HLA-DQ7 (DQ7) is an
HLA-
DQ serotype that recognizes the common HLA DQB1*0301
and the less common HLA DQB1*0304 gene products. DQ7 is a form of 'split antigen' of the broad antigen group
DQ3 which also contains
DQ8 and
DQ9.
DQ7 is linked by haplotype to a number of DQA1 (DQ alpha chain) genes, producing in cis-haplotype form, a large number of DQ αβ isoforms. These DQ alpha chains are also known to form transhaplotype isomers with other HLA-DQ.
DQ7 is linked to the following alpha chains genes (DQA1*)
* 03 – *0301, *0302, *0303
* 0401
* 0505
* 0601
Serology
Serotyping efficiency. The serotyping efficiency of DQ7 toward DQB1*0301 is reasonably good, but still results in some false negatives, for *0304 the typing efficiency is poor and cross-reaction with DQ8 is relatively high.
Alleles
DQB1*0301
DQB1*0301 is the major DQ7 allele
DQB1*0301 appears to be associated with lupus anticoagulant.
DQB1*0304
DQB1*0304 is the minor DQ7 allele
Haplotypes
DQ haplotypes of this serotype are formed between the cis-chromosomal genes of the DQA1 locus.
This includes DQA1*0301, *0302, *0303, *0401, *0505, *0601.
There is a rather large degree of disequilibration about DQA1*0301 suggesting that this is one of the older and more established
HLA DQB1* alleles in Eurasia. The intron structure of DQB1 suggest that DQB1*0301 DQB1*0302/*0303 split occurred before DQB1*0302/*0303, the distribution of *03 in Africa suggest that recombination DQA1*03:DQB1*0301 are primarily the result of recombination events that have occurred in Africa. A recent study of ''myasthenia gravis'' in Houston confirms the presence of A*0505:B*0301 in Nigeria. B1*0301 and A1*03 haplotypes are found at relatively high frequencies in SE Asia and Austronesia, also indicating that it is well established in the exo-African population.
DQ7.3
The DQ7.3 haplotype can be formed by DQA1*0301:DQB1*0301, DQA1*0302:DQB1*0301, DQA1*0303:DQB1*0301. In the west, the DQA1*0303:DQB1*0301 haplotype appears to be more common.
The gene products of all 3 function similarly and subunits are interchangeable. In the literature, older DNA tests recognize DQA1*0303 as DQA1*0302, and still oldest DNA tests recognize all three as DQA1*03 or DQA1*0301.
DQA1*0303:DQB1*0301 may be involved in narcolepsy.
DQ7.3 appears to be associated with oral ulcerations and gingival disease
DQ7.4
DQA1*0401:DQB1*0301 (DQ7.4) This haplotype is found in Siberia, Africa but also at low levels in Western Europe.
DQ7.5
DQA1*
0505:DQB1*0301 (DQ7.5) was gene-typed as DQA1*
0501:DQB1*0301 until it was recognized that there was amino acid sequence variant in the preprocessed DQA1* gene product (proto-α-chain
polypeptide encoded DQA1*0505). This proto-alpha, once processed, is identical to the DQA1*0501 encoded α-chain once it is processed. Almost 100% of DQ7.5 haplotypes carry the DQA1*0505 allele.
The DR5-DQ7.5 is common in the Southeastern Europe and the
Levant
The Levant () is an approximate historical geographical term referring to a large area in the Eastern Mediterranean region of Western Asia. In its narrowest sense, which is in use today in archaeology and other cultural contexts, it is eq ...
, with DQ7.5 reaching a
haplotype
A haplotype ( haploid genotype) is a group of alleles in an organism that are inherited together from a single parent.
Many organisms contain genetic material ( DNA) which is inherited from two parents. Normally these organisms have their DNA or ...
frequency of 40% in
Lebanon
Lebanon ( , ar, لُبْنَان, translit=lubnān, ), officially the Republic of Lebanon () or the Lebanese Republic, is a country in Western Asia. It is located between Syria to the north and east and Israel to the south, while Cyprus li ...
. Its high level is probably not by chance, the haplotype appears to protect against
juvenile diabetes
Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar f ...
, which appears to be more common among cereal eating peoples.
Cereal
A cereal is any Poaceae, grass cultivated for the edible components of its grain (botanically, a type of fruit called a caryopsis), composed of the endosperm, Cereal germ, germ, and bran. Cereal Grain, grain crops are grown in greater quantit ...
s were first domesticated in the Near and
Middle East
The Middle East ( ar, الشرق الأوسط, ISO 233: ) is a geopolitical region commonly encompassing Arabian Peninsula, Arabia (including the Arabian Peninsula and Bahrain), Anatolia, Asia Minor (Asian part of Turkey except Hatay Pro ...
more than 10,000 years ago and selection may explain DQ7.5's higher frequencies. (See:
Triticeae
Triticeae is a botanical tribe within the subfamily Pooideae of grasses that includes genera with many domesticated species. Major crop genera found in this tribe include wheat (see wheat taxonomy), barley, and rye; crops in other genera includ ...
)
The processed alpha subunit of DQA1*0505 is identical to that of DQA1*0501, but some slight differences in the association with autoimmune disease are observed, possibly as a result of linked DR and DQB1 genes. DQA1*0505 can play into celiac disease under two circumstances. First it can increase risk when
DQ2.5 is present, although current studies indicate that it marginally increases risk relative to DQB1*0202 in DQ2.5 cis haplotype. DQA1*0505, without
DQ2, is found in a small percentage of coeliac disease (without DQ2 or DQ8).
DQ7.5 is found also high in frequency in the new world, but with
DR types less commonly encountered in the old world. DQA1*05 allele is not clear in the new world. DQB1*0301 may be under current positive selection in the human population, at least in areas where DQ2.5 and DQ8 are high, as it confers resistance to type 1 diabetes. For hepatitis type B, DQ7 is associated with persistence but for C, DQ7 is associated with clearance.
DQA1*0505, DQB1*0301 appear to increase the risk for melanoma in the Spanish population however this may have a linkage to more recent fair skinned migrants. DQB1*0301 is also associated with allergic fungal
sinusitis
Sinusitis, also known as rhinosinusitis, is inflammation of the mucous membranes that line the sinuses resulting in symptoms that may include thick nasal mucus, a plugged nose, and facial pain. Other signs and symptoms may include fever, head ...
, human
papillomavirus
''Papillomaviridae'' is a family of non- enveloped DNA viruses whose members are known as papillomaviruses. Several hundred species of papillomaviruses, traditionally referred to as "types", have been identified infecting all carefully inspected ...
(HPV) induced
warts
Warts are typically small, rough, hard growths that are similar in color to the rest of the skin. They typically do not result in other symptoms, except when on the bottom of the feet, where they may be painful. While they usually occur on the ...
, limited cutaneous systemic
sclerosis in Africans, and
primary sclerosing cholangitis
Primary sclerosing cholangitis (PSC) is a long-term progressive disease of the liver and gallbladder characterized by inflammation and scarring of the bile ducts, which normally allow bile to drain from the gallbladder. Affected individuals may ha ...
in Southern Europeans. DQB1*0301 is also predisposing in
narcolepsy
Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affect ...
.
DQB1*0301 does not to play a role in any frequently occurring autoimmune disease and its presence in the near east and suppressed frequencies of coeliac disease and Type 1 diabetes in these regions is suggestive that it has a positive selection in Post-
Mesolithic
The Mesolithic (Greek: μέσος, ''mesos'' 'middle' + λίθος, ''lithos'' 'stone') or Middle Stone Age is the Old World archaeological period between the Upper Paleolithic and the Neolithic. The term Epipaleolithic is often used synonymous ...
cereal based societies in the Western Eurasia.
DQB1*0301 appears to be more associated with early onset myasthenia
gravis in Japanese than DQ8, and was also found along with DQB1*0304 to be associated with Chinese MG. DQ7 or associated DR types may play a role in rheumatoid arthritis. In celiac disease the DQ7 (A*0505/1) can mediate celiac disease when HLA DQ2.2 is also present. HLA DQB1*0301 in Turks is associated with Thymoma but the risk may be associated with HLA class I loci.
DQ7.6
DQA1*0601:DQB1*0301 (DQ7.6) is a globally rare haplotype, however it is found at high frequencies in the South Pacific and along the West Pacific rim. DQB1*0301 appears to be uniquely linked to DQA1*0601. DQ7.6 is positively associated with
asthma
Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, cou ...
,
pauciarticular juvenile arthritis without
anti-nuclear antibodies
Antinuclear antibodies (ANAs, also known as antinuclear factor or ANF) are autoantibodies that bind to contents of the cell nucleus. In normal individuals, the immune system produces antibodies to foreign proteins (antigens) but not to human prote ...
,
DQ7.6 is negatively associated (Protective against) juvenile diabetes,
liver and spleen disease in ''
Schistosoma japonicum
''Schistosoma japonicum'' is an important parasite and one of the major infectious agents of schistosomiasis. This parasite has a very wide host range, infecting at least 31 species of wild mammals, including 9 carnivores, 16 rodents, one prima ...
'' infection,
pulmonary tuberculosis
Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...
.
References
{{DEFAULTSORT:Hla-Dq7
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