Meta-analysis of TNF-α promoter-308 A/G polymorphism and SLE susceptibility
Meta-analysis of TNF-α promoter-308 A/G polymorphism and SLE susceptibility
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DOI：
10.1038/sj.ejhg.5201566
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发表时间：
2006-03-01
影响因子：
5.2
通讯作者：
Nath, SK
中科院分区：
文献类型：
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作者：
Lee, YH;Harley, JB;Nath, SK
肿瘤坏死因子-α(TNF-α)基因等位基因与系统性红斑狼疮(SLE)的相关性不一致，尤其是308-A/G功能启动子多态性。为了证明308-A/G启动子多态性是否与SLE易感性相关的大规模证据，我们进行了一项荟萃分析。我们已经用MEDLINE搜索确定了21个关于这种多态性和系统性红斑狼疮的研究。在固定或随机效应模型中对A/A(隐性效应)、A/A+A/G(显性效应)和A等位基因进行Meta分析。所有对照样品均符合Hardy-Weinberg比例。A/A基因型的OR值为3.2(95%CI=2.0~5.3，P<；0.001)。按种族分层显示，在欧洲人群中，A/A基因型与系统性红斑狼疮相关(OR4.0，CI=2.56.4，P<；0.001)。在亚洲人群中未发现关联(OR，1.3，CI=0.3-6.3，P=0.76)。危险基因(A/A和A/G)的总体OR值为2.0(CI=1.3~3.1，P<；0.001)。在欧洲人群(OR=2.1，CI=1.6~2.7，P<；0.001)，而在亚洲人群(OR=1.4，CI=0.8~2.3，P=0.2)和非洲人群(OR=1.2，CI=0.6~2.5，P=0.5 9)中无显著关联。综上所述，这一荟萃分析表明，肿瘤坏死因子-α启动子-308A/G多态可能增加SLE的易感性，特别是在欧洲人群中。
Alleles of tumor necrosis factor-alpha (TNF-alpha) 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, P < 0.001), 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-alpha promoter -308 A/G polymorphism may confer susceptibility to SLE, especially in European-derived population.