Genetic variations in ZFP36 and their possible relationship to autoimmune diseases
Genetic variations in ZFP36 and their possible relationship to autoimmune diseases
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DOI：
10.1016/j.jaut.2006.01.004
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发表时间：
2006-05-01
影响因子：
12.8
通讯作者：
Blackshear, Perry J.
中科院分区：
文献类型：
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作者：
Carrick, Danielle Mercatante;Chulada, Patricia;Blackshear, Perry J.
ZFP36基因编码TTP，TTP是肿瘤坏死因子α的调节因子。在小鼠中，TTP缺乏会导致全身性自身免疫性炎症综合征和严重的关节炎。我们假设ZFP36的基因变异与人类自身免疫性疾病有关。这项研究的主要目的是在自身免疫性疾病患者和对照中鉴定人类ZFP36基因变异，确定它们在普通临床人群中的频率，并构建单倍型。我们对316名自身免疫性疾病患者的ZFP36进行了重新测序，确定了28个多态，并确定了环境多态登记的484名参与者中所有已知ZFP36多态的频率。环境多态登记是由NIEHS进行的区域登记。基于序列验证的ZFP36基因，构建了34个单倍型。作为第二个目标，我们检查了自身免疫性疾病的病例和对照，以寻找潜在的ZFP36基因关联。在非裔美国人中，一个新的多态ZFP36*8与类风湿性关节炎(RA)显著相关(RR=1.23，95%CI：1.11-1.36)。这里提供的数据表明ZFP36和RA之间存在初步的关联。这一发现，以及这里发现的ZFP36多态和单倍型，应该构成未来自身免疫性疾病关联研究的基础。爱思唯尔有限公司出版。
The ZFP36 gene codes for TTP, a regulator of TNF alpha. In mice, TTP deficiency results in a systemic autoimmune inflammatory syndrome with severe arthritis. We hypothesized that genetic variations in ZFP36 are associated with autoimmune disease in humans. The primary objective of this study was to identify human ZFP36 genetic variants in autoimmune disease cases and controls, determine their frequencies in a general clinic population, and construct haplotypes. We resequenced ZFP36 in 316 individuals with autoimmune diseases and identified 28 polymorphisms and determined the frequency of all the known ZFP36 polymorphisms in 484 participants of the Environmental Polymorphism Registry, a regional registry being conducted by the NIEHS. Based on the sequence-verified ZFP36 genotypes, 34 haplotypes were constructed. As a secondary objective, we examined autoimmune disease cases and controls for potential ZFP36 genetic associations. One novel polymorphism, ZFP36*8, a C to T transition in the protein coding domain, was significantly associated with rheumatoid arthritis (RA) in African-Americans (RR = 1.23, 95% CI: 1.11-1.36). The data presented here suggest a tentative association between ZFP36 and RA. This finding, as well as the ZFP36 polymorphisms and haplotypes identified here, should form the basis for future association studies in autoimmune diseases. Published by Elsevier Ltd.