The protein tyrosine phosphatase nonreceptor 22 (PTPN22) is associated with high GAD antibody titer in latent autoimmune diabetes in adults -: Non Insulin Requiring Autoimmune Diabetes (NIRAD) study 3
The protein tyrosine phosphatase nonreceptor 22 (PTPN22) is associated with high GAD antibody titer in latent autoimmune diabetes in adults -: Non Insulin Requiring Autoimmune Diabetes (NIRAD) study 3
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DOI：
10.2337/dc07-1457
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发表时间：
2008-03-01
期刊：
影响因子：
16.2
通讯作者：
Buzzetti, Raffaella
中科院分区：
文献类型：
--
作者：
Petrone, Antonio;Suraci, Concetta;Buzzetti, Raffaella
目的 - 我们之前证明了成人发病的自身免疫性糖尿病患者中存在两种不同的人群：具有高滴度或低滴度的 GAD (GADA) 抗体的人群。 22型蛋白酪氨酸磷酸酶非受体（PTPN22）已被确定为1型糖尿病和其他自身免疫性疾病的新易感基因。本研究的目的是评估基于 GADA 滴度的成人发病型自身免疫性糖尿病的表型异质性是否与 PTPN22 C1858T 多态性相关。 研究设计和方法 - 使用 TaqMan 测定法对 250 名成人发病型自身免疫性糖尿病受试者进行 C1858T 多态性分析，分为两个亚组（低（32 任意））单位）GADA 滴度和 450 名典型 2 型糖尿病受试者（来自 5,330 名成人发病糖尿病受试者的非胰岛素需要自身免疫性糖尿病 [NIRAD] 研究队列）以及 558 名青少年发病 1 型糖尿病受试者和 545 名血糖正常受试者。 结果 - PTPN22 C1858T 的基因型、等位基因和表型分布变体显示高 GADA 滴度的自身免疫性糖尿病和青少年发病的 1 型糖尿病的发生率相似。与低 GADA 滴度个体、2 型糖尿病患者和对照受试者相比，高 GADA 滴度个体的 TT 和 CT 基因型有所增加（所有比较 P < 0.002）。与低 GADA 滴度、2 型糖尿病和对照受试者相比，高 GADA 滴度的 PTPN22 1858T 等位基因和表型频率增加（所有比较 P < 0.001，比值比 2.6）。结论 - 在成人发病的自身免疫性糖尿病中，PTPN22 1858T 变异仅与高 GADA 滴度相关，为临床提供遗传背景的证据通过 GADA 滴度鉴定异质性。
OBJECTIVE - We previously demonstrated the presence of two different populations among individuals With adult-onset autoimmune diabetes: those having either a high titer or a low titer of antibodies to GAD (GADAs). Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) has been identified as a new susceptibility gene for type 1 diabetes and other autoimmune diseases. The aim of the present study was to evaluate whether the phenotypic heterogeneity of adult-onset autoimmune diabetes based on the GADA titer is associated with the PTPN22 C1858T polymorphism.RESEARCH DESIGN AND METHODS - Analysis for the C1858T polymorphism using the TaqMan assay was performed in 250 subjects with adult-onset autoimmune diabetes, divided into two subgroups with low ( 32 arbitrary units) GADA titers and 450 subjects with classic type 2 diabetes (from the Non Insulin Requiring Autoimmune Diabetes [NIRAD] Study cohort of 5,330 subjects with adult-onset diabetes) and in 558 subjects with juvenile-onset type 1 diabetes and 545 normoglycemic subjects.RESULTS - Genotype, allele, and phenotype distributions of the PTPN22 C1858T variant revealed similar frequencies in autoimmune diabetes with high GADA titer and juvenile-onset type 1 diabetes. An increase in TT and CT genotypes was observed in individuals with a high GADA titer compared with a low GADA titer, those with type 2 diabetes, and control subjects (P < 0.002 for all comparisons). The PTPN22 1858T allele and phenotype frequencies were increased in high GADA titer compared with a low GADA titer, type 2 diabetic, and control subjects (P < 0.001 for all comparisons, odds ratio 2.6).CONCLUSIONS - In adult-onset autoimmune diabetes, the PTPN22 1858T variant is associated only with a high GADA titer, providing evidence of a genetic background to clinical heterogeneity identified by GADA titer.