The Mannose-binding lectin gene polymorphisms and systemic lupus erythematosus - Two case-control studies and a meta-analysis
The Mannose-binding lectin gene polymorphisms and systemic lupus erythematosus - Two case-control studies and a meta-analysis
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DOI：
10.1002/art.21484
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发表时间：
2005-12-01
影响因子：
--
通讯作者：
Sestak, AL
中科院分区：
文献类型：
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作者：
Lee, YH;Witte, T;Sestak, AL
客观的。甘露糖结合凝集素 (MBL) 增强调理作用并激活补体。 MBL 功能失调的等位基因与 MBL 血浆浓度低和系统性红斑狼疮 (SLE) 风险增加有关，但基因分型研究显示结果不一致。我们对 2 个白人队列中的 MBL 多态性进行了病例对照研究，并纳入了所有已发表的 SLE 中 MBL 基因分型结果的荟萃分析，以探讨 MBL 功能变异是否与 SLE 相关。方法。对 96 名欧洲裔美国 SLE 患者和 96 名年龄、种族和性别匹配的对照患者的 7 个单核苷酸多态性的 MBL 基因型进行了测序。对 285 名德国 SLE 患者和 200 名种族匹配对照者的 MBL 密码子 52、54 和 57 进行了基因分型。统计所有已知变异的等位基因频率以进行荟萃分析。结果。尽管在所评估的两个患者队列中都存在与 MBL 多态性相关的趋势，但它们本身均不与 SLE 显着相关。荟萃分析中纳入了来自 15 项研究的 17 项比较。 Egger 回归检验排除了发表偏倚（P = 0.14）。 MBL 密码子 54 变体 B 的总体优势比为 1.406（95% 置信区间 1.221-1.608；P < 0.001）。按种族分层显示，在非洲、亚洲和白种人队列中，MBL 密码子 54B 变异与 SLE 相关的比值比显着增加。结论。对所有 MBL 多态性和 SLE 现有研究的荟萃分析表明，MBL 变异等位基因（例如 MBL 外显子 1 密码子 54 B、启动子 -550 L 和启动子 -221 X）是 SLE 危险因素。这种关联性很强，并且在纳入我们的两个队列的数据后仍然存在，其中该关联性未能达到显着性。
Objective. Mannose-binding lectin (MBL) enhances opsonization and activates complement. Dysfunctional alleles of MBL have been associated with low plasma concentrations of MBL and increased risk of systemic lupus erythematosus (SLE), but genotyping studies have shown inconsistent results. We performed case-control studies of the MBL polymorphisms in 2 Caucasian cohorts and a meta-analysis incorporating all published results of MBL genotyping in SLE to explore whether the MBL functional variants are associated with SLE.Methods. MBL genotypes at 7 single-nucleotide polymorphisms were sequenced in 96 European American patients with SLE and 96 age-, race-, and sex-matched controls. MBL codons 52, 54, and 57 were genotyped in 285 German patients with SLE and 200 race-matched controls. Allele frequencies of all known variants were tallied for meta-analysis.Results. Although there was a trend toward association with MBL polymorphisms in both patient cohorts evaluated, none of them was significantly associated with SLE on its own. Seventeen comparisons from 15 studies were included in the meta-analysis. Publication bias was excluded by Egger's regression test (P = 0.14). The overall odds ratio for MBL codon 54 variant B was 1.406 (95% confidence interval 1.221-1.608; P < 0.001). Stratification by ethnicity showed significantly increased odds ratios for association of the MBL codon 54B variant with SLE in African, Asian, and Caucasian cohorts.Conclusion. Meta-analysis of all available studies on MBL polymorphisms and SLE shows that MBL variant alleles such as MBL exon 1 codon 54 B, promoter -550 L, and promoter -221 X are SLE risk factors. This association is robust and persists after incorporation of data from our 2 cohorts in which the association failed to reach significance.