Indian Journal of Human Genetics Medknow Publications on behalf of Indian Society of Human Genetics ISSN: 0971-6866 EISSN: 1998-362x Vol. 9, Num. 1, 2003, pp. 13-16

Indian Journal of Human Genetics, Vol. 9, No. 1, Jan-Jun, 2003, pp. 13-16

HLA A19 subtypes and B loci related haplotype in selected caste groups from the Indian population

U. Shankarkumar

HLA Department, Institute of Immunohaematology (ICMR), 13th Floor, NMS Building, K.E.M.Hospital Campus, Parel, Mumbai-400012, Maharastra, India.
Address for correspondence: U. Shankarkumar, HLA Department, Institute of Immunohaematology (ICMR), 13th Floor, NMS Building, K.E.M. Hospital Campus, Parel, Mumbai-400012, Maharastra, India. E-mail: Shankarkumar16@hotmail.com

Code Number: hg03004

The Indian population has been broadly classified as Aryans of Northern India and Dravidians of South India. The present study was undertaken to compile available data and investigate the genetic diversity of HLA A19 subtypes in Indians and its associated B locus haplotype frequency distribution at the population level. The study revealed that A33 was common among the selected North Indian caste groups (Aryans) while A31 was common among the selected South Indian caste groups (Dravidians). The haplotypes A33-B44 and A19-B35 were characteristic to Aryans while haplotypes A19-B22 and A19-B7 were characteristic to Dravidians. Further novel haplotypes such as A19-B14 and A33-B49 were unique to Parsis and Sourastran caste. A low frequency of A29 was observed among the A19 subtype repertoire. Prevalence of HLA A33 and A31 among North Indians (Aryans) and South Indians (Dravidians) along with their unique haplotypes may be a consequence of the founder effect, racial admixture or selection pressure due to environmental factors among this population.

Key Words: HLA A19, Caste groups, Founder effect, Selection, India.

INTRODUCTION

The HLA Aw19 subtype complex viz: A29, A30, A31, A32, A33, and A74 were serologically described in the series of 4^th to 8^th International Histocompatibility Workshop.¹ World over HLA A19 serological subtypes occur with varying frequencies in different populations. A29 subtype occurs in Basque (11.3%), A30 subtype occurs in Bhusman (20.4%), in Sardinian (22.3%), in Asians (0.72%), in Caucasians (0.6%), and in Blacks with a high frequency (9.3 - 31.6%).² A31 subtype occurs in South American Black (5.4%), and Japanese (8%), A32 occur in Greeks (9%) and A33 occur with a high frequency among West African (15.2%) and Iyers (17.5%).³ However the distribution of A19 subtypes in Indian population is scarcely reported.^4-9 It is believed that the majority of the sequence polymorphism amongst HLA Class I alleles lie within the exon 2 and exon 3.¹⁰ The present study focuses on the distribution of A19 subtypes and its B associated haplotypes in Indian population.

MATERIAL AND METHODS

To determine the frequency of the different A19 subtypes and associated B loci haplotypes, a total of 1396 individuals from India were compiled from published literature for A19 subtypes that was determined by serology.^4-9 Further, 176 individuals consisting of a Maratha (Aryan caste = 65), a Nadar (Dravidian caste = 61) and Immigrant population (Parsis = 50) were also studied. The individuals tested in this study are not blood relatives to the best of my knowledge. Ten to fifteen milliliters of venous blood (in heparin 50 IU/ml) was collected in a sterile tube from each individual. The lymphocytes were isolated by density gradient centrifugation on Histopaque. NIH two - stage microlymphocytotoxicity assay,¹¹ identified HLA antigens. The antisera were commercial (Biotest, Germany; Behring, Germany; Pelfreez, USA) and indigenous¹² in origin. The typing tray included a minimum of three antisera for each supertypic specificity. The allele frequency (AF) and percentage haplotype frequency (HF) was calculated following the method described earlier.¹³

RESULTS

Some significant findings can be concluded from this study. (1) HLA A31 was the most frequent subtype among selected caste groups of South India (Dravidians) while A33 was the frequent subtype among the selected caste groups of North India (Aryans) (Table 1). (2) Further, HLA haplotypes A19-B35, A33-B44 was common among the Aryans of North India while A19-B7 and A19-B22 was common among the Dravidians of South India (Table 2). (3) Further it was observed that A19-B7 was also present among highly conserved Vatalia prajapathis of North India, while A33-B44 was observed among the Iyer caste groups of South India indicating that considerable admixture has been occurred over the North and South Indian population. (4) Some of the haplotypes such as A19-B14 and A33- B49 were unique to Parsis and Sourastrans indicating that they are isolated population or caste groups with out admixture.

DISCUSSION

The distribution of A19 subtype alleles in the Indian population shows high levels of gene diversity. The gene pool in the Indian subcontinent can best be described as " a melting pot of races," having experienced several foreign invasions from the east as well as the west. The data compiled and presented in this study presents a clear picture of the inherent diversity in A*19 subtype family of alleles among the Indians. HLA Diversity within population groups is generated owing to the founder effect, selection or random genetic drift, intergeneic recombination, and/or population admixture.¹⁴ Analysis on genetic variations on Golla pastoral caste subdivisions of Andhra Pradesh recently, indicate that, the subcastes exhibit a high haplotype variability and their genetic substratum may be the result of European - Middle East/ Asian admixture with the autochthonous population.¹⁵ In a study, among diverse geographically distributed Brazilian, Colombian, Cuban, Mexican, Omani, Singapore Chinese and South African Zulu populations for HLA A locus allelic diversity showed that A*74 was detected in six of the populations.¹⁶ Recently, increased A33 subtypes such as A*3303^17,18 and novel alleles like A*3306¹⁹ have been reported from India. Haplotypes A*3303-B*44032 (18.3%), A*3001-B*1302 (9.7%), A*3101-B*51 (8.5%), A*3101-B*5201 (3.6%), A*3303-B*5801 (8.5%), A*32-B*35 (4.8%), A*33-B*35 (4.8%) has been reported from North India where as only four haplotypes of these were encountered in Japanese.¹⁸ Further, HLA A19 has also been implicated in a number of diseases such as Carcinoma of liver, Renal Cell Carcinoma, Kaposi's sarcoma, Mycosis Fungoides,²⁰ Vitiligo,²¹ Rheumatic Heart disease,²² Ulcerative Colitis,²³ and antibodies to A19 and B35 complexes were recorded in 86% of infertile men and 92% of infertile women.²⁴

The history of Indian subcontinent documents a series of invasions from raiders and accounts of a large number of travelers and scholars from the East. The Indian population can be broadly classified into Dravidians and Aryans. The Dravidians are considered to be the original inhabitants that were driven southwards by frequent invasions from east and West of the country. The North Indians are the descendents of the Aryans who migrated from Iranian plateau and exhibit a mixed gene pool as evident in this study and previous HLA studies. The extensive admixture from white, Oriental and black races in the Indian population is also evident from the recent reports on the molecular diversity of HLA A2,^25,26,31 A19,¹⁷ B27,²⁷ DR4²⁸ and novel disease associated alleles B*27²⁹ and DRB1*1508.³⁰ It is highly warranted that study from most of the indigenous population caste groups and tribal groups are important to determine the presence of unique alleles in genetically diverse Indian population. These HLA data when generated will be useful in reconstruction of population history and evolutionary affinities thereby giving the best opportunity to identify the unrelated bone marrow donor within the population group for BMT and as well in identifying the disease association mechanisms involving HLA A19 subtypes in India.

REFERENCES

1. Dick M. HLA A, B and C serology and antigen reports. In: Bodmer WF, editor. Histocompatibility Testing 1977. Munksgaard.Copenhagen; 1977. pp. 157.
2. Lee KW, Tang TF, Yang SY. HLA A*30 alleles and associated haplotypes in Korean population. Tissue Antigens 1999;54:198-.
3. Imanishi T, Akaza T, Kimura A, Tokunaga K, Gojorbi T. Allele and haplotype frequencies for HLA and complement loci in various ethnic groups. In: Tusji K, Aizawa M, Sasazuki T, editor. HLA 1991. Vol 1. Oxford: Oxford University press; 1992. pp. 1065.
4. Rajasekar R, Kakkaniah VN, Pitchappan RM. HLA antigens in South India: II selected caste groups of Tamil Nadu. Tissue Antigens 1987;30:113-8.
5. Balakrishnan K, Pitchappan RM, Suzuki K, Shankarkumar U, Shanthakumari R, Tokunaga K. HLA affinities of Iyers, a Brahmin population of Tamil Nadu. South India. Hum Biol 1996;64:523-37.
6. Shankarkumar U, Ghosh K, Mohanty D. HLA class I antigen profile among Brahmins and related caste groups from Mumbai. Maharastra, India. Ind J Hum Genet 2000;6:21-8.
7. Shankarkumar U, Ghosh K, Mohanty D. HLA antigen distribution in Maratha community from Mumbai. Maharastra, India. Int J Hum Genet 2001;1:173-7.
8. Chayya SU, Shankarkumar U. HLA antigen distribution in Jain community from Mumbai, Maharastra, India. Ind J Med Res 2001;114:25-9.
9. Shankarkumar U, Ghosh K, Colah RB, Gorakshakar AC, Gupte SC, Mohanty D. HLA antigen distribution in selected caste groups from Mumbai, Maharastra, India J Hum Ecol 2002;13:209-15.
10. Mason PM, Parham P. HLA class I region sequences 1998. Tissue Antigens 1998;51:417.
11. Terasaki PI, Mc Clelland JD. Microdroplet assay for human cytotoxins. Nature 1964;204:998-1000.
12. Shankarkumar U, Gupte SC, Gupte SS, Pednakar SV, Ghosh K, Mohanty D. Frequency and potential applicationof HLA antibodies from pregnant women in Mumbai. J Bio Sci 1998;23:601-4.
13. Shankarkumar U, Devaraj JP, Ghosh K, Mohanty D. Seronegative spondarthritis (SSA) and human leukocyte antigen association. Br J Bio Med Sci 2002;59:38-41.
14. Awdeh ZL, Raum D, Yunis EJ, Alper CA. Extended HLA/complement allele haplotypes: evidence for T/t like complex in man. Proc Natl Acd Sci USA 1983;80:259.
15. Crawford MH, Mohan Reddy B, Jorge ML, Mack SJ, Erlich HA. Genetic variation among the Golla Pastoral caste subdivisions of Andhra Pradesh, India, According to the HLA system. Hum Immunol 2001;62:1031.
16. Middleton D, Williams F, Meenagh A, Daar AS, Gorodezky C, Hammond M, et al. Analysis of the distribution of HLA A alleles in populations from five Continents. Hum Immunol 2000;61:1048.
17. Shankarkumar U, Ghosh K, Mohanty D. Defining the alleleic variants of HLA A19 in the western Indian population. Hum Immunol 2002;63:779-82.
18. Jaini R, Naruse T, Kanga U, Kikkawa E, Kaur G, Inoko H, Menra NK. Molecular diversity of the HLA A19 group of alleles in North Indians: possible Oriental influence. Tissue Antigens 2002;59:487-91.
19. Rozemuller EH, Mehra NK, Van der Zwan A, Jaini R, Tilanus MGJ. HLA A*3306: a novel HLA A variant in the Indian population. Tissue Antigens 2002;59:
20. Tiwari T, Terasaki PI. HLA and Disease associations Springer verlag. New York: 1995. pp. 32.
21. Al-Fouzan A, al-Arbash M, Fouad F, Kaaba SA, Mousa MA, al-Harbi SA: Study of HLA class I/II and T lymphocyte subsets in Kuwaiti Vitiligo patients. Eur J Immunogent 1995;22:209.
22. Wani BA. Study of HLA A, B, C, DR, DQ profile of patients with established Rheumatic heart disease in Khasmir. Ind.Heart J 1997;49:152.
23. Habeeb MA, Rajalingam R, Dhar A, Kumar A, Sharma MP, Mehra NK. HLA association and occurrence of autoantibodies in Asian Indian patients with ulcerative colitis. Am J Gasteroentrol 1997;92:733.
24. Genco PV, Mathur S, Williamson HO, Rust PF, Glassman AB, Fudenberg HH. Antibodies to A19 and Bw35 complexes of human leukocyte antigens are present in infertile subjects with sperm antibodies. Fertil Steril 1984;42:554.
25. Shankarkumar U, Devaraj JP, Ghosh K, Mohanty D. HLA A*02 allele frequencies and B haplotype associations in Western India. Hum Immuol.2003;64:562-6.
26. Mehra NK, Jaini R, Rajalingam R, Balamurugan A, Kaur G. Molecular diversity of HLA A*02 in Asian Indians: predominance of A*0211. Tissue Antigens 2001; 57:502.
27. Shankarkumar U, Ghosh K, Mohanty D. HLA B27 diversity from Western India. Tissue Antigens 2002;60:98-101.
28. Jaini R, Kaur G, Mehra NK. Heterogeneity of HLA DR*04 and its associated haplotypes in the North Indian population. Hum Immunol 2001;63:25-9.
29. Ghosh K, Shankarkumar U, Shetty S, Mohanty D. Chronic synovitis and HLA B27 in patients with severe haemophilia. Lancet 2003;361:933-4.
30. Kankonkar S, Jeyanthi G, Singhal BS, Shankarkumar U. Evidence for novel DRB1*15 allele associations among clinically definite Multiple sclerosis patients from Mumbai. Hum Immunol 2003;64:478-82.
31. Shankarkumar U. HLA A*02 allele and B associated haplotype diversity in Indians. Br J Biomed. Sci 2003;60:109-12.

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