The ITGAV rs3738919-C allele is associated with rheumatoid arthritis in the European Caucasian population: a family-based study.
The ITGAV rs3738919-C allele is associated with rheumatoid arthritis in the European Caucasian population: a family-based study.
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DOI：
10.1186/ar2221
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发表时间：
2007
影响因子：
4.9
通讯作者：
Cornelis, Francois
中科院分区：
文献类型：
--
作者：
Jacq, Laurent;Garnier, Sophie;Dieude, Philippe;Michou, Laetitia;Pierlot, Celine;Migliorini, Paola;Balsa, Alejandro;Westhovens, Rene;Barrera, Pilar;Alves, Helena;Vaz, Carlos;Fernandes, Manuela;Pascual-Salcedo, Dora;Bombardieri, Stefano;Dequeker, Jan;Radstake, Timothy R;Van Riel, Piet;van de Putte, Leo;Lopes-Vaz, Antonio;Glikmans, Elodie;Barbet, Sandra;Lasbleiz, Sandra;Lemaire, Isabelle;Quillet, Patrick;Hilliquin, Pascal;Teixeira, Vitor Hugo;Petit-Teixeira, Elisabeth;Mbarek, Hamdi;Prum, Bernard;Bardin, Thomas;Cornelis, Francois
整合素αvβ3的αv亚基由ITGAV基因编码，在血管生成中起关键作用。类风湿性关节炎（RA）与血管增生有关，ITGAV基因位于2 q31，是RA的易感基因之一。我们的目的是在一项来自欧洲高加索人群的以家族为基础的研究中检测ITGAV基因与RA的关联和连锁。两个单核苷酸多态性的基因分型PCR-限制性片段长度多态性在100个法国白人RA三人家庭（RA患者和父母），100个其他法国家庭和265个欧洲家庭可供复制。使用等位基因频率（受影响的家庭为基础的控制），传播不平衡检验，和基因型相对风险的比较进行关联和连锁的遗传分析。我们在第一个样本中观察到rs3738919的C等位基因与RA显著相关（受影响的以家庭为基础的对照组，RA指数病例为66.5%，对照组为56.7%; P = 0.04）。第二个样本显示出相同的趋势，第三个样本再次显示出显著的RA相关性。当所有数据集合并时，证实了相关性（受累家族对照组，RA指数病例为64.6%，对照组为58.1%; P = 0.005）。rs3738919-C等位基因也与RA连锁（传递不平衡检验，56.5%对50%的传递; P = 0.009），含C等位基因的基因型在RA指数病例中比对照组更常见（RA指数病例372例与对照组339例; P = 0.002，比值比= 1.94，95%置信区间= 1.3-2.9）。ITGAV基因的rs3738919-C等位基因与欧洲高加索人群中的RA相关，表明ITGAV是一个新的轻微RA易感基因。
The integrin αvβ3, whose αv subunit is encoded by the ITGAV gene, plays a key role in angiogenesis. Hyperangiogenesis is involved in rheumatoid arthritis (RA) and the ITGAV gene is located in 2q31, one of the suggested RA susceptibility loci. Our aim was to test the ITGAV gene for association and linkage to RA in a family-based study from the European Caucasian population. Two single nucleotide polymorphisms were genotyped by PCR-restriction fragment length polymorphism in 100 French Caucasian RA trio families (one RA patient and both parents), 100 other French families and 265 European families available for replication. The genetic analyses for association and linkage were performed using the comparison of allelic frequencies (affected family-based controls), the transmission disequilibrium test, and the genotype relative risk. We observed a significant RA association for the C allele of rs3738919 in the first sample (affected family-based controls, RA index cases 66.5% versus controls 56.7%; P = 0.04). The second sample showed the same trend, and the third sample again showed a significant RA association. When all sets were combined, the association was confirmed (affected family-based controls, RA index cases 64.6% versus controls 58.1%; P = 0.005). The rs3738919-C allele was also linked to RA (transmission disequilibrium test, 56.5% versus50% of transmission; P = 0.009) and the C-allele-containing genotype was more frequent in RA index cases than in controls (RA index cases 372 versus controls 339; P = 0.002, odds ratio = 1.94, 95% confidence interval = 1.3–2.9). The rs3738919-C allele of the ITGAV gene is associated with RA in the European Caucasian population, suggesting ITGAV as a new minor RA susceptibility gene.