What does my HLA genotype mean?
The celiac disease genotyping test offered by Genetrace detects three HLA variations (alleles) that are linked to an increased risk of celiac disease. Nearly 100% of celiac patients carry one or more of these alleles, but these alleles are also present in at least 20% of the general, unaffected population. This DNA test is very useful to essentially rule out a celiac diagnosis (if the risk-alleles are absent) or indicate your level of celiac risk. It is recommended that individuals who are at a high risk of celiac disease obtain further testing for celiac disease. The HLA genes are located on chromosome 6 and encode components of the human leukocyte antigen (HLA) complex. This complex is an important part of the immune system and helps to distinguish between harmless proteins (from self and the environment e.g. diet) and foreign proteins from harmful bacteria and viruses. The HLA-DQA1 gene encodes the alpha subunit of the HLA-DQ complex and the HLA-DQB1 gene encodes the beta subunit, and together these subunits display foreign proteins to the immune system. These genes vary significantly between individuals and some genetic variants (alleles) are associated with various health conditions. HLA-DQA1*05, HLA-DQB1*02 and HLA-DQB1*03:02 are three alleles that increase the risk of celiac disease. The DQ2 and DQ8 complexes are formed from the subunits encoded from these risk-alleles. These complexes bind to and display the harmless gliadin fraction from gluten, initiating an aberrant immune response. We inherit two copies of each HLA gene – one from each parent. We may inherit two identical copies, known as homozygous at that gene locus, or two different alleles, known as heterozygous. The DQ2 complex (or more specifically DQ2.5) is formed from DQA1*05 and DQB1*02 subunits, and is associated with the highest risk of celiac disease, especially if an individual is homozygous for either both HLA-DQA1*05 and HLA-DQB1*02, or heterozygous for HLA-DQA1*05 but homozygous for HLA-DQB1*02. Even individuals who have a single copy of each of these two risk-alleles (heterozygous) are at an increased risk of developing celiac disease. The DQ8 complex is formed from DQA1*03 and DQB1*03:02 subunits. The genetic test offered here only detects the HLA-DQB1*03:02 allele but this is always inherited with one of the HLA-DQA1*03 alleles. Hence, if you carry one copy of HLA-DQB1*03:02, you will also carry one copy of HLA-DQA1*03. Both DQ8 heterozygotes and homozygotes have an increased risk of celiac disease. References: Liu E et al. (2014). Risk of Pediatric Celiac Disease According to HLA Haplotype and Country. N Engl J Med. 371: 42-49. Megiorni F, Mora B, Bonamico M, Barbato M, Nenna R, Maiella G, Mazzilli MC (2009). HLA-DQ and risk gradient for celiac disease. Hum Immunol 70(1): 55-59. Pietzak MM, Schofield TC, McGinniss MJ, Nakamura RM (2009).Stratifying risk for celiac disease in a large at-risk United States population by using HLA alleles. Clin Gastroenterol Hepatol. 7(9): 966-71.Genovate Laboratories2017-04-06T19:04:51+00:00