title: High-risk genotypes HLA-DR3-DQ2/DR3-DQ2 and DR3-DQ2/DR4-DQ8 in co-occurrence of type 1 diabetes and celiac disease.
abstract: Shared susceptibility alleles in the HLA region contribute to the co-existence of type 1 diabetes (T1D) and celiac disease (CD). The aim of our study was to identify HLA genotype variations that influence co-occurrence of T1D and CD (T1D + CD) and the order of their onset. Totally 244 patients, 67 with T1D, 68 with CD and 69 with T1D + CD, (split into "T1D first" and "CD first"), were analyzed. Control group consisted of 130 healthy unrelated individuals. Two-tailed Fisher's exact test was used for statistical analysis. The genetic background of Slovenian CD patients resembled more northern than southern European populations with DR3-DQ2/DR3-DQ2 (odds ratio [OR] = 19.68) conferring the highest risk. The T1D + CD was associated with DR3-DQ2/DR3-DQ2 (OR = 45.53) and even more with DR3-DQ2/DR4-DQ8 (OR = 93.76). DR3-DQ2/DR7-DQ2 played a neutral role in susceptibility for T1D + CD. The order of the onset of T1D or CD in patients with co-occurring diseases was not influenced by HLA risk genotype profile. DR3-DQ2/DR3-DQ2 was associated with an increased risk for developing CD in patients with T1D, whereas patients with CD carrying DR3-DQ2/DR4-DQ8 were at higher risk for developing T1D. In addition to other genetic factors including HLA class I alleles present on DR3-DQ2 extended haplotype, the second extended haplotype may moderate the risk for T1D + CD conferred by DR3-DQ2. Our results suggested that individuals carrying high-risk genotypes DR3-DQ2/DR3-DQ2 or DR3-DQ2/DR4-DQ8 would more likely develop both T1D and CD than either disease alone.
authors.affiliation: a Department of Pediatric Endocrinology , Diabetes and Metabolic Diseases, UMC - University Children's Hospital , Ljubljana , Slovenia .
authors.forename: Darja
authors.initials: D
authors.lastname: Smigoc Schweiger
authors.affiliation: b Blood Transfusion Center of Slovenia, Tissue Typing Centre , Ljubljana , Slovenia .
authors.forename: Andrijana
authors.initials: A
authors.lastname: Mendez
authors.affiliation: b Blood Transfusion Center of Slovenia, Tissue Typing Centre , Ljubljana , Slovenia .
authors.forename: Sabina
authors.initials: S
authors.lastname: Kunilo Jamnik
authors.affiliation: a Department of Pediatric Endocrinology , Diabetes and Metabolic Diseases, UMC - University Children's Hospital , Ljubljana , Slovenia .
authors.forename: Nina
authors.initials: N
authors.lastname: Bratanic
authors.affiliation: a Department of Pediatric Endocrinology , Diabetes and Metabolic Diseases, UMC - University Children's Hospital , Ljubljana , Slovenia .
authors.forename: Natasa
authors.initials: N
authors.lastname: Bratina
authors.affiliation: a Department of Pediatric Endocrinology , Diabetes and Metabolic Diseases, UMC - University Children's Hospital , Ljubljana , Slovenia .|c Faculty of Medicine , University of Ljubljana , Ljubljana , Slovenia , and.
authors.forename: Tadej
authors.initials: T
authors.lastname: Battelino
authors.affiliation: c Faculty of Medicine , University of Ljubljana , Ljubljana , Slovenia , and.|d Department of Gastroenterology , Hepatology and Nutrition, UMC - University Children's Hospital , Ljubljana , Slovenia.
authors.forename: Jernej
authors.initials: J
authors.lastname: Brecelj
authors.affiliation: b Blood Transfusion Center of Slovenia, Tissue Typing Centre , Ljubljana , Slovenia .
authors.forename: Blanka
authors.initials: B
authors.lastname: Vidan-Jeras
mesh_terms: D000483:Alleles; D015551:Autoimmunity / Q000235:genetics; D002446:Celiac Disease / Q000150:complications* / Q000209:etiology*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000209:etiology*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D012306:Risk
chemical_list: D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens
keywords: Autoimmune diseases; Slovenian population; genetic susceptibility; major histocompatibility complex; order of onset