Meta-analysis of TNF-α promoter - 308 A/G polymorphism and SLE susceptibility

Young H. Lee, John B. Harley, Swapan K. Nath

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    165 Citations (Scopus)


    Alleles of tumor necrosis factor-Alleles of tumor necrosis factor-α (TNF-α) gene have been inconsistently associated with systemic lupus erythematosus (SLE), particularly the 308-A/G functional promoter polymorphism. To generate large-scale evidence on whether 308-A/G promoter polymorphism is associated with SLE susceptibility we have conducted a meta-analysis. We have identified 21 studies of this polymorphism and SLE using MEDLINE search. Meta-analysis was performed for genotypes A/A (recessive effect), A/A + A/G (dominant effect), and A allele in fixed or random effects models. All control samples were in Hardy-Weinberg proportion. The overall odds ratio (OR) of the A/A genotype was 3.2 (95% CI = 2.0-5.3, P<0.001). Stratification by ethnicity indicated that the A/A genotype was associated with SLE in European-derived population (OR = 4.0, CI = 2.5-6.4, P<0.001). No association was detected in Asian-derived population (OR, 1.3, CI = 0.3-6.3, P = 0.76). The overall OR for the risk genotypes (A/A and A/G) was 2.0 (CI = 1.3-3.1,P<0.001). Similar results were found between the risk allele A and SLE where a significant association was found in European population (OR = 2.1, CI = 1.6-2.7, Po0.001), but not in Asian (OR = 1.4, CI = 0.8-2.3, P = 0.2) or African (OR = 1.2, CI = 0.6-2.5, P = 0.59) populations. In summary, this meta-analysis demonstrates that the TNF-α promoter -308 A/G polymorphism may confer susceptibility to SLE, especially in European-derived population.

    Original languageEnglish
    Pages (from-to)364-371
    Number of pages8
    JournalEuropean Journal of Human Genetics
    Issue number3
    Publication statusPublished - 2006 Mar

    Bibliographical note

    Funding Information:
    This work was supported by the National Institutes of Health (AR048928, AI063622, RR020143, AR049084, AI24717, AR42460, AR048940, AI053747, AR12253, DE15223, RR01577, RR14467) and the US Department of Veterans Affairs.


    • Meta-analysis
    • SLE
    • TNF-α

    ASJC Scopus subject areas

    • Genetics
    • Genetics(clinical)


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