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What are the HLA-DQA1 and HLA-DQB1 genes?

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There are more than 200 HLA genes, which are located on chromosome 6 and encode components of the human leukocyte antigen (HLA) complex. The HLA complex is an important part of the immune system, helping distinguish between harmless proteins (from self, diet or environment) and harmful foreign proteins from viruses and bacteria. The protein encoded by the HLA-DQA1 and HLA-DQB1 genes form a complex together to display foreign proteins to the immune system in order to trigger a response against the foreign invader. This HLA-DQA1 + HLA-DQB1 complex is also important to develop self-tolerance in children. However, in celiac-affected people, this complex also binds to and displays the harmless gliadin fraction from gluten, initiating an aberrant immune response.

Variation in the HLA-DQA1 and HLA-DQB1 Genes

HLA genes vary significantly between individuals and several hundred different versions (or alleles) of the HLA-DQA1 and HLA-DQB1 genes have been identified. Each allele is allocated a particular number and specific HLA alleles are associated with various health conditions. The majority (90-95%) of celiac-affected individuals carry the DQ2 heterodimer, which is complex formed from HLA-DQA1*05 and HLA-DQB1*02. 5-10% of celiac-affected individuals carry the DQ8 heterodimer, which is a complex formed from HLA-DQB1*03.02 and HLA-DQA1*03. These complexes recognize the gliadin fraction from gluten and display this foreign protein to the immune system, initiating an immune response.

Patients that have the high-risk HLA-DQB1*02 allele and also have the high-risk HLA-DQA1*05 allele have the DQ2 haplotype (or more specifically the DQ2.5 haplotype) and are at the greatest risk of developing celiac disease and experiencing severe complications.

The high-risk HLA-DQB1*0302 allele is always inherited with one of the HLA-DQA1*03 alleles due to linkage disequilibrium and this produces the DQ8 haplotype. Those with the DQ8 haplotype have an increased risk of celiac disease but the risk is not as high as those that carry the DQ2 haplotype.

 

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