BackgroundCeliac 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 theCD28/CTLA4region on chromosome 2q33 with the disease in different populations. TheCTLA4gene encodes a receptor involved in the control of T-cell proliferation and mediates T-cell apoptosis.AimTo determine the contribution of two polymorphisms of theCTLA4to the disease: the A/G dimorphism at position +49 in exon 1 and the (AT)nmicrosatellite in the 3´ untranslated region.PatientsForty-one celiac families of Basque origin (43 patients with CD and 80 first-degree relatives).MethodsRestriction 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)nmicrosatellite. For disease association studies, the Affected Family Based Controls approach was used.ResultsThe 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)npolymorphism identified 17 different alleles, ranging from 262 to 312 bp in length, but no allele was significantly associated with the disease.ConclusionsOur results did not show any evidence of association of any of theCTLA4gene polymorphisms with the disease. This may result from population-specific differences in genetics and environmental susceptibility to CD.