Department of Medical Genetics and Medical Research, China Medical University Hospital, No,2 Yuh-Der Road, 404 Taichung City, Taiwan.
BMC Ophthalmol. 2014 Feb 11;14:15. doi: 10.1186/1471-2415-14-15.
Graves' disease (GD) and Graves' ophthalmopathy (GO) are autoimmune disorders, which might be influenced by genetic factors. Copy number variation (CNV) is an important source of genomic diversity in humans, and influences disease susceptibility. This study investigated the association between CNV in the TSHR and TLR7 genes and the development of GD and GO in a Chinese population in Taiwan.
For this case-control study, sample from 196 healthy controls and 484 GD patients, including 203 patients with GO were studied. CNV was detected by real-time polymerase chain reaction (PCR) using TaqMan™ probes and the relative copy number (CN) was estimated by using the comparative Ct method.
The differences in the distribution of TSHR CNV in healthy controls and GD patients were statistically significant (p value = 0.01). However, the difference in the distribution of TSHR CNV in the control group and the GO group was not statistically significant (p value = 0.06). For TLR7 CNV, the results were not significantly different when we compared the distribution in healthy controls and GD patients and in healthy controls and GO patients (p values for Fisher's exact test were 0.13 and 0.09, respectively). However, a lower than normal CNV for TLR7 (CNV < 2 for female and CNV < 1 for male) was found to have a protective effect against the development of GD (odds ratio (OR) = 0.24; 95% confidence interval (CI), 0.07-0.75) after adjusting for age and gender.
These results suggested that TSHR and TLR7 CNV might be associated with susceptibility to GD.
格雷夫斯病（GD）和格雷夫斯眼病（GO）是自身免疫性疾病，可能受遗传因素影响。拷贝数变异（CNV）是人类基因组多样性的重要来源，并且影响疾病易感性。本研究在台湾汉族人群中研究了 TSHR 和 TLR7 基因的 CNV 与 GD 和 GO 发病的关系。
本病例对照研究共检测了 196 例健康对照者和 484 例 GD 患者，包括 203 例 GO 患者的样本。通过 TaqMan™探针实时 PCR 检测 CNV，并用比较 Ct 法估计相对拷贝数（CN）。
TSHR CNV 在健康对照者和 GD 患者中的分布差异有统计学意义（p 值=0.01）。然而，在健康对照组和 GO 组之间，TSHR CNV 的分布差异无统计学意义（p 值=0.06）。对于 TLR7 CNV，在健康对照组和 GD 患者以及健康对照组和 GO 患者之间的分布比较中，结果均无统计学差异（Fisher 确切检验的 p 值分别为 0.13 和 0.09）。然而，发现 TLR7 低于正常的 CNV（女性的 CNV<2，男性的 CNV<1）对 GD 的发生有保护作用（调整年龄和性别后，优势比（OR）=0.24；95%置信区间（CI），0.07-0.75）。
这些结果表明 TSHR 和 TLR7 CNV 可能与 GD 的易感性有关。
