Fung E Y M G, Smyth D J, Howson J M M, Cooper J D, Walker N M, Stevens H, Wicker L S, Todd J A
Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
Genes Immun. 2009 Mar;10(2):188-91. doi: 10.1038/gene.2008.99. Epub 2008 Dec 25.
As a result of genome-wide association studies in larger sample sets, there has been an increase in identifying genes that influence susceptibility to individual immune-mediated diseases, as well as evidence that some genes are associated with more than one disease. In this study, we tested 17 single nucleotide polymorphisms (SNP) from 16 gene regions that have been reported in several autoimmune diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), ankylosing spondylitis (AS) and Crohn's disease (CD) to determine whether the variants are also associated with type 1 diabetes (T1D). In up to 8010 cases and 9733 controls we found some evidence for an association with T1D in the regions containing genes: 2q32/STAT4, 17q21/STAT3, 5p15/ERAP1 (ARTS1), 6q23/TNFAIP3 and 12q13/KIF5A/PIP4K2C with allelic P-values ranging from 3.70 x 10(-3) to 3.20 x 10(-5). These findings extend our knowledge of susceptibility locus sharing across different autoimmune diseases, and provide convincing evidence that the RA/SLE locus 6q23/TNFAIP3 is a newly identified T1D locus.
在更大样本集的全基因组关联研究中，已发现越来越多影响个体免疫介导疾病易感性的基因，并且有证据表明一些基因与不止一种疾病相关。在本研究中，我们检测了来自16个基因区域的17个单核苷酸多态性（SNP），这些基因区域已在包括类风湿性关节炎（RA）、系统性红斑狼疮（SLE）、多发性硬化症（MS）、强直性脊柱炎（AS）和克罗恩病（CD）在内的多种自身免疫性疾病中被报道，以确定这些变异是否也与1型糖尿病（T1D）相关。在多达8010例病例和9733例对照中，我们发现包含以下基因的区域与T1D存在关联的一些证据：2q32/STAT4、17q21/STAT3、5p15/ERAP1（ARTS1）、6q23/TNFAIP3和12q13/KIF5A/PIP4K2C，等位基因P值范围为3.70×10⁻³至3.20×10⁻⁵。这些发现扩展了我们对不同自身免疫性疾病间易感性位点共享的认识，并提供了令人信服的证据，证明RA/SLE位点6q23/TNFAIP3是一个新发现的T1D位点。
