Evaluation of 19 autoimmune disease-associated loci with rheumatoid arthritis in a Colombian population: evidence for replication and gene-gene interaction.
Evaluation of 19 autoimmune disease-associated loci with rheumatoid arthritis in a Colombian population: evidence for replication and gene-gene interaction.
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DOI：
10.3899/jrheum.110199
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发表时间：
2011-09
期刊：
影响因子：
--
通讯作者：
Nath SK
中科院分区：
文献类型：
--
作者：
Deshmukh HA;Maiti AK;Kim-Howard XR;Rojas-Villarraga A;Guthridge JM;Anaya JM;Nath SK
最近的研究已经确定了与多种自身免疫性疾病相关的几个共同基因，支持存在共享或一般自身免疫基因的假设。然而，这项工作的大部分已经在白色血统的人群中进行。本研究的主要目的是复制19个这样的变体和类风湿性关节炎（RA）之间的基因型-表型相关性，并评估这些基因在一个种族同质的非白人哥伦比亚人口的个体之间的基因-基因相互作用。对353例RA患者和368例对照者的16个基因/位点的19个单核苷酸多态性（SNP）进行了基因分型。对于每个SNP，应用等位基因和基于基因型的关联检验来评估基因型-表型相关性。使用基于排列的检验来验证统计学显著性。基因-基因相互作用通过逻辑回归进行评估。我们复制了与rs 13277113的遗传关联，（p = 0.0009，OR 1.46）和rs 2736340（p = 0.0001，OR 1.63）来自C8 orf 13-BLK（8p23.1，与RA和系统性红斑狼疮相关）和rs763361（p = 0.03）来自哥伦比亚人群中的CD 226（18q22.3，与多发性硬化症和1型糖尿病相关）。rs 13277113、rs 2736340和rs763361的人群归因风险估计分别为27%、34%和16%。我们还检测到MMEL 1（rs3890745）和C80 rf 13-BLK（rs 13277113; p = 0.0002）中SNP之间的基因-基因相互作用的证据。我们的研究结果表明，IL 2/IL 21区域，C8 orf 13-BLK，和CD 226影响RA在中国，和RA共享与其他自身免疫性疾病相关的一些致病机制。
Recent studies have identified several common genes associated with multiple autoimmune diseases that support the hypothesis of the presence of shared or general autoimmunity genes. However, most of this work has been performed in populations of white origin. The main objectives of this study are to replicate the genotype-phenotype correlation between 19 such variants and rheumatoid arthritis (RA), and to evaluate gene-gene interactions between these genes in individuals from an ethnically homogenous nonwhite Colombian population. Nineteen single-nucleotide polymorphisms (SNP) from 16 genes/loci were genotyped in 353 RA cases and 368 controls. For each SNP, allelic and genotype-based association tests were applied to evaluate genotype-phenotype correlation. Permutation-based tests were used to validate the statistical significance. Gene-gene interactions were assessed by logistic regression. We replicated the genetic association with rs13277113 (p = 0.0009, OR 1.46) and rs2736340 (p = 0.0001, OR 1.63) from C8orf13-BLK (8p23.1, associated with RA and systemic lupus erythematosus), and rs763361 (p = 0.03) from CD226 (18q22.3, associated with multiple sclerosis and type 1 diabetes) in the Colombian population. The population-attributable risks were estimated as 27%, 34%, and 16% for rs13277113, rs2736340, and rs763361, respectively. We also detected evidence for gene-gene interaction between SNP in MMEL1 (rs3890745) and C80rf13-BLK (rs13277113; p = 0.0002). Our results demonstrate that the IL2/IL21 region, C8orf13-BLK, and CD226 influence RA in Colombians, and RA shares some of the pathogenic mechanisms associated with other autoimmune diseases.
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