HLA-DQ2

DQ2 is most common in Western Europe, North Africa and East Africa. Highest frequencies are observed in parts of Spain and Ireland; this distribution correlates with the frequency of two of the most prevalent autoimmune diseases. There is also an increase in DQB1*0201 in Central Asia, peaking in Kazakhstan and declining slowly west to east into China and finally Southeast Asia. DQA1*0501 : DQB1*0201. DQ2.5 is one of the most predisposing factors for autoimmune disease.DQ2.5 is encoded, often, by a haplotype associated with a large number of diseases. This haplotype, HLA A1-B8-DR3-DQ2, is associated with diseases in which HLA-DQ2 has suspect involvement. Direct involvement of DQ2 is certain in coeliac disease. Serotyping efficiency. The serotyping efficiency of HLA-DQ2 is among the highest of theantisera. DQ2 antibodies can be used to effectively type DQ2 bearing individuals, however antibody may detect DQB1*0303. The DQB1*0201 allele is genetically linked to DQA1*0501 and DRB1*03. With DQA1*0501 it forms the DQ2.5cis encoding haplotype, with DRB1*03 it becomes part of the DR3-DQ2 (DR-DQ) serologically defined haplotype. With DQA1*0501 the allele is most frequently found in coeliac disease. With DR3 this DQ2 has the second strongest linkage to Type 1 diabetes, and when paired with HLA-DQ8 is the most abundant phenotype found in late onset, 'Type1-Type2' diabetes mellitus type 1. As the incidence of coeliac disease is about 1% this allele is associated with more autoimmune disease relative to any other DQ haplotype. There are ambiguities regarding DQB1*0201 in the literature, some low resolution typing kits detect *0202 as *0201 and are presented as *0201 in the literature without distinction. DQB1*0201 in Europe is frequently found in the HLA A1-B8-DR3-DQ2 haplotype. This allele is linked to several DQA1* alleles, the linkage with DQA1*0201 forms the DQ2.2 haplotype and linkage with DQA1*0303 forms the DQ2.3 haplotype. In Africa the DQA1*0501 haplotype is also linked rarely to DQB1*0202 and may represent that ancestral form of the DQ2.5 haplotype. DQ2.5 refers to either a protein isoform and a genetic (chromosomal) haplotype. DQ2.5 isoform or heterodimer is shorthand for the cell surface receptor HLA-DQ α5β2. Frequently called 'the DQ2 heterodimer', the DQ2.5 isoform is actually one of two common DQ heterodimers, the other being DQ2.2.DQ2.5 haplotype is created by close genetic linkage of two alleles, written as a haplotype, DQA1*0501:DQB1*0201.The haplotype encodes DQ2.5cis isoform, referring to the cis arrangementof the DQA1*0501 and DQB1*0201 on the same variant of chromosome 6. The isoform can also be encoded trans-haplotype (between two sister chromosomes) forming the DQ2.5trans isoform. This isoform occurs when a person has the DQ7.5/DQ2.2 phenotype. DQ2.5 and the linked DR3 are associated with probably the greatest frequency of autoimmune occurrence relative to any other haplotypes. The haplotype is positively associated with coeliac disease, dermatitis herpetiformis, juvenile diabetes, Lambert-Eaton myasthenic syndrome (LEMS), Sjögren's syndrome, and autoimmune hepatitis (although significant proportion of the risk is secondary to coeliac disease). DR3 and/or DQ2.5 are linked to the following diseases: Moreen's ulceration, 'bout onset' multiple sclerosis, Grave's disease and systemic lupus erythematosus. DQ2.2 is shorthand for the DQ α2β2 heterodimeric isoform. The isoform is encoded almost exclusively by the DQA1*0201:DQB1*0202 haplotype. The haplotype is linked to DR7. A small percentage of coeliac disease are associated with this haplotype, and some disease causing gliadins are presented by DQ2.2. The haplotype is found at high frequencies in the Mediterranean and West Africa. The Eurasian geographic distribution of DQ2.2 is slightly greater than DQ2.5. Compared to DQ2.5, the frequency in Sardinia is low, but in Iberia it is high reaching a maximum frequency of ~30% in Northern Iberia, and half that in the British Ilses. It extends along the Mediterranean and Africa at relatively high frequency and is found in high frequencies in some Central Asian, Mongolians, and Han Chinese. It does not appear to have an indigenous presence in the West Pacific Rim or the New World and DQ2.2 presence in Southeast Asia and Indonesia is likely the result of gene flow from India and China in post-neolithic times. The haplotype shows considerable diversity in Africa and this has translated to Iberia with 2 addition haplotypes, DQA1*0303:DQB1*0202 and DR7:DQA1*0201:DQB1*0303. The expansion of DQ2.2 into Europe appears to have been slightly later or biased by some constriction between Iberia and the rest of the continent.