蛋白酪氨酸磷酸酶非受体型22 C1858T多态性是免疫性甲状腺炎和自身免疫性糖尿病的共同易感基因座。

The protein tyrosine phosphatase non-receptor type 22 C1858T polymorphism is a joint susceptibility locus for immunthyroiditis and autoimmune diabetes.

作者信息

Dultz Georg, Matheis Nina, Dittmar Manuela, Röhrig Bernd, Bender Klaus, Kahaly George J

机构信息

Department of Medicine I, Gutenberg University, Mainz, Germany.

出版信息

Thyroid. 2009 Feb;19(2):143-8. doi: 10.1089/thy.2008.0301.

DOI:10.1089/thy.2008.0301

PMID:19090780

Abstract

BACKGROUND

The lymphoid tyrosine phosphatase (LYP) encoded by the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene is a strong inhibitor of T cells. The single nucleotide polymorphism (SNP) C1858T within the PTPN22 gene was recently associated with autoimmune thyroid disease (AITD) and type I diabetes (T1D). The purpose of this study was to examine the joint association of this polymorphism with the co-occurrence of AITD and T1D.

METHODS

In this association study, 310 white subjects were genotyped for the C1858T polymorphism. The study population included 70 patients with both AITD and T1D (AITD+T1D), 70 patients with AITD only, 70 patients with T1D only, and 100 healthy controls. Patients with both AITD and T1D, and controls were also typed for HLA-DRB1. PTPN22 C1858T genotyping was performed by minisequencing. For HLA-DRB1 typing, polymerase chain reaction (PCR) sequence-specific oligonucleotide probes were used.

RESULTS

The PTPN22 1858 minor T-allele frequency was strongly increased in patients with AITD+T1D (23.6%) compared with controls (8.0%, pc<0.001), with patients with AITD only (8.6%, pc=0.006), or with T1D only (10.7%, pc=0.028). T-allele carriers were also more frequently present in the group with AITD+T1D versus controls (41.4% vs. 14.0%, OR=4.35, 95% CI=2.08-9.09), AITD (17.1%, OR=3.42, 95% CI=1.56-7.48), and T1D (21.4%, OR=2.59, 95% CI=1.23-5.45). Especially in subjects with Hashimoto's thyroiditis (HT)+T1D, T-allele carriers were mostly frequent (50% vs. 14%, OR=6.14, 95% CI=2.62-14.38, pc<0.001). Considering all included patients with AITD, T-allele carriers were 29.3% vs. 14.0% in controls (p=0.008, OR=2.54, 95% CI=1.30-4.98). Patients carrying the PTPN22 1858 T allele had a twofold increased frequency of the HLA-DRB1*03 allele (64.7% vs. 37.3%, pc=0.034).

CONCLUSION

The PTPN22 gene is a joint susceptibility locus for AITD (especially HT) and T1D.

摘要

背景

由蛋白酪氨酸磷酸酶非受体22（PTPN22）基因编码的淋巴细胞酪氨酸磷酸酶（LYP）是T细胞的一种强抑制剂。PTPN22基因内的单核苷酸多态性（SNP）C1858T最近与自身免疫性甲状腺疾病（AITD）和I型糖尿病（T1D）相关。本研究的目的是检测这种多态性与AITD和T1D共病的联合关联。

方法

在这项关联研究中，对310名白人受试者进行了C1858T多态性基因分型。研究人群包括70例同时患有AITD和T1D的患者（AITD+T1D）、70例仅患有AITD的患者、70例仅患有T1D的患者以及100名健康对照。对同时患有AITD和T1D的患者及对照也进行了HLA-DRB1分型。通过微测序进行PTPN22 C1858T基因分型。对于HLA-DRB1分型，使用聚合酶链反应（PCR）序列特异性寡核苷酸探针。

结果

与对照（8.0%，pc<0.001）、仅患有AITD的患者（8.6%，pc=0.006）或仅患有T1D的患者（10.7%，pc=0.028）相比，AITD+T1D患者中PTPN22 1858次要T等位基因频率显著升高。与对照（41.4%对14.0%，OR=4.35，95%CI=2.08-9.09）、AITD（17.1%，OR=3.42，95%CI=1.56-7.48）和T1D（21.4%，OR=2.59，95%CI=1.23-5.45）相比，AITD+T1D组中T等位基因携带者也更常见。特别是在桥本甲状腺炎（HT）+T1D患者中，T等位基因携带者最为常见（50%对14%，OR=6.14，95%CI=2.62-14.38，pc<0.001）。考虑所有纳入的AITD患者，对照中T等位基因携带者为29.3%，而患者为14.0%（p=0.008，OR=2.54，95%CI=1.30-4.98）。携带PTPN22 1858 T等位基因的患者HLA-DRB1*03等位基因频率增加两倍（64.7%对37.3%，pc=0.034）。