Epistatic interaction between BANK1 and BLK in rheumatoid arthritis: results from a large trans-ethnic meta-analysis.
Epistatic interaction between BANK1 and BLK in rheumatoid arthritis: results from a large trans-ethnic meta-analysis.
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DOI：
10.1371/journal.pone.0061044
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Dieudé P
中科院分区：
文献类型：
--
作者：
Génin E;Coustet B;Allanore Y;Ito I;Teruel M;Constantin A;Schaeverbeke T;Ruyssen-Witrand A;Tohma S;Cantagrel A;Vittecoq O;Barnetche T;Le Loët X;Fardellone P;Furukawa H;Meyer O;Fernández-Gutiérrez B;Balsa A;González-Gay MA;Chiocchia G;Tsuchiya N;Martin J;Dieudé P
BANK 1和BLK属于多效性自身免疫基因，最近在系统性红斑狼疮中检测到BANK 1和BLK之间的上位性。虽然BLK已被反复鉴定为类风湿性关节炎（RA）的危险因素，但关于BANK 1对RA易感性的贡献的报道存在冲突。为了确定BANK 1对RA遗传易感性的真实的影响，我们进行了一项大型荟萃分析，包括我们的原始数据，并测试了BANK 1和BLK在RA易感性中的上位相互作用。我们调查了1,915名RA患者和1,915名种族匹配的健康对照的数据，这些患者的基因分型为BANK 1 rs 10516487和rs3733197以及BLK rs 13277113。通过Logistic回归分析每个SNP与RA的关联。然后使用具有相互作用项的多变量分析来测试2个基因中的SNP之间的上位相互作用。在基因分型样本中，没有一个单独检测的SNP与RA显著相关。然而，我们检测到BANK 1 rs3733197和BLK rs 13277113之间的上位相互作用（P相互作用= 0.037）。 在携带BLK rs 13277113 GG基因型的个体中，BANK 1 rs3733197 G等位基因的存在增加了RA的风险（比值比1.21 [95%置信区间1.04-1.41]，P = 0.015）。 将我们的结果与所有其他研究的结果结合在一起，进行了一项大型跨种族荟萃分析，结果显示BANK 1 rs3733197 G等位基因与RA相关（1.11 [1.02-1.21]，P = 0.012）。 本研究证实BANK 1是RA的易感基因，并首次为BANK 1和BLK在RA中的上位性提供了证据。我们的研究结果说明了多效性上位相互作用的概念，表明BANK 1和BLK可能在RA发病机制中发挥作用。
BANK1 and BLK belong to the pleiotropic autoimmune genes; recently, epistasis between BANK1 and BLK was detected in systemic lupus erythematosus. Although BLK has been reproducibly identified as a risk factor in rheumatoid arthritis (RA), reports are conflicting about the contribution of BANK1 to RA susceptibility. To ascertain the real impact of BANK1 on RA genetic susceptibility, we performed a large meta-analysis including our original data and tested for an epistatic interaction between BANK1 and BLK in RA susceptibility. We investigated data for 1,915 RA patients and 1,915 ethnically matched healthy controls genotyped for BANK1 rs10516487 and rs3733197 and BLK rs13277113. The association of each SNP and RA was tested by logistic regression. Multivariate analysis was then used with an interaction term to test for an epistatic interaction between the SNPs in the 2 genes. None of the SNPs tested individually was significantly associated with RA in the genotyped samples. However, we detected an epistatic interaction between BANK1 rs3733197 and BLK rs13277113 (Pinteraction = 0.037). In individuals carrying the BLK rs13277113 GG genotype, presence of the BANK1 rs3733197 G allele increased the risk of RA (odds ratio 1.21 [95% confidence interval 1.04–1.41], P = 0.015. Combining our results with those of all other studies in a large trans-ethnic meta-analysis revealed an association of the BANK1 rs3733197 G allele and RA (1.11 [1.02–1.21], P = 0.012). This study confirms BANK1 as an RA susceptibility gene and for the first time provides evidence for epistasis between BANK1 and BLK in RA. Our results illustrate the concept of pleiotropic epistatic interaction, suggesting that BANK1 and BLK might play a role in RA pathogenesis.
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期刊：
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影响因子：
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