Tag SNP screening of the PDCD1 gene for association with Graves' disease
Tag SNP screening of the PDCD1 gene for association with Graves' disease
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DOI：
10.1111/j.1365-2265.2007.02848.x
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发表时间：
2007-07-01
影响因子：
3.2
通讯作者：
Simmonds, M. J.
中科院分区：
文献类型：
--
作者：
Newby, P. R.;Roberts-Davies, E. L.;Simmonds, M. J.
目的2q37.3染色体上的程序性细胞死亡1基因（PDCD1）编码PD-1，该基因参与向活化的T细胞提供负信号。大型病例对照研究显示PDCD1与几种自身免疫性疾病有关，但迄今为止，尚无针对Graves病（GD）的此类研究。我们研究的目的是在一个特征良好的英国高加索GD数据集中研究代表PDCD1大多数常见变异的8个标签snp。设计8个多态性的病例对照关联研究。2671例Graves病患者和864例对照者。测量与疾病相关的测试。结果本研究中+4163、+5049、+5318、+5640、+5678和+7078基因型的snp均未发现与疾病相关。+2375 SNP （P = 0.021, OR = 1.14 [95% CI = 1.01-1.29]）与GD之间存在相关性，+6799 SNP基因型具有较小的保护作用（P = 0.028, OR = 0.77 [95% CI = 0.58-1.03]）。本研究首次表明，PDCD1内的小影响可能有助于GD的发展，支持了目前未知的GD遗传贡献可能是由于ORs 1.2的几个小遗传效应的假设。现在需要复制这一结果来证实我们的发现，并证明在该基因区域更详细的精细定位主要病因变异。
Objective The Programmed Cell Death 1 gene (PDCD1) on chromosome 2q37.3 encodes PD-1 which is involved in providing a negative signal to activated T cells. Large case-control studies have shown association of PDCD1 with several autoimmune diseases although, to date, no such studies have been performed for Graves' disease (GD). The objective of our study was to investigate eight tag SNPs representing the majority of common variation in PDCD1 within a well-characterized large UK Caucasian GD dataset.Design A case control association study of eight polymorphisms.Patients 2671 Graves' disease patients and 864 controls.Measurements Tests for association with disease.Results No association with disease was seen for any of the +4163, +5049, +5318, +5640, +5678 and +7078 SNPs genotyped in this study. Association was detected between the +2375 SNP (P = 0.021, OR = 1.14 [95% CI = 1.01-1.29]) and GD and a small protective effect was seen with the +6799 SNP genotypes (P = 0.028, OR = 0.77 [95% CI = 0.58-1.03]).Conclusion This study has, for the first time, shown that small effects within PDCD1 may contribute towards the development of GD, supporting the hypothesis that much of the currently unknown genetic contribution to GD could be due to several small genetic effects with ORs 1.2. Replication of this result is now needed to confirm our findings and justify more detailed fine mapping of a primary aetiological variant in this gene region.