PTPN22 R620W functional variant in type 1 diabetes and autoimmunity related traits
PTPN22 R620W functional variant in type 1 diabetes and autoimmunity related traits
复制标题
DOI：
10.2337/db06-0942
复制
发表时间：
2007-02-01
期刊：
影响因子：
7.7
通讯作者：
Julier, Cecile
中科院分区：
文献类型：
--
作者：
Chelala, Claude;Duchatelet, Sabine;Julier, Cecile
PTPN22基因编码淋巴细胞特异性蛋白酪氨酸磷酸酶，是t细胞激活和发育的负调节因子，与几种自身免疫性疾病的易感性相关，包括1型糖尿病。基于联合病例对照和基于家族的关联研究，我们重复了PTPN22 C1858T （R620W）功能变异与I型糖尿病的关联，该关联与胰岛素基因和HLA-DR的易感性状态无关（与其他基因相比，DR3/4）。185ST等位基因导致的风险在有其他自身免疫性疾病家族史的患者中增加，进一步支持该变异在自身免疫中的一般作用。此外，我们发现了1858T等位基因与GAD自身抗体（GADA）存在关联的证据，这种关联仅限于病程较长的患者（10年，P < 0.001）。这可能有助于定义长期持续GADA患者的亚组。1858T等位基因对GAD阳性的影响是加性的，我们的荟萃分析也支持该变异对I型糖尿病的加性而非显性作用，类似于之前对类风湿关节炎和系统性红斑狼疮的报道。
The PTPN22 gene, encoding the lymphoid-specific protein tyrosine phosphatase, a negative regulator in the T-cell activation and development, has been associated with the susceptibility to several autoimmune diseases, including type 1 diabetes. Based on combined case-control and family-based association studies, we replicated the finding of an association of the PTPN22 C1858T (R620W) functional variant with type I diabetes, which was independent from the susceptibility status at the insulin gene and at HLA-DR (DR3/4 compared with others). The risk contributed by the 185ST allele was increased in patients with a family history of other autoimmune diseases, further supporting a general role for this variant on autoimmunity. In addition, we found evidence for an association of 1858T allele with the presence of GAD autoantibodies (GADA), which was restricted to patients with long disease duration ( > 10 years, P < 0.001). This may help define a subgroup of patients with long-term persistence of GADA. The risk conferred by 1858T allele on GAD positivity was additive, and our meta-analysis also supported an additive rather than dominant effect of this variant on type I diabetes, similar to previous reports on rheumatoid arthritis and systemic lupus erythematosus.