HLA-A68

HLA-A68 (A68) is a human leukocyte antigen serotype within HLA-A serotype group. The serotype is determined by the antibody recognition of α⁶⁸ subset of HLA-A α-chains. For A68, the alpha "A" chain are encoded by the HLA-A*68 allele group and the β-chain are encoded by B2M locus.[1] A68 and A*68 are almost synonymous in meaning. A68 is a split antigen of the broad antigen serotype A28. A68 is a sister serotype of A69.

Further information: History and naming of human leukocyte antigens

HLA-A68
(MHC Class I, A cell surface antigen)
Rendering or 2hla​ showing A*6801 (cyan) and Beta-2 microglobulin (rose). There is no bound peptide in this image.
About
Protein	transmembrane receptor/ligand
Structure	αβ heterodimer
Subunits	HLA-A*68--, β2-microglobulin
Older names	A28
Subtypes
Subtype allele Available structures Aw68.1 *6801 2hla​, 1tmc​, 1hsb​ Aw68.2 *6802 - *6803 {{{cNick4}}} *68{{{cAllele4}}}
Rare alleles
Subtype allele Available structures - *6805 {{{rnick2}}} *68{{{rallele2}}} {{{rnick3}}} *68{{{rallele3}}}
Alleles link-out to IMGT/HLA database at EBI

A68 is more common in North America.

Serotype

A68 recognition of some HLA A*68 gene products[2]

A*68	A68	A28	A69	Sample
allele	%	%	%	size (N)
*6801	27	63	0	2736

A68 is poor, with low specific detection, high non-specific identification by A28.

Disease associations

By allele

A*68 is associated with higher viral load in HIV.[3][4] A68 may be protective against symptomatic heart disease in Chaga's cardiomyopathy.[5]

Allele frequencies

HLA A*6801 frequencies

Study population	Freq.  (in %)[6]
Brazil Terena	25.0
Mexico Sonora Seri	19.7
USA Alaska Yupik Natives	15.5
Mexico Mixtec Oaxaca	13.7
India Khandesh Pawra	12.0
Mexico Zaptotec Oaxaca	11.2
Burkina Faso Mossi	9.4
Mexico Chihuahua State Ta…	9.1
Ecuador Cayapa	9.0
South Africa Natal Tamil	8.0
Pakistan Sindhi	7.7
India Mumbai Marathas	7.5
Pakistan Kalash	7.5
India Tamil Nadu Nadar	7.4
Senegal Niokholo Mandenka	7.0
Georgia Tibilisi Kurds	6.7
Georgia Svaneti Svans	6.3
Mexico Mestizos	6.1
India West Bhils	6.0
Portugal Centre	6.0
Belgium	5.7
Mexico Mixe Oaxaca	5.6
Saudi Arabia Guraiat and …	5.6
USA North American Native…	5.6
USA South Texas Hispanics	5.2
Cameroon Pygmy Baka	5.0
Cape Verde Northwestern I…	4.8
Georgia Tibilisi Georgian…	4.8
Croatia	4.7
Finland	4.5
Scotland Orkney	4.4
Oman	4.3
Morocco 'berber' Nador Me…	4.2
Australia New South Wales	4.1
USA African America	4.0
China Inner Mongolia	3.9
Guadalajara Mestizos (2)	3.9
Cameroon Sawa	3.8
Mali Bandiagara	3.6
Tunisia	3.5
India Andhra Pradesh Goll…	3.4
Ireland South	3.4
Cameroon Beti	3.2
Pakistan Baloch	3.2
Burkina Faso Fulani	3.1
India West Coast Parsis	3.0
Israel Arab Druse	3.0
Japan Ainu Hokkaido	3.0
South African Natal Zulu	3.0
Sudanese	3.0
USA Caucasian	3.0
India North Hindus	2.9
Pakistan Brahui	2.9
Uganda Kampala	2.8
Iran Baloch	2.7
Ireland Northern	2.7
Romanian	2.6
USA Hispanic	2.6
Brazil	2.5
France South East	2.4
Guinea Bissau	2.3
Spain Catalonia Girona	2.3
China Beijing	2.2
France Corsica	2.0
Singapore Javanese Indone…	2.0
USA South Dakota Lakota S…	2.0
Bulgaria	1.8
Mongolia Buriat	1.7
USA Arizona Pima	1.7
Spain Eastern Andalusia	1.5
Kenya	1.4
Cameroon Bamileke	1.3
Zimbabwe Harare Shona	1.3
Russia Tuva (2)	1.1
Allele frequencies presented, only

A68 can be subdivided into 3 alleles, *6801, *6802, *6803. *6801 can also be subdivided into *680101 and *680102 (previously called *68011 and *68012).

A*6801

A*6801 is higher in certain Native American groups, South Asian peoples, African peoples, however *6801 is at low levels in most of SE Asia, particularly the indigeonous populations. This is also reflected by low levels along the West Pacific Rim including Japan. The hiatus of *6801 breaks in Northern Japan with the 3% frequency found in the Ainu, which continues to increase with Arctic peoples and falls of in Native Americans. Whereas in the Western Eurasia's northern regions, A*6801 falls off. In both Africa and the New World both A*680101 and A*680102 can be found.[7] Although in the New World A*680102 is more prevalent.

HLA A*6802 frequencies

		freq
ref.	Population	(%)
[8]	Yucpa (Venezuela)	37.2
[9]	Nandi (Kenya)	11.6
[10]	Kenya	10.5
[11]	Harare Shona (Zimbabwe)	9.8
[12]	Natal Zulu (S. Africa)	9.5
[9]	Luo (Kenya)	7.6
[9]	Mali Bandiagara	6.2
[7]	Sudanese	5.5
[9]	Kampala (Uganda)	5.2
[13]	Baka Pygmy (Cameroon)	5.0
[14]	Mestizos (Guadalajara,Mexico)	4.9
[15]	SEastern Isl (Cape Verde)	4.8
[16]	Nador Metalsa (Morocco)	4.8
[7]	Chiriguanos (Argentina)	4.7
[17]	Mossi (Burkina Faso)	4.7
[9]	Lusaka (Zambia)	4.7
[13]	Bamileke (Cameroon)	4.5
[7]	Sawa (Cameroon)	3.8
[7]	Kalash (Pakistan)	3.3
[7]	Beti (Cameroon)	3.2
[7]	SE France	3.1
[7]	Seri (Sonora,Mexico)	3.0
[7]	Yaounde (Cameroon)	2.8
[7]	Tunisia	2.5
[7]	Guinea Bissau	2.3
[7]	Fulani (Burkina Faso)	2.0
[7]	S. Portugal	2.0
[7]	Oman (E. Arabia)	1.7
[7]	Corsica (France)	1.6
[7]	Baloch (Pakistan)	1.6
[7]	Niokholo Mandenka (Senegal)	1.6
[7]	Eastern Andalusia (Spain)	1.5
[7]	Orkney (Scotland)	1.4
[7]	Mestizos (Mexico)	1.2
[7]	Baloch(Iran)	1.1
[7]	Bergamo (Italy)	1.1
[7]	Northern Han (China)	1.0
[7]	Central Portugal	1.0
[7]	Czech Republic	0.9
[7]	Northern Ireland	0.9
[7]	Jews (Israel)	0.9
[7]	Mixe (Oaxaca,Mexico)	0.9
[7]	Madeira (Spain)	0.8
[7]	Cayapa (Ecuador)	0.6
[7]	Svans (Georgia)	0.6
[7]	Majorca/Minorca (Spain)	0.6
[7]	Belgium	0.5
[7]	Lakota (Sioux)	0.5

A*6802

A*6802 has a global node within certain native peoples of South America, at 37%. A secondary node can be found in Africa. Like *6801 there is an hiatus of *6802 in SE Asia's indigenous populations, indicating that this population is not a likely source within the native peoples of the New World. Levels are generally low (<1%) in Europe except along the Mediterranean coast. In Africa, higher levels can be found in Kenya and in Western Africa and the Cape Verde Islands.[7] A note on purity, the notion that A*6802 is of indigeonous Native American origin can be challenged based on possibility of introgression from Europeans and Africans. In the case of the Yucpa this is not tenable. The Yucpa have an HLA-DQ8 frequency of ~80%, the highest DQ allele frequency in the world, this tribe shows little evidence of European genetic introgression, in addition the closest DQ8 frequency in terms of Africa are the isolated !Kung of Namibia. There are two possible sources of A*6802: Africa direct and Africa via Asia. The associated B alleles (B*48, B*61) point toward and Asian origin or an African source of very ancient origin, since time would be required to recombine Asian typical B alleles with A68. In the Spanish, A28 levels are 3.1% of this ~0.5% is A*6901, A*6802 is about 2.0% which means the net level of A*6802 to A*6805 in the Spanish is ~0.5%. Of 11 NA groups surveyed 9 are above and 2 are below 0.5%. Of the two Spanish groups 1 (Andalusia - 1.5%) is above and the other (Catalon 0.0%) is below. In an admixture model, Spanish introgression does not explain A*6802 in the New World. The Asian model of migration shows no single people NE of Pakistan that has A*6802.

A*6803

HLA A*6803 frequencies

		freq
ref.	Population	(%)
[18]	Mayan (Guatemala)	7.6
[19]	Bakalo pygmy (Cameroon)	6.0
[14]	Mestizo (Guadalajara, Mexico)	3.9
[20]	Mestizo (Mexico)	3.7
[19]	Mbenzele Pygmy (Central African)	1.5
[21]	Lakota (Sioux)	1.2
[22]	Yupik (Eskimo-Alaska)	1.0
[11]	Buriat (Mongolia)	0.4
[11]	N. Ireland, Romania, Czech,	0.0

A*6803 can be found in native peoples of the New World and in Central Asia, in Africa it appears to be limited to West and Central Africans. This distribution along with the information on 6801 and 6802 suggests a probable redistribution of *68 alleles from Africa after the initial migration from East Africa that colonized Southeast Asia. It also provides support for 2 waves of migration from Asia to the New World or, at minimum, an unknown mixing area of West Pacific Rim haplotypes and West African/Middle Eastern derived haplotypes in Eastern Asia before the first migration. At present the incursion of Western Eurasian peoples into East Asia follows evidence for reuse of transbiakal region after 18,300 years and correlates with the insipient Jōmon period of Japan several thousands of years later. Certain alleles and haplotypes of HLA in South Americans target Japan's estimated pre-Yayoi composition, but other peoples, for example in western Mexico are most similar to the Ainu and the peoples of the Amur basin.

A*6805

A*6805 is found in the Guatemalan and Central African Mbenzele at low levels.

A68 haplotypes

The genetic distance between Native Americans and Eurasians is too great for the persistence of shared haplotypes, particularly in light of the lower levels in most of Siberia. The link of haplotypes with Western Africa may be significant, and may indicate a rapid eastward migration and admixing within the late paleolithic period.

Indigeonous American haplotypes

A*680102-B35 haplotypes

• A*680102 Cw*0304 B*3506 (A68-Cw10-B35)
• A68-Cw4-B35 (Terena, Seri (Mexico))
  • A*680102 Cw*0401 B3521 (A68-Cw4-B35) (Terena)

A*6802-B35

• A*6802-B3501 Guadalahara
• A*6802-B3502 Guadalahara

A68-B35 Mayan (A*6803).

These two haplotypes are consistent with the presence of Cw4-B35 and A68 in Asia and Middle East and A68-B35 maybe the ancestral A68 haplotype. A28(A*6802)-B35 is found in Senegal.[23]

A6801-B4002/4 - Terena, Eskimo, Mestizo, Tribal Indians (Asia)

A*680102-B*520102 in the Mexican Mestizo population. A28(A*6802)-B52 is also found in Senegal.[23]

Old World A68 haplotypes

A28(~A68)-B51 Armenia, Senegal, Eskimo[23]
A28(~A68)-B70 W. Afr, Zaire, Zimbabwe, N. and S. African (Non-caucasians), Khoi (Hottentot)[23]

References

1. Arce-Gomez B, Jones EA, Barnstable CJ, Solomon E, Bodmer WF (February 1978). "The genetic control of HLA-A and B antigens in somatic cell hybrids: requirement for beta2 microglobulin". Tissue Antigens. 11 (2): 96–112. doi:10.1111/j.1399-0039.1978.tb01233.x. PMID 77067.
2. Allele Query Form IMGT/HLA - European Bioinformatics Institute
3. Tang J, Tang S, Lobashevsky E, Myracle A, Fideli U, Aldrovandi G, Allen S, Musonda R, Kaslow R (2002). "Favorable and Unfavorable HLA Class I Alleles and Haplotypes in Zambians Predominantly Infected with Clade C Human Immunodeficiency Virus Type 1". J Virol. 76 (16): 8276–84. doi:10.1128/JVI.76.16.8276-8284.2002. PMC 155130. PMID 12134033.
4. Gostick E, Cole DK, Hutchinson SL, et al. (2007). "Functional and biophysical characterization of an HLA-A*6801-restricted HIV-specific T cell receptor". Eur. J. Immunol. 37 (2): 479–86. doi:10.1002/eji.200636243. PMC 2699040. PMID 17273992.
5. Cruz-Robles D, Reyes PA, Monteón-Padilla VM, Ortiz-Muñiz AR, Vargas-Alarcón G (2004). "MHC class I and class II genes in Mexican patients with Chagas disease". Hum. Immunol. 65 (1): 60–5. doi:10.1016/j.humimm.2003.10.008. PMID 14700597.
6. Middleton D, Menchaca L, Rood H, Komerofsky R (2003). "New allele frequency database: http://www.allelefrequencies.net". Tissue Antigens. 61 (5): 403–7. doi:10.1034/j.1399-0039.2003.00062.x. PMID 12753660.
7. Middleton D, Menchaca L, Rood H, Komerofsky R (2003). "New allele frequency database: http://www.allelefrequencies.net". Tissue Antigens. 61 (5): 403–7. doi:10.1034/j.1399-0039.2003.00062.x. PMID 12753660. External link in |title= (help)
8. Layrisse Z, Guedez Y, Domínguez E, et al. (2001). "Extended HLA haplotypes in a Carib Amerindian population: the Yucpa of the Perija Range". Hum. Immunol. 62 (9): 992–1000. doi:10.1016/S0198-8859(01)00297-X. PMID 11543901.
9. Cao K, Moormann AM, Lyke KE, et al. (2004). "Differentiation between African populations is evidenced by the diversity of alleles and haplotypes of HLA class I loci". Tissue Antigens. 63 (4): 293–325. doi:10.1111/j.0001-2815.2004.00192.x. PMID 15009803.
10. Luo M, Embree J, Ramdahin S, et al. (2002). "HLA-A and HLA-B in Kenya, Africa: allele frequencies and identification of HLA-B*1567 and HLA-B*4426". Tissue Antigens. 59 (5): 370–80. doi:10.1034/j.1399-0039.2002.590503.x. PMID 12144620.
11. Proceedings of IHW Workshop, Seattle 2002, via http://www.allelefrequencies.net via Middleton D, Menchaca L, Rood H, Komerofsky R (2003). "New allele frequency database: http://www.allelefrequencies.net". Tissue Antigens. 61 (5): 403–7. doi:10.1034/j.1399-0039.2003.00062.x. PMID 12753660. External link in |title= (help)
12. Middleton D, Williams F, Meenagh A, et al. (2000). "Analysis of the distribution of HLA-A alleles in populations from five continents". Hum. Immunol. 61 (10): 1048–52. doi:10.1016/S0198-8859(00)00178-6. PMID 11082518.
13. Torimiro JN, Carr JK, Wolfe ND, et al. (2006). "HLA class I diversity among rural rainforest inhabitants in Cameroon: identification of A*2612-B*4407 haplotype". Tissue Antigens. 67 (1): 30–7. doi:10.1111/j.1399-0039.2005.00527.x. PMID 16451198.
14. Leal CA, Mendoza-Carrera F, Rivas F, Rodriguez-Reynoso S, Portilla-de Buen E (2005). "HLA-A and HLA-B allele frequencies in a mestizo population from Guadalajara, Mexico, determined by sequence-based typing". Tissue Antigens. 66 (6): 666–73. doi:10.1111/j.1399-0039.2005.00495.x. PMID 16305683.
15. Spínola H, Bruges-Armas J, Middleton D, Brehm A (2005). "HLA polymorphisms in Cabo Verde and Guiné-Bissau inferred from sequence-based typing". Hum. Immunol. 66 (10): 1082–92. doi:10.1016/j.humimm.2005.09.001. PMID 16386651.
16. Oumhani K, Canossi A, Piancatelli D, et al. (2002). "Sequence-Based analysis of the HLA-DRB1 polymorphism in Metalsa Berber and Chaouya Arabic-speaking groups from Morocco". Hum. Immunol. 63 (2): 129–38. doi:10.1016/S0198-8859(01)00370-6. PMID 11821160.
17. Modiano D, Luoni G, Petrarca V, et al. (2001). "HLA class I in three West African ethnic groups: genetic distances from sub-Saharan and Caucasoid populations". Tissue Antigens. 57 (2): 128–37. doi:10.1034/j.1399-0039.2001.057002128.x. PMID 11260507.
18. Gómez-Casado E, Martínez-Laso J, Moscoso J, et al. (2003). "Origin of Mayans according to HLA genes and the uniqueness of Amerindians". Tissue Antigens. 61 (6): 425–36. doi:10.1034/j.1399-0039.2003.00040.x. PMID 12823766.
19. Bruges Armas J, Destro-Bisol G, López-Vazquez A, et al. (2003). "HLA class I variation in the West African Pygmies and their genetic relationship with other African populations". Tissue Antigens. 62 (3): 233–42. doi:10.1034/j.1399-0039.2003.00100.x. PMID 12956877.
20. Williams F, Meenagh A, Darke C, et al. (2001). "Analysis of the distribution of HLA-B alleles in populations from five continents". Hum. Immunol. 62 (6): 645–50. doi:10.1016/S0198-8859(01)00247-6. PMID 11390040.
21. Leffell MS, Fallin MD, Hildebrand WH, Cavett JW, Iglehart BA, Zachary AA (2004). "HLA alleles and haplotypes among the Lakota Sioux: report of the ASHI minority workshops, part III". Hum. Immunol. 65 (1): 78–89. doi:10.1016/j.humimm.2003.10.001. PMID 14700599.
22. Leffell MS, Fallin MD, Erlich HA, et al. (2002). "HLA antigens, alleles and haplotypes among the Yup'ik Alaska natives: report of the ASHI Minority Workshops, Part II". Hum. Immunol. 63 (7): 614–25. doi:10.1016/S0198-8859(02)00415-9. PMID 12072196.
23. [Note: Since freq(A28) = freq(A68) + freq(A69) and A69 is not widely distributed in Africa (mainly levant, cape verde islands, certain tribes in Burkino Faso), A28 frequencies can generally be treated as A68 frequencies]