymorphism. | | Author(s) | Parks CG, Pandey JP, Dooley MA, Treadwell EL, St Clair EW, Gilkeson GS, Feghali-Bostwick CA, Feghali-Botswick CL, Cooper GS | | Institution | National Institute of Environmental Health Sciences, Durham, NC, USA. parks@niehs.nih.gov | | Source | Hum Immunol 2004 Jun; 65(6):622-31. | | MeSH | Adult
African Americans
Alleles
Epistasis, Genetic
European Continental Ancestry Group
Female
Gene Frequency
Genetic Predisposition to Disease
Genotype
Humans
Interleukin-1
Lupus Erythematosus, Systemic
Lymphotoxin
Male
Middle Aged
Polymorphism, Genetic
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Southeastern United States
Tumor Necrosis Factor-alpha
| | Abstract | Tumor necrosis factor (TNF) is involved in the pathogenesis of systemic lupus erythematosus (SLE), but the role of TNF polymorphisms in SLE susceptibility remains unclear. Previous studies in different populations report an inconsistent association of the TNF-alpha -308A allele with SLE, sometimes depending on the presence of HLA-DR3. We examined the association of polymorphisms in TNF-alpha (-308G/A, -238G/A) and TNFbeta (+252A/G) in a population-based study of SLE in the southeastern United States and considered TNF-SLE associations with respect to HLA-DR3 and DR2 and the interleukin (IL)-1alpha -889C/T polymorphism, previously linked to SLE in this population. Genotypes were analyzed for 230 recently diagnosed SLE patients who met American College of Rheumatology classification criteria and 276 age- and sex-matched controls, randomly selected from driver's license registries. Carriage of the TNF-alpha -308A allele was significantly associated with SLE in Caucasians (OR = 2.3; 95% CI 1.4, 3.9), but not African Americans. Analyses stratified by IL-1alpha -889 genotypes (C/C vs C/T or T/T) revealed independent associations of SLE with TNF-alpha -308A or HLA-DR2 and DR3. This reflected a significant interaction of TNF and IL-1 genotypes in Caucasians, and yielded a strong association (OR = 8.0, p < 0.00001) for the combined "HLA-DR3, TNF-alpha -308A, IL-1alpha -889C/C" genotype. These findings provide evidence of cytokine gene epistasis in SLE susceptibility. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 15219382 |
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