HLA-DQA1 and HLA-DQB1 in Celiac disease predisposition: practical implications of the HLA molecular typing

• Published in: Journal of biomedical science 2012-10, Vol.19 (1), p.88-88
• Main Authors: Megiorni, Francesca, Pizzuti, Antonio
• Format: Article
• Language: English
• Subjects: Autoimmune diseases; Autoimmune Diseases - complications; Autoimmune Diseases - genetics; Celiac disease; Celiac Disease - complications; Celiac Disease - epidemiology; Celiac Disease - genetics; Cell adhesion & migration; Chromosomes; Development and progression; Diet; Disease; Disease risk; Europe; Family; Fatty acids; Female; Genetic counseling; Genetic Predisposition to Disease; Genetic screening; Genetic Testing; Genetics; Genomes; Gluten; Haplotypes; Health risk assessment; Histocompatibility antigens; HLA histocompatibility antigens; HLA typing; HLA-DQ alpha-Chains - genetics; HLA-DQ beta-Chains - genetics; HLA-DQA1; HLA-DQB1; Humans; Male; Medical research; Medicine, Experimental; Multiple sclerosis; Proteins; Review; Risk Factors; United States
• ISSN: 1423-0127; 1021-7770; 1423-0127
• DOI: 10.1186/1423-0127-19-88

Celiac disease (CD) is a multifactorial disorder with an estimated prevalence in Europe and USA of 1:100 and a female:male ratio of approximately 2:1. The disorder has a multifactorial etiology in which the triggering environmental factor, the gluten, and the main genetic factors, Human Leukocyte Antigen (HLA)-DQA1 and HLA-DQB1 loci, are well known. About 90-95% of CD patients carry DQ2.5 heterodimers, encoded by DQA1*05 and DQB1*02 alleles both in cis or in trans configuration, and DQ8 molecules, encoded by DQB1*03:02 generally in combination with DQA1*03 variant. Less frequently, CD occurs in individuals positive for the DQ2.x heterodimers (DQA1≠*05 and DQB1*02) and very rarely in patients negative for these DQ predisposing markers. HLA molecular typing for Celiac disease is, therefore, a genetic test with a negative predictive value. Nevertheless, it is an important tool able to discriminate individuals genetically susceptible to CD, especially in at-risk groups such as first-degree relatives (parents, siblings and offspring) of patients and in presence of autoimmune conditions (type 1 diabetes, thyroiditis, multiple sclerosis) or specific genetic disorders (Down, Turner or Williams syndromes).