Dultz Georg, Matheis Nina, Dittmar Manuela, Röhrig Bernd, Bender Klaus, Kahaly George J
Department of Medicine I, Gutenberg University, Mainz, Germany.
Thyroid. 2009 Feb;19(2):143-8. doi: 10.1089/thy.2008.0301.
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.
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.
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).
The PTPN22 gene is a joint susceptibility locus for AITD (especially HT) and T1D.
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。
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。
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）。
PTPN22基因是AITD（尤其是HT）和T1D的联合易感基因座。
