Martín-Pagola Ainhoa, Pérez de Nanclares Guiomar, Vitoria Juan C, Bilbao J Ramón, Ortiz Lourdes, Zubillaga Paul, Castaño Luis
Endocrinology & Diabetes Research, Hospital de Cruces, Barakaldo, Spain.
J Pediatr Gastroenterol Nutr. 2003 Aug;37(2):142-5. doi: 10.1097/00005176-200308000-00011.
Celiac disease (CD) is an autoimmune disorder caused by intolerance to ingested gluten that develops in genetically susceptible individuals. The contribution of human leukocyte antigen (HLA) genes to the genetic risk to CD has been known for a long time; however, non-HLA genetic factors are likely to be required for the development of the disease. Several studies have associated the CD28/CTLA4 region on chromosome 2q33 with the disease in different populations. The CTLA4 gene encodes a receptor involved in the control of T-cell proliferation and mediates T-cell apoptosis. AIM To determine the contribution of two polymorphisms of the CTLA4 to the disease: the A/G dimorphism at position +49 in exon 1 and the (AT)(n) microsatellite in the 3' untranslated region.
Forty-one celiac families of Basque origin (43 patients with CD and 80 first-degree relatives).
Restriction enzyme digestion of polymerase chain reaction amplified genomic DNA for the A/G dimorphism and polymerase chain reaction followed by high-resolution electrophoresis for the (AT)(n) microsatellite. For disease association studies, the Affected Family Based Controls approach was used.
The frequency of the A allele of 49 A/G polymorphism was 67.47% in the celiac allele group compared with 70.13% in the Affected Family Based Controls group. These differences were not significant. Analysis of the (AT)(n) polymorphism identified 17 different alleles, ranging from 262 to 312 bp in length, but no allele was significantly associated with the disease.
Our results did not show any evidence of association of any of the CTLA4 gene polymorphisms with the disease. This may result from population-specific differences in genetics and environmental susceptibility to CD.
乳糜泻（CD）是一种自身免疫性疾病，由对摄入麸质不耐受引起，发生于具有遗传易感性的个体。人类白细胞抗原（HLA）基因对CD遗传风险的作用早已为人所知；然而，疾病的发生可能还需要非HLA遗传因素。多项研究已将2q33染色体上的CD28/CTLA4区域与不同人群的该疾病关联起来。CTLA4基因编码一种参与控制T细胞增殖的受体，并介导T细胞凋亡。目的：确定CTLA4的两种多态性对该疾病的作用：外显子1中第49位的A/G二态性以及3'非翻译区的（AT）（n）微卫星。
41个巴斯克血统的乳糜泻家族（43例CD患者和80名一级亲属）。
对聚合酶链反应扩增的基因组DNA进行限制性酶切以检测A/G二态性，对（AT）（n）微卫星进行聚合酶链反应后进行高分辨率电泳。对于疾病关联研究，采用基于患病家系对照的方法。
在乳糜泻等位基因组中，49 A/G多态性的A等位基因频率为67.47%，而在基于患病家系对照的组中为70.13%。这些差异不显著。对（AT）（n）多态性的分析鉴定出17个不同的等位基因，长度在262至312 bp之间，但没有等位基因与该疾病显著相关。
我们的结果未显示CTLA4基因的任何多态性与该疾病存在关联的证据。这可能是由于CD在遗传和环境易感性方面存在人群特异性差异所致。
