Misplaced Pages

HLA DR3-DQ2

HLA region on chromosome 6
Nicknames
HLA DRB1*0301:DQA1*0501:DQB1*0201
Loci
Loci Gene Allele Serotype HLA-DR HLA-DRA *0101 HLA-DRB1 *0301 DR3 HLA-DRB3 *0101 DR52 HLA-DQ HLA-DQA1 *0501 HLA-DQB1 *0201 DQ2
Nodes
PopulationMaxima	Sardinia
Freq.Max	22%
Size and location
Genes	5
Chromosome	6
Location	6p21.3
Size (kbps)	300
Associated diseases
Haplotype (gene) Disease(s) DQ2.5 Coeliac disease DR3-DQ2 Juvenile diabetes DR3-DQ2 Sarcoidosis

HLA DR3-DQ2 is a double serotype that specifically recognizes cells from individuals who carry a multigene HLA DR, DQ haplotype. Certain HLA DR and DQ genes have known involvement in autoimmune diseases. DR3-DQ2, a multigene haplotype, stands out in prominence because it is a factor in several prominent diseases, namely coeliac disease and juvenile diabetes. In coeliac disease, the DR3-DQ2 haplotype is associated with highest risk for disease in first degree relatives, highest risk is conferred by DQA1*0501:DQB1*0201 homozygotes and semihomozygotes of DQ2, and represents the overwhelming majority of risk. HLA DR3-DQ2 encodes DQ2.5cis isoform of HLA-DQ, this isoform is described frequently as 'the DQ2 isoform', but in actuality there are two major DQ2 isoform. The DQ2.5 isoform, however, is many times more frequently associated with autoimmune disease, and as a result to contribution of DQ2.2 is often ignored.

The frequency of both diseases changes concerning both the environment (diet) and the frequency of the DR3-DQ2. With coeliac disease risk is increased with the consumption of Triticeae glutens, and this also increases risk in juvenile diabetes whereas other cereals also appear to play a role. More importantly the risk of disease is greatest in homozygotes and linear increases in haplotype result in several fold increases in disease risk. This increased risk is most prominent in a rare cancer, enteropathy associated T-cell lymphoma. HLA-DR3-DQ2 is found in HLA A1-B8-DR3-DQ2 haplotype in Northern Europeans (including the British Ilse, Ireland, Iceland).

Genetic Linkage

HLA DR3-DQ2 is the serotypic representation of a HLA-DRB1:DQA1:DQB1 cis-chromosomal haplotype on human 6p21.3 in a region known as the HLA complex. The DR3-DQ2 haplotype is notable because of the very strong linkage between genes that extends into the HLA-A, -B and -C regions of the HLA gene complex in northern and northwestern Europe. The linked haplotype is HLA A1-B8-DR3-DQ2 (AH8.1 in the most recent literature)

Because of its strong linkage disequilibrium, each of the genes in the haplotype are markers for probable presence of adjacent genes. However serotyping does not recognize genes, but clusters of gene products. For example, DQ2 recognizes both DQB1*0201, DQB1*0202, DQB1*0203. DQB1*0202 is not genetically linked to DQA1*0501 and its cis-haplotype isoform infrequently mediates coeliac disease or type 1 diabetes. For serotypic identification of the DQ2.5cis isoform requires the DR3 (or HLA-DR17 or HLA-DR18) and DQ2 serotypes.

An example of phenotypes that can mediate CD and T1D, the DR3-DQ2/X serotypes and the DR5-DQ7/DR7-DQ2 serotypes can mediate celiac disease with equal efficiency but the DR5-DQ7/DR7-DQ2 cannot mediate T1D as successfully as DR4-DQ8 or DR3-DQ2 (X is not DR3-DQ2 or DR7-DQ2).

Distribution

HLA DR3-DQ2 is not spread evenly among humans. It has a substantially higher frequency in the western world, except indigenous Native American (see tables). It is virtually absent in some Asian populations. It current world distribution suggest that it spread from Africa with a wave that spread late in human evolution which reached central Asia more recently, a possibility is that it spread with agrarian cultures that migrated from Africa.

Frequencies in Africa

DR3-DQ2 probably originated from Central or West Africa. DQ2.5cis haplotype is the second highest frequency haplotype in the Aka (N. Congo) and several other surrounding groups it is virtually absent in the !Kung. DQ2.5 primarily spread to the northwest and appears to have spread late in global spread of anatomically modern humans. The !Kung and Austronesians are reasonable marker populations earliest (eatward) spread out of Africa and those that spread rapidly, since the ancestors of the !Kung appear to have come from East Africa and share many Cw_B types in common with Austronesians and Northern Eurasians. DQ2.5 is at low frequencies in both of these populations, and it did not spread to Japan or the New World in pre-Columbian times. There is the possibility it spread to Arabia, but through stepwise expansion of small groups was lost from the DQ genetic repertoire.

DQ2.5 appears to be derived from DQ2.2 by gene recombination. One haplotype DQA1*0501:DQB1*0202 can be found in Africa suggesting DQB1*0201 evolved from DQB1*0202. The regions of Africa where DQ2.5 is at its highest frequencies indicate potential sources for western European haplotypes (e.g. bedoin) but also indicate recent dispersion making precise evolution difficult to interpret. Other evidence for a west African origin/expansion is seen with the probable origin of DQA1*0501 from DQA1*0505, which is at relatively high frequencies in west-central Africa.

Frequencies in Europe

In identifying DR3-DQ2 studies of DR3 and DQ8 frequencies, when DQ2.5 frequencies are not clear, are helpful. DQ8 is helpful because of the strong linkage disequilibrium (LD) of the "super B8" haplotype. Unclear genetic information has come about because of false genotyping assumptions in older studies. DQB1*0201 may be available, but most often it is given incorrectly (DQB1*0201 = DQB1*0201 + DQB1*0202 + DQB1*0203). DQA1*0501 is often given incorrectly (DQB1*0501 = DQB1*0501 + DQB1*0505). These typing errors were not fully recognized until 2000. B8 frequencies are less useful in Southern and Eastern Europe, and there is no B allele that is in strong LD with DR3-DQ2. Therefore, as one moves east and southward B8 less predictive and DRB1*03 and DQB1*0201 (if DQB1*0202 is also given) must be relied upon.

European DR3-DQ2 is ancestrally derived from Africa, probably from Southwestern Europe or the Levant (in which DQ2.5 may have undergone negative, coeliac disease, selection during the holocene). Since the last glacial maximum there appears to be two sources of DR3-DQ2. The first, propagating "super b8" is from Iberia into much of western and central Europe. The second, propagating A30-B18-DR3-DQ2, is from Africa into Sardinia, Iberia, France and Italy.

Anti-node in Western Europe. DR3-DQ2 was probably the predominant HLA haplotype in the early holocene Western and Central Europe, archaeological studies of France, particularly of the Paris Basin region indicate a cultural shift that occurs as a result of the neolithic revolution. In this region of France DR3-DQ2 specifically associated with super-B8 forms an anti-node of frequencies, whereas HLA types more common in Italy, Greece and the middle east are more common within this region of France. Other haplotypes indicate this introgression was significant over and the primary wheat farming regions of Europe.

Multiple Nodes. Because of the central location of the anti-node, the center of expansion of DR3-DQ2 with the recolonization of western Europe after the last glacial maximum has been obscured. However, the frequency is still high within the Basque of NE Spain, including some Super-B8 haplotype. The highest frequency of this node is in Western Ireland. Despite its high frequency Ireland is not likely the source of the haplotype in European, but a region that has been least disturbed by the negative selection of wheat culture and migrations. Much of Ireland was covered in glacial ice in the late paleolithic and few exploitable resources. Colonization started about 10500 years ago, whereas neolithization started about 6500 years ago and was dominated by cattle culture with some wheat and minor barley cultivation. The paleontology of Europe during the last glacial maximum suggests that the most likely places of origin are NE Iberia, Southern France and new ice-core evidence suggests that final spread northward probably occurred after Younger Dryas.

Frequencies in Asia

Based on frequencies in Central and East Asia, DR3_DQ2 appears to have spread eastward recently. Of particular interest to the West African/Central Asian comparison, not only is DQ3-DQ2.5 elevated in both places, but a linked HLA A-B haplotype, A33-B58, is found in West Africans and both the A33 and B58 alleles show more allelic and haplotype diversity in West Africa. This similarity would be remarkable if this haplotype came with migrations 50,000 to 130,000 years ago, since considerable equilibration and long range migrations are expected over this time frame. Ironically, there is no convincing route of travel between West Africa and Central Asia suggested by gene frequencies in the peoples between the two. This recent migration hypothesis is supported by HLA-A36 which shows a similar African/Central Asian bimodal distribution. One population that might have been related to this migration are non-caucasians of northern Africa.

DR3-DQ2 is notably higher in W. Mongolia, Kazakhstan and W. China. One eastern haplotype is "A33-B58" and has some punctuated distribution in Western Europe at relatively low levels, and is also in extreme disequilibrium where it is found, elsewhere. In Thailand it is elevated, particularly in the Thai Chinese, but in the south and most parts of Indonesia its frequency is zero. Elevated DR3-DQ2 levels in the Muong suggest a similar North to South spread.

DR3-DQ2 presence in the Koreans and lack thereof in the Japanese suggest a recent spread into Western Pacific Rim of Asia. By HLA, Y chromosome, or mitochondrial DNA the Japanese are about 60-85% of post-Jōmon period Korean origin, and the level of DR3-DQ2 in Japanese is about 1/10 that of Koreans suggesting that DR3-DQ2 did not spread in the Yayoi and that it spread recently with Mongol spread in Eastern Asia, it is rare both east and south of China (except in regions with strong historic migrations of Chinese), rare in Indigenous Austronesians, and isolated Indigeonous American groups.

The importance of the estimates

Currently, in assessing diseases like Coeliac disease a definite diagnosis is often not possible and statistical considerations are relied upon. The knowledge of frequencies in populations, particularly among ancestors of immigrants can aid patient and physician as to the potential risks. An example, one publication states that the western regions of Ireland have the highest coeliac disease rate in the world. Plotting the frequency of DQ2.5 from any part of Western Europe to the Irish one sees the frequency gradient progressing toward the north and west of Ireland; therefore, a high rate of coeliac disease is not unexpected in Western Ireland. People with many common ancestors from Ireland share similar risks of disease.

In the case of juvenile diabetes a clear distinction of DR3-DQ2 from DR7-DQ2 is necessary because both DR3 and DQ2 confer risk of disease. And DR3-DQ2/DR4-DQ8 individuals who have type 1 diabetes (late onset) are often mistaken for type-2 diabetes.

Associated Diseases

DR3-DQ2 is associated with probably the greatest frequency of autoimmune occurrence relative to any other haplotype. The DQA1*0501:DQB1*0201 (DQ2.5) locus confers susceptibility to Gluten Sensitive Enteropathy (GSE)and (Type 1 Diabetes) but has also been linked to other rarer autoimmune diseases like myasthenia gravis.

Type 1 diabetes

In type 1 diabetes both DR3 and DQ2 appear to play a role.

• DR3-DQ2.5 can be established to other genes like TNF-305A (TNF2) which may also increase the risk of autoimmune disease in both Coeliac Disease and Type 1 diabetes. In systemic lupus erythematosus (SLE) patients HLA DR3-DQ2.5-C4AQ0, which was strongly associated with SLE (odds ratio 2.8, 95% CI 1.7-4.5).
• A more recent paper shows that Inositol triphosphate receptor 3 gene which is ~ 1 million base pairs from DQ2.5 is also associated with Type 1 diabetes.

Sarcoidosis

A relationship between HLA and sarcoidosis has been known for 30+ years. However, the association is weak and has not been reproducible in all studies. A common serologically defined haplotype in Europeans is HLA A1-B8-DR3-DQ2.5 (see above). In non-persistent sarcoidosis this haplotype was found to be increased in sarcoidosis, and further study eliminated risk contributed by A1-Cw7-B8 indicating DR3-DQ2 haplotype contains risk of disease (OR = 11.8)

Extended linkage

• DQ2.5 is also linked to the IgA-less phenotype which may or may not increase susceptibility to diseases. This imposes a problem for understanding autoimmunity in DQ2.5, since many genes linked to disease with partial contributions are some degree of disequilibration with DQ2.5 loci and thus DQ2.5 masks genetic association via it positive association with some many diseases.

References

1. Izaabel H, Garchon H, Caillat-Zucman S, Beaurain G, Akhayat O, Bach J, Sanchez-Mazas A (1998). "HLA class II DNA polymorphism in a Moroccan population from the Souss, Agadir area". Tissue Antigens. 51 (1): 106–10. doi:10.1111/j.1399-0039.1998.tb02954.x. PMID 9459511.
2. Piancatelli D, Canossi A, Aureli A, Oumhani K, Del Beato T, Di Rocco M, Liberatore G, Tessitore A, Witter K, El Aouad R, Adorno D (2004). "Human leukocyte antigen-A, -B, and -Cw polymorphism in a Berber population from North Morocco using sequence-based typing". Tissue Antigens. 63 (2): 158–72. doi:10.1111/j.1399-0039.2004.00161.x. PMID 14705987.
3. Hajjej A, Kâabi H, Sellami M, Dridi A, Jeridi A, El borgi W, Cherif G, Elgaâïed A, Almawi W, Boukef K, Hmida S (2006). "The contribution of HLA class I and II alleles and haplotypes to the investigation of the evolutionary history of Tunisians". Tissue Antigens. 68 (2): 153–62. doi:10.1111/j.1399-0039.2006.00622.x. PMID 16866885.
4. de Pablo R, García-Pacheco J, Vilches C, Moreno M, Sanz L, Rementería M, Puente S, Kreisler M (1997). "HLA class I and class II allele distribution in the Bubi population from the island of Bioko (Equatorial Guinea)". Tissue Antigens. 50 (6): 593–601. doi:10.1111/j.1399-0039.1997.tb02917.x. PMID 9458112.
5. ^ Renquin J, Sanchez-Mazas A, Halle L, Rivalland S, Jaeger G, Mbayo K, Bianchi F, Kaplan C (2001). "HLA class II polymorphism in Aka Pygmies and Bantu Congolese and a reassessment of HLA-DRB1 African diversity". Tissue Antigens. 58 (4): 211–22. doi:10.1034/j.1399-0039.2001.580401.x. PMID 11782272.
6. Arnaiz-Villena A, Benmamar D, Alvarez M, Diaz-Campos N, Varela P, Gomez-Casado E, Martinez-Laso J (1995). "HLA allele and haplotype frequencies in Algerians. Relatedness to Spaniards and Basques". Hum Immunol. 43 (4): 259–68. doi:10.1016/0198-8859(95)00024-X. PMID 7499173.
7. ^ Kimiyoshi T, Aizawa M, Sasazuki T (1992). Proceedings of the Eleventh International Histocompatibility Workshop and Conference Held in Yokohoma, Japan, 6–13 November 1991. Oxford: Oxford University Press. ISBN 0-19-262390-7.
8. Fort M, de Stefano G, Cambon-Thomsen A, Giraldo-Alvarez P, Dugoujon J, Ohayon E, Scano G, Abbal M (1998). "HLA class II allele and haplotype frequencies in Ethiopian Amhara and Oromo populations". Tissue Antigens. 51 (4 Pt 1): 327–36. doi:10.1111/j.1399-0039.1998.tb02971.x. PMID 9583804.
9. ^ Mack S, Bugawan T, Moonsamy P, Erlich J, Trachtenberg E, Paik Y, Begovich A, Saha N, Beck H, Stoneking M, Erlich H (2000). "Evolution of Pacific/Asian populations inferred from HLA class II allele frequency distributions". Tissue Antigens. 55 (5): 383–400. doi:10.1034/j.1399-0039.2000.550501.x. PMID 10885559.
10. Michalski J, McCombs C, Arai T, Elston R, Cao T, McCarthy C, Stevens F (1996). "HLA-DR, DQ genotypes of celiac disease patients and healthy subjects from the West of Ireland". Tissue Antigens. 47 (2): 127–33. doi:10.1111/j.1399-0039.1996.tb02525.x. PMID 8851726.
11. Savage D, Middleton D, Trainor F, Taylor A, Carson M, Stevens F, McCarthy C (1992). "HLA class II frequencies in celiac disease patients in the west of Ireland". Hum Immunol. 34 (1): 47–52. doi:10.1016/0198-8859(92)90084-Z. PMID 1356956.
12. Finch T, Lawlor E, Borton M, Barnes C, McNamara S, O'Riordan J, McCann S, Darke C (1997). "Distribution of HLA-A, B and DR genes and haplotypes in the Irish population". Exp Clin Immunogenet. 14 (4): 250–63. PMID 9523161.
13. Williams F, Meenagh A, Single R, McNally M, Kelly P, Nelson M, Meyer D, Lancaster A, Thomson G, Middleton D (2004). "High resolution HLA-DRB1 identification of a Caucasian population". Hum Immunol. 65 (1): 66–77. doi:10.1016/j.humimm.2003.10.004. PMID 14700598.
14. Middleton D, Williams F, Hamill M, Meenagh A (2000). "Frequency of HLA-B alleles in a Caucasoid population determined by a two-stage PCR-SSOP typing strategy". Hum Immunol. 61 (12): 1285–97. doi:10.1016/S0198-8859(00)00186-5. PMID 11163085.
15. Sanchez-Velasco P, Gomez-Casado E, Martinez-Laso J, Moscoso J, Zamora J, Lowy E, Silvera C, Cemborain A, Leyva-Cobián F, Arnaiz-Villena A (2003). "HLA alleles in isolated populations from North Spain: origin of the Basques and the ancient Iberians". Tissue Antigens. 61 (5): 384–92. doi:10.1034/j.1399-0039.2003.00041.x. PMID 12753657.
16. Darke C, Guttridge M, Thompson J, McNamara S, Street J, Thomas M (1998). "HLA class I (A, B) and II (DR, DQ) gene and haplotype frequencies in blood donors from Wales". Exp Clin Immunogenet. 15 (2): 69–83. doi:10.1159/000019057. PMID 9691201. S2CID 46788747.
17. Schipper R, Schreuder G, D'Amaro J, Oudshoorn M (1996). "HLA gene and haplotype frequencies in Dutch blood donors". Tissue Antigens. 48 (5): 562–74. doi:10.1111/j.1399-0039.1996.tb02670.x. PMID 8988539.
18. Van der Auwera B, Schuit F, Weets I, Ivens A, Van Autreve J, Gorus F (2002). "Relative and absolute HLA-DQA1-DQB1 linked risk for developing type I diabetes before 40 years of age in the Belgian population: implications for future prevention studies". Hum Immunol. 63 (1): 40–50. doi:10.1016/S0198-8859(01)00362-7. PMID 11916169.
19. Grundschober C, Sanchez-Mazas A, Excoffier L, Langaney A, Jeannet M, Tiercy J (1994). "HLA-DPB1 DNA polymorphism in the Swiss population: linkage disequilibrium with other HLA loci and population genetic affinities". European Journal of Immunogenetics. 21 (3): 143–57. doi:10.1111/j.1744-313X.1994.tb00186.x. PMID 9098428. S2CID 29932752.
20. Krokowski M, Bodalski J, Bratek A, Boitard C, Caillat-Zucman S (1998). "HLA class II allele and haplotype distribution in a population from central Poland". European Journal of Immunogenetics. 25 (1): 5–9. doi:10.1046/j.1365-2370.1998.00086.x. PMID 9587739.
21. Jungerman M, Sanchez-Mazas A, Fichna P, Ivanova R, Charron D, Hors J, Djoulah S (1997). "HLA class II DRB1, DQA1 and DQB1 polymorphisms in the Polish population from Wielkopolska". Tissue Antigens. 49 (6): 624–8. doi:10.1111/j.1399-0039.1997.tb02810.x. PMID 9234484.
22. Pedron B, Yakouben K, Adjaoud D, Auvrignon A, Landman J, Guerin V, Leverger G, Vilmer E, Sterkers G (2005). "Listing of common HLA alleles and haplotypes based on the study of 356 families residing in the Paris, France, area: implications for unrelated hematopoietic stem cell donor selection". Hum Immunol. 66 (6): 721–31. doi:10.1016/j.humimm.2005.02.007. PMID 15993718.
23. Amar A, Kwon O, Motro U, Witt C, Bonne-Tamir B, Gabison R, Brautbar C (1999). "Molecular analysis of HLA class II polymorphisms among different ethnic groups in Israel". Hum Immunol. 60 (8): 723–30. doi:10.1016/S0198-8859(99)00043-9. PMID 10439318.
24. Arnaiz-Villena A, Karin M, Bendikuze N, Gomez-Casado E, Moscoso J, Silvera C, Oguz F, Sarper Diler A, De Pacho A, Allende L, Guillen J, Martinez Laso J (2001). "HLA alleles and haplotypes in the Turkish population: relatedness to Kurds, Armenians and other Mediterraneans". Tissue Antigens. 57 (4): 308–17. doi:10.1034/j.1399-0039.2001.057004308.x. PMID 11380939.
25. Sirén M, Sareneva H, Lokki M, Koskimies S (1996). "Unique HLA antigen frequencies in the Finnish population". Tissue Antigens. 48 (6): 703–7. doi:10.1111/j.1399-0039.1996.tb02695.x. PMID 9008314.
26. Laivoranta-Nyman S, Möttönen T, Hermann R, Tuokko J, Luukkainen R, Hakala M, Hannonen P, Korpela M, Yli-Kerttula U, Toivanen A, Ilonen J (2004). "HLA-DR-DQ haplotypes and genotypes in Finnish patients with rheumatoid arthritis". Ann Rheum Dis. 63 (11): 1406–12. doi:10.1136/ard.2003.009969. PMC 1754800. PMID 15479890.
27. Evseeva I, Spurkland A, Thorsby E, Smerdel A, Tranebjaerg L, Boldyreva M, Groudakova E, Gouskova I, Alexeev L (2002). "HLA profile of three ethnic groups living in the North-Western region of Russia". Tissue Antigens. 59 (1): 38–43. doi:10.1034/j.1399-0039.2002.590107.x. PMID 11972877.
28. Sánchez-Velasco P, Leyva-Cobián F (2001). "The HLA class I and class II allele frequencies studied at the DNA level in the Svanetian population (Upper Caucasus) and their relationships to Western European populations". Tissue Antigens. 58 (4): 223–33. doi:10.1034/j.1399-0039.2001.580402.x. PMID 11782273.
29. Grubić Z, Zunec R, Cecuk-Jelicić E, Kerhin-Brkljacić V, Kastelan A (2000). "Polymorphism of HLA-A, -B, -DRB1, -DQA1 and -DQB1 haplotypes in a Croatian population". European Journal of Immunogenetics. 27 (1): 47–51. doi:10.1046/j.1365-2370.2000.00193.x. PMID 10651851.
30. Ivanova M, Rozemuller E, Tyufekchiev N, Michailova A, Tilanus M, Naumova E (2002). "HLA polymorphism in Bulgarians defined by high-resolution typing methods in comparison with other populations". Tissue Antigens. 60 (6): 496–504. doi:10.1034/j.1399-0039.2002.600605.x. PMID 12542743.
31. Papassavas E, Spyropoulou-Vlachou M, Papassavas A, Schipper R, Doxiadis I, Stavropoulos-Giokas C (2000). "MHC class I and class II phenotype, gene, and haplotype frequencies in Greeks using molecular typing data". Hum Immunol. 61 (6): 615–23. doi:10.1016/S0198-8859(00)00115-4. PMID 10825590.
32. Uçar F, Ovali E, Pakdemir A, Alver A, Gök I, Karti S, Kalay E (2004). "HLA alleles and haplotypes in the east Black Sea Turkish population". Transplant Proc. 36 (9): 2610–4. doi:10.1016/j.transproceed.2004.10.020. PMID 15621102.
33. Hristova-Dimceva A, Verduijn W, Schipper R, Schreuder G (2000). "HLA-DRB and -DQB1 polymorphism in the Macedonian population". Tissue Antigens. 55 (1): 53–6. doi:10.1034/j.1399-0039.2000.550109.x. PMID 10703609.
34. Martinez-Laso J, Gazit E, Gomez-Casado E, Morales P, Martinez-Quiles N, Alvarez M, Martin-Villa J, Fernandez V, Arnaiz-Villena A (1996). "HLA DR and DQ polymorphism in Ashkenazi and non-Ashkenazi Jews: comparison with other Mediterraneans". Tissue Antigens. 47 (1): 63–71. doi:10.1111/j.1399-0039.1996.tb02515.x. PMID 8929714.
35. Pera C, Delfino L, Longo A, Pistillo MP, Ferrara GB (2000). "Novel associations among HLA-DQA1 and -DQB1 alleles, revealed by high-resolution sequence-based typing (SBT)". Tissue Antigens. 55 (3): 275–9. doi:10.1034/j.1399-0039.2000.550313.x. PMID 10777105.
36. Mizuki M, Ohno S, Ando H, Sato T, Imanishi T, Gojobori T, Ishihara M, Ota M, Geng Z, Geng L, Li G, Kimura M, Inoko H (1997). "Major histocompatibility complex class II alleles in Kazak and Han populations in the Silk Route of northwestern China". Tissue Antigens. 50 (5): 527–34. doi:10.1111/j.1399-0039.1997.tb02909.x. PMID 9389328.
37. ^ Mizuki N, Ohno S, Ando H, Sato T, Imanishi T, Gojobori T, Ishihara M, Goto K, Ota M, Geng Z, Geng L, Li G, Inoko H (1998). "Major histocompatibility complex class II alleles in an Uygur population in the Silk Route of Northwest China". Tissue Antigens. 51 (3): 287–92. doi:10.1111/j.1399-0039.1998.tb03104.x. PMID 9550330.
38. ^ Machulla H, Batnasan D, Steinborn F, Uyar F, Saruhan-Direskeneli G, Oguz F, Carin M, Dorak M (2003). "Genetic affinities among Mongol ethnic groups and their relationship to Turks". Tissue Antigens. 61 (4): 292–9. doi:10.1034/j.1399-0039.2003.00043.x. PMID 12753667.
39. Chimge N, Tanaka H, Kashiwase K, Ayush D, Tokunaga K, Saji H, Akaza T, Batsuuri J, Juji T (1997). "The HLA system in the population of Mongolia". Tissue Antigens. 49 (5): 477–83. doi:10.1111/j.1399-0039.1997.tb02782.x. PMID 9174140.
40. "12th International Histocompatibility Conference. Genetic diversity of HLA: functional and medical implications. Paris, France, June 9–12, 1996. Abstracts". Hum Immunol. 47 (1–2): 1–184. 1996. PMID 8909580.
41. Amirzargar A, Mytilineos J, Farjadian S, Doroudchi M, Scherer S, Opelz G, Ghaderi A (2001). "Human leukocyte antigen class II allele frequencies and haplotype association in Iranian normal population". Hum Immunol. 62 (11): 1234–8. doi:10.1016/S0198-8859(01)00320-2. PMID 11704285.
42. Lin J, Liu Z, Lv F, Fu Y, Fan X, Li S, Lu J, Liu X, Xu A (2003). "Molecular analyses of HLA-DRB1, -DPB1, and -DQB1 in Jing ethnic minority of Southwest China". Hum Immunol. 64 (8): 830–4. doi:10.1016/S0198-8859(03)00128-9. PMID 12878363.
43. ^ Uinuk-Ool T, Takezaki N, Sukernik R, Nagl S, Klein J (2002). "Origin and affinities of indigenous Siberian populations as revealed by HLA class II gene frequencies". Hum Genet. 110 (3): 209–26. doi:10.1007/s00439-001-0668-0. PMID 11935333. S2CID 20940785.
44. Rani R, Fernandez-Viña M, Stastny P (1998). "Associations between HLA class II alleles in a North Indian population". Tissue Antigens. 52 (1): 37–43. doi:10.1111/j.1399-0039.1998.tb03021.x. PMID 9714472.
45. Farjadian S, Moqadam F, Ghaderi A (2006). "HLA class II gene polymorphism in Parsees and Zoroastrians of Iran". International Journal of Immunogenetics. 33 (3): 185–91. doi:10.1111/j.1744-313X.2006.00594.x. PMID 16712649. S2CID 12667253.
46. Vu-Trieu A, Djoulah S, Tran-Thi C, Ngyuyen-Thanh T, Le Monnier De Gouville I, Hors J, Sanchez-Mazas A (1997). "HLA-DR and -DQB1 DNA polymorphisms in a Vietnamese Kinh population from Hanoi". European Journal of Immunogenetics. 24 (5): 345–56. doi:10.1046/j.1365-2370.1997.d01-107.x. PMID 9442802.
47. Zhou L, Lin B, Xie Y, Liu Z, Yan W, Xu A (2005). "Polymorphism of human leukocyte antigen-DRB1, -DQB1, and -DPB1 genes of Shandong Han population in China". Tissue Antigens. 66 (1): 37–43. doi:10.1111/j.1399-0039.2005.00418.x. PMID 15982255.
48. Lee K, Oh D, Lee C, Yang S (2005). "Allelic and haplotypic diversity of HLA-A, -B, -C, -DRB1, and -DQB1 genes in the Korean population". Tissue Antigens. 65 (5): 437–47. doi:10.1111/j.1399-0039.2005.00386.x. PMID 15853898.
49. Hatta Y, Ohashi J, Imanishi T, Kamiyama H, Iha M, Simabukuro T, Ogawa A, Tanaka H, Akaza T, Gojobori T, Juji T, Tokunaga K (1999). "HLA genes and haplotypes in Ryūkyūans suggest recent gene flow to the Okinawa Islands". Hum Biol. 71 (3): 353–65. PMID 10380372.
50. Saito S, Ota S, Yamada E, Inoko H, Ota M (2000). "Allele frequencies and haplotypic associations defined by allelic DNA typing at HLA class I and class II loci in the Japanese population". Tissue Antigens. 56 (6): 522–9. doi:10.1034/j.1399-0039.2000.560606.x. PMID 11169242.
51. Bannai M, Tokunaga K, Imanishi T, Harihara S, Fujisawa K, Juji T, Omoto K (1996). "HLA class II alleles in Ainu living in Hidaka District, Hokkaidō, northern Japan". Am J Phys Anthropol. 101 (1): 1–9. doi:10.1002/(SICI)1096-8644(199609)101:1<1::AID-AJPA1>3.0.CO;2-Z. PMID 8876810.
52. ^ Uinuk-Ool T, Takezaki N, Derbeneva O, Volodko N, Sukernik R (2004). "Variation of HLA class II genes in the Nganasan and Ket, two aboriginal Siberian populations". European Journal of Immunogenetics. 31 (1): 43–51. doi:10.1111/j.1365-2370.2004.00443.x. PMID 15009181.
53. Hadithi M, von Blomberg BM, Crusius JB, et al. (2007). "Accuracy of serologic tests and HLA-DQ typing for diagnosing celiac disease". Annals of Internal Medicine. 147 (5): 294–302. doi:10.7326/0003-4819-147-5-200709040-00003. PMID 17785484. S2CID 24275278.
54. Zhong F, McCombs C, Olson J, Elston R, Stevens F, McCarthy C, Michalski J (1996). "An autosomal screen for genes that predispose to celiac disease in the western counties of Ireland". Nat Genet. 14 (3): 329–33. doi:10.1038/ng1196-329. PMID 8896565. S2CID 23667150.
55. Jönsen A, Bengtsson A, Sturfelt G, Truedsson L (2004). "Analysis of HLA DR, HLA DQ, C4A, FcgammaRIIa, FcgammaRIIIa, MBL, and IL-1Ra allelic variants in Caucasian systemic lupus erythematosus patients suggests an effect of the combined FcgammaRIIa R/R and IL-1Ra 2/2 genotypes on disease susceptibility". Arthritis Research & Therapy. 6 (6): R557–62. doi:10.1186/ar1224. PMC 1064866. PMID 15535834.
56. Roach J, Deutsch K, Li S, Siegel A, Bekris L, Einhaus D, Sheridan C, Glusman G, Hood L, Lernmark A, Janer M (2006). "Genetic mapping at 3-kilobase resolution reveals inositol 1,4,5-triphosphate receptor 3 as a risk factor for type 1 diabetes in Sweden". American Journal of Human Genetics. 79 (4): 614–27. doi:10.1086/507876. PMC 1592562. PMID 16960798.
57. Rybicki BA, Iannuzzi MC (March 2004). "Sarcoidosis and human leukocyte antigen class I and II genes: it takes two to tango?". Am. J. Respir. Crit. Care Med. 169 (6): 665–6. doi:10.1164/rccm.2401005. PMID 15003948.
58. Grunewald J, Eklund A, Olerup O (March 2004). "Human leukocyte antigen class I alleles and the disease course in sarcoidosis patients". Am. J. Respir. Crit. Care Med. 169 (6): 696–702. doi:10.1164/rccm.200303-459OC. PMID 14656748. S2CID 16435273.
59. Schaffer F, Palermos J, Zhu Z, Barger B, Cooper M, Volanakis J (1989). "Individuals with IgA deficiency and common variable immunodeficiency share polymorphisms of major histocompatibility complex class III genes". Proc Natl Acad Sci USA. 86 (20): 8015–9. Bibcode:1989PNAS...86.8015S. doi:10.1073/pnas.86.20.8015. PMC 298204. PMID 2573059.
60. Klemola T, Savilahti E, Koskimies S, Pelkonen P (1988). "HLA antigens in IgA deficient paediatric patients". Tissue Antigens. 32 (4): 218–23. doi:10.1111/j.1399-0039.1988.tb01659.x. PMID 3217938.

External links

Coeliac Disease

• Coeliac UK Archived 2006-05-27 at the Wayback Machine (charity)
• The Celiac Disease Foundation Archived 2006-10-23 at the Wayback Machine (U.S.)
• National Digestive Diseases Clearinghouse - page on coeliac disease
• National Foundation for Celiac Awareness (U.S.)
• University of Maryland Center for Celiac Research

Type 1 Diabetes

• Children with Diabetes
• Type 1 Diabetes at the American Diabetes Association

• HLA-DQ haplotypes
• Human MHC mediated diseases
• HLA-DR haplotypes
• Human MHC haplogroups