title: CTLA-4 +49 A/G dimorphism in Italian patients with celiac disease.
abstract: The chromosome region 2q33, which contains the cytotoxic T lymphocyte antigen-4 (CTLA-4) gene, has been reported in linkage and association with celiac disease (CD). In the present work we have tested the association between the polymorphism of the CTLA-4 exon 1 and susceptibility to CD in an Italian population, using case-control and family-based approaches. The +49 A/G dimorphism was analyzed in 86 patients, 144 ethnically matched controls, and 113 nuclear families by the polymerase chain reaction-restriction fragment length polymorphism method. A significantly higher frequency of the CTLA-4 +49A allele was observed in patients when compared with controls (p = 3 x 10(-2)). The segregation analysis in the 113 trios showed a preferential transmission of the A allele to the probands (chi(2)(TDT) = 4.85). When the patients were stratified according to the presence/absence of the high-risk human leukocyte antigen-DQ2 heterodimer, a significant difference was observed between the two groups, that is, the A allele was increased in the subjects without the DQ2 heterodimer (88.9% vs 73.5%, p = 8.3 x 10(-3)). The A allele was transmitted from heterozygous parents to eight of nine DQ2-dimer-negative patients. These data support CTLA-4 as a predisposing gene for CD in an Italian population with a prominent role in patients not carrying the high-risk human leukocyte antigen-DQ2 molecules.
authors.affiliation: Department of Experimental Medicine and Pathology, Institute of Clinical Pediatrics, University of Rome La Sapienza, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Mora
authors.forename: Margherita
authors.initials: M
authors.lastname: Bonamico
authors.forename: Paola
authors.initials: P
authors.lastname: Indovina
authors.forename: Francesca
authors.initials: F
authors.lastname: Megiorni
authors.forename: Mirella
authors.initials: M
authors.lastname: Ferri
authors.forename: Maria C
authors.initials: MC
authors.lastname: Carbone
authors.forename: Elsa
authors.initials: E
authors.lastname: Cipolletta
authors.forename: Maria C
authors.initials: MC
authors.lastname: Mazzilli
mesh_terms: D019943:Amino Acid Substitution; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics* / Q000502:physiology; D001327:Autoimmune Diseases / Q000453:epidemiology / Q000235:genetics*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D002446:Celiac Disease / Q000453:epidemiology / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D003062:Codon / Q000235:genetics; D005091:Exons / Q000235:genetics; D005787:Gene Frequency; D005802:Genes, MHC Class II; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics; D006801:Humans; D007558:Italy / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D021382:Protein Sorting Signals / Q000235:genetics
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D003062:Codon; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D021382:Protein Sorting Signals