title: No association of CTLA4 gene with celiac disease in the Basque population.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Forty-one celiac families of Basque origin (43 patients with CD and 80 first-degree relatives).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Endocrinology & Diabetes Research, Hospital de Cruces, Barakaldo, Spain.
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Martín-Pagola
authors.forename: Guiomar
authors.initials: G
authors.lastname: Pérez de Nanclares
authors.forename: Juan C
authors.initials: JC
authors.lastname: Vitoria
authors.forename: J Ramón
authors.initials: JR
authors.lastname: Bilbao
authors.forename: Lourdes
authors.initials: L
authors.lastname: Ortiz
authors.forename: Paul
authors.initials: P
authors.lastname: Zubillaga
authors.forename: Luis
authors.initials: L
authors.lastname: Castaño
mesh_terms: D000293:Adolescent; D000483:Alleles; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D018106:CD28 Antigens / Q000235:genetics; D060908:CTLA-4 Antigen; D002446:Celiac Disease / Q000235:genetics* / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000032:analysis*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D018895:Microsatellite Repeats; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D004247:DNA