Genetics Of Gluten Intolerance

Abstract

Celiac disease, or extreme gluten intolerance, is an autoimmune disease that primarily causes damage to the small intestine. It is caused by dietary intake of gluten in genetically predisposed individuals. The presentation of celiac disease consists of digestive tract symptoms, mainly diarrhea and subsequent weight loss. Other related symptoms and findings are iron deficiency anemia, decreased bone density, and some nonspecific neurological symptoms. In the recent past, the diagnosis of celiac disease was made based on specific serological tests, small intestinal mucosa biopsy results, and fading away of symptoms after gluten-free diet is applied. After the identification of the disease-specific genes HLA-DQ2 and DQ8 , genetic testing was considered the gold standard for the diagnosis of celiac disease, because the presence of a specific genotype is a prerequisite for the development of this disease. Risk variants of HLA-DQ2 and DQ8 are found in about 30% of the general European population. Determining the genetic status allows adequate subsequent clinical decisions. The lack of genetic variants predisposing to celiac disease leads to the exclusion of the diagnosis, while the detection of high-risk variant(s) in an individual prompts additional diagnostic steps through a number of serological and invasive tests. The introduction of genetic analysis has led to a significant reduction in the number of invasive intestinal tests (biopsies). The purpose of this article is to present the current practical approach in the diagnosis of celiac disease, which includes mandatory genetic analysis, and to explain the nature of this autoimmune disease from a genetic point of view.