Molecular Thyroid Research Laboratory, Johannes Gutenberg University Medical Center, Mainz, Germany.
Institute of Legal Medicine, Johannes Gutenberg University Medical Center, Mainz, Germany.
J Clin Endocrinol Metab. 2018 May 1;103(5):1977-1984. doi: 10.1210/jc.2017-02577.
Single nucleotide polymorphisms (SNPs) of various genes increase susceptibility to monoglandular autoimmunity. Data on autoimmune polyglandular syndromes (APSs) are scarce.
Evaluate potential associations of eight SNPs with APSs.
Academic referral endocrine clinic.
A total of 543 patients with APS and monoglandular autoimmunity and controls.
The SNP protein tyrosine phosphatase nonreceptor type 22 (PTPN22) rs2476601 (+1858); cytotoxic T-lymphocyte‒associated antigen 4 (CTLA-4) rs3087243 (CT60) and rs231775 (AG49); vitamin D receptor (VDR) rs1544410 (Bsm I), rs7975232 (Apa I), rs731236 (Taq I); tumor necrosis factor α rs1800630 (-863); and interleukin-2 receptor alpha rs10795791 were tested by single-base extension in all subjects.
The PTPN22 +1858 allele and genotype distribution were markedly different between APS, type 1 diabetes [T1D; odds ratio (OR): 2.67; 95% confidence interval (CI): 1.52 to 4.68; P = 0.001], Graves disease (GD; OR: 1.94; 95% CI: 1.16 to 3.25; P = 0.011), and controls (OR: 3.31, 95% CI: 1.82 to 6.02; P < 0.001). T-allele carriers' risk for APS was increased (OR: 3.76; 95% CI: 1.97 to 7.14; P < 0.001). T-allele frequency was higher among APS than controls (OR: 3.25; 95% CI: 1.82 to 5.82; P < 0.001), T1D (OR: 2.54; 95% CI: 1.48 to 4.36; P = 0.001), or GD (OR: 1.89; 95% CI: 1.15 to 3.11; P = 0.012). The SNP CTLA-4 CT60 G-allele carriers were more frequent in APS (85%) than controls (78%) (OR: 1.55; 95% CI: 0.81 to 2.99). Combined analysis of CTLA-4 AG49 and CT60 revealed OR 4.89; 95% CI: 1.86 to13.59; P = 0.00018 of the genotype combination AG/GG for APS vs controls. VDR polymorphisms Bsm I, Apa I, and Taq I did not, but the haplotypes differed between APS and controls (P = 0.0011).
PTPN22 and CTLA-4 polymorphisms are associated with APS and differentiate between polyglandular and monoglandular autoimmunity.
各种基因的单核苷酸多态性（SNPs）增加了单腺体自身免疫的易感性。自身免疫多腺体综合征（APS）的数据很少。
评估八个 SNPs 与 APS 的潜在关联。
学术转诊内分泌诊所。
共 543 例 APS 和单腺体自身免疫患者及对照者。
蛋白酪氨酸磷酸酶非受体型 22（PTPN22）rs2476601（+1858）；细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）rs3087243（CT60）和 rs231775（AG49）；维生素 D 受体（VDR）rs1544410（Bsm I）、rs7975232（Apa I）、rs731236（Taq I）；肿瘤坏死因子-α rs1800630（-863）；白细胞介素-2 受体 α rs10795791 通过单碱基延伸在所有受试者中进行测试。
APS、1 型糖尿病[T1D；优势比（OR）：2.67；95%置信区间（CI）：1.52 至 4.68；P = 0.001]、格雷夫斯病（GD；OR：1.94；95%CI：1.16 至 3.25；P = 0.011）和对照组（OR：3.31，95%CI：1.82 至 6.02；P < 0.001）之间，PTPN22+1858 等位基因和基因型分布明显不同。T 等位基因携带者发生 APS 的风险增加（OR：3.76；95%CI：1.97 至 7.14；P < 0.001）。APS 患者 T 等位基因频率高于对照组（OR：3.25；95%CI：1.82 至 5.82；P < 0.001）、T1D（OR：2.54；95%CI：1.48 至 4.36；P = 0.001）或 GD（OR：1.89；95%CI：1.15 至 3.11；P = 0.012）。CTLA-4 CT60 G-等位基因携带者在 APS 中更为常见（85%），而对照组中更为常见（78%）（OR：1.55；95%CI：0.81 至 2.99）。对 CTLA-4 AG49 和 CT60 进行联合分析显示，APS 与对照组相比，AG/GG 基因型组合的 OR 为 4.89；95%CI：1.86 至 13.59；P = 0.00018。VDR 多态性 Bsm I、Apa I 和 Taq I 不相关，但 APS 与对照组之间存在不同的单倍型（P = 0.0011）。
PTPN22 和 CTLA-4 多态性与 APS 相关，并区分多腺体和单腺体自身免疫。
