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  Table of Contents    
BRIEF COMMUNICATION  
Year : 2016  |  Volume : 59  |  Issue : 1  |  Page : 59-62
Genetic diversity through human leukocyte antigen typing in end-stage renal disease patients and prospective donors of North India


Department of Transfusion Medicine, Transplant Immunology and Molecular Biology, Indraprastha Apollo Hospitals, New Delhi, India

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Date of Web Publication9-Mar-2016
 

   Abstract 

As the incidence of end-stage renal disease (ESRD) is rapidly increasing, the demand for dialysis and transplantation has dramatically increased, which has led to concerns about the availability and equitable allocation of kidneys for transplantation. The distribution of HLA-A, B and DR alleles in 148 renal transplant recipients and 191 live related prospective donors from 2009 to 2010 were analyzed. Allele frequencies and haplotype frequencies were calculated in recipients and donors. The prospective donors were further analyzed on the basis of their relationship to the patients and according to the sex ratio. A significant female preponderance was noted in the prospective donor population, most of whom were either siblings or parents of the recipients. On the contrary, the recipient population predominantly comprised of males. The most frequent HLA-A, HLA-B, HLA-DRB1 alleles in renal transplant patients were HLA-A*11, A*02, A*01, A*24; HLA-B*35, B*40, B*44, B*15, B*52, and HLA-DRB1*15, DRB1*07, DRB1*13, DRB1*11 respectively. The most frequent HLA-A, HLA-B, HLA-DRB1 alleles in prospective donors were HLA-A*02, A*11, A*33, A*24; HLA-B*35, B*44, B*40, B*15 and HLA-DRB1*15, DRB1*07, DRB1*11, DRB1*13 respectively. A*11-B*35, A*02-DRB1*15, B*40-DRB1*15 were the most common HLA A-B , HLA A-DR, HLA B-DR haplotypes respectively in renal transplant patients, whereas, A*11-B*35, A*11-DRB1*15, B*44-DRB1*07 were the most common haplotypes in renal donors. In three locus haplotype, HLA-A*02-B*40-DRB1*15 was the most frequent haplotype in patients, whereas, in prospective renal donors HLA-A*33-B*44-DRB1*07 was the most frequent haplotype.

Keywords: Allele frequency, end-stage renal disease, haplotype frequency

How to cite this article:
Chowdhry M, Makroo RN, Kumar M. Genetic diversity through human leukocyte antigen typing in end-stage renal disease patients and prospective donors of North India . Indian J Pathol Microbiol 2016;59:59-62

How to cite this URL:
Chowdhry M, Makroo RN, Kumar M. Genetic diversity through human leukocyte antigen typing in end-stage renal disease patients and prospective donors of North India . Indian J Pathol Microbiol [serial online] 2016 [cited 2019 Aug 17];59:59-62. Available from: http://www.ijpmonline.org/text.asp?2016/59/1/59/178221



   Introduction Top


The incidence of end-stage renal disease has increased dramatically in the past decade. [1] Generally, renal transplantation is a treatment that is preferred by patients with chronic renal failure. [2] When compared to dialysis, transplantation allows the patient to lead a long and healthy life with a decrease in healthcare expenses. [1] Generally, the success of renal transplantation depends on the human leukocyte antigen (HLA) compatibility between recipients and donors. [2] The HLA Class I and II genes represent the most polymorphic set of genes in the human genome. [3] HLA antigens are inherited in a co-dominant manner from parents to the offsprings'. In the live related transplants, there is only 25% chance that two siblings would be 100% identical, 50% chance that they will share one haplotype, and 25% that they will not share any of the haplotype. [4]


   Materials and methods Top


A total of 148 renal transplant recipients and 191 live related prospective donors referred to the Department of Molecular Biology and Transplant Immunology for HLA typing from 2009 to 2010 were included. An informed consent of the individuals participating in the study was obtained. Allele frequencies were estimated using the PowerStat version 1.2 (Promega Corporation, USA). Haplotype frequencies were calculated from genotype data by expectation maximization algorithm using Arlequin software package version 3.0. [5] Molecular HLA typing was done by sequence specific primer.


   Results Top


Among the prospective donors, 31.9% were related as siblings, 42.4% were parents, 9.4% were offspring, 2.6% were spousal donors, and 8.3% were other donors such as cousins or uncles. Most of the prospective donors were females (58.6%) (P < 0.05), while most of the patients were males (81.8%) (P < 0.05). The most frequent HLA-A, HLA-B, HLA-DRB1 alleles in renal transplant patients were HLA-A*11 (17.6%), A*02 (15.6%), A*01 (13.7%), A*24 (12.5%); HLA-B*35 (12.0%), B*40 (11.7%), B*44 (8.3%), B*15 (7.9%); and HLA-DRB1*15 (19.6%), DRB1*07 (13.0%), DRB1*13 (11.7%), DRB1*11 (10.9%), respectively. The most frequent HLA-A, HLA-B, HLA-DRB1 alleles in prospective donors were HLA-A*02 (17.5%), A*11 (14.3%), A*33 (12.0%), A*24 (12.0%); HLA-B*35 (12.0%), B*44 (11.0%), B*40 (10.4%), B*15 (8.9%); and HLA-DRB1*15 (19.3%), DRB1*07 (17.2%), DRB1*11 (10.3%), DRB1*13 (9.3%), respectively [Table 1]. HLA-A*11-B*35 (10.13%) was the most common HLA-A-B haplotype in both renal transplant patients and prospective donors [Table 2]. HLA-A*02-DRB1*15 (12.83%) was the most common HLA-A-B haplotype in renal transplant patients whereas A*11-DRB1*15 (12.5%) was the most common haplotype in prospective donors [Table 2]. HLA-A*02-DRB1*15 (12.83%) was the most common HLA-A-DRB1 haplotype in renal transplant patients whereas A*11-DRB1*15 (12.5%) was the most common haplotype in prospective donors [Table 2]. HLA-B*40-DRB1*15 (14.18%), was the most common HLA-B-DRB1 haplotype in renal transplant patients whereas B*44-DRB1*07 (16.23%) was the most common haplotype in prospective donors [Table 2].
Table 1: Allele frequency of HLA-A, HLA-B and HLA-DR in donor and patient population


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Table 2: Haplotype frequency of HLA-A-B, HLA-A-DR and HLA-B-DR in donor and patient population


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At three locus haplotype (HLA-A-B-DR) in renal transplant patient, HLA-A*02-B*40-DRB1*15 (6.08%) was the most frequent three haplotype followed by HLA-A*11-B*52-DRB1*07 (3.37%), HLA-A*33-B*44-DRB1*07 (3.37%), HLA-A*01-B*40-DRB1*15 (2.7%), HLA-A*24-B*44-DRB1*07 (2.7%), and HLA-A*11-B*15-DRB1*15 (2.7%). At three locus haplotype (HLA-A-B-DR) in prospective renal transplant donors, HLA-A*33-B*44-DRB1*07 (8.9%) was the most frequent three locus haplotype followed by HLA-A*02-B*44-DRB1*07 (7.85%), HLA-A*02-B*40-DRB1*15 (4.71%), and HLA-A*24-B*44-DRB1*07 (4.71%) [Table 3].
Table 3: Haplotype frequency of HLA-A-B-DR in donor and patient population


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   Discussion Top


Among the prospective renal donors, most of them were blood relatives of the patient as cadaveric renal transplant program is still in its initial phases in India. Cadaver donation has not become very popular in India. [6] Among the relatives, most of the prospective donors were females. This is similar to other studies done in the recent past. [6],[7] This could be mainly because of the social structure and taboos present in the Indian subcontinent where females are most of the time compelled either emotionally or morally to become a prospective donor.

In the present study, we have tried to compare the allele frequency of HLA-A, HLA-B, HLA-DRB1 with the other populations of India namely, Uttar Pradesh, [4] North Indians of Delhi, [8] and South Indians. [9]

Our results show that allele frequency of HLA-A, B, and DR antigens do not differ from one another. However, a few alleles were found to be either increased or decreased as compared to other population In HLA-A alleles, HLA-A*33 (12%) was significantly raised in our study, compared to other studies such as in North Indians of Delhi [8] (4%), Uttar Pradesh [4] (4.36%), and South Indians [9] (0%). Similarly, HLA-A*24, which was present at a high frequency in our population and Uttar Pradesh population, was found to be completely absent in the study done by Mehra et al. [7] in the North Indian Hindu population.

In HLA-B alleles, most of our results corroborated with other studies which we have compared earlier. [4],[8],[9] However, in HLA-DRB1, interestingly, in our study and the study done by Agarwal et al. [4] in Uttar Pradesh, HLA-DRB1*15, DRB1*11, and DRB1*13 were alleles occurring in a high frequency. However, this is not the case in the study done by Mehra et al. [8] where these alleles were completely absent.

HLA haplotype is a powerful marker and is useful for surveys among closely related ethnic groups. [10] We have also analyzed and compared the two locus and three locus haplotypes between the renal transplants patients and prospective donors in our study. The two locus haplotypes revealed that there is no significant difference between the patients and donors. In three locus haplotypes, the most common haplotype was A*02-B*40-DRB1*15, both in patients (6.08%) and donors (4.71%). This has been proven time and again in various earlier studies. [11] However, in three locus haplotypes, we also found that the haplotypes A*02-B*44-DRB1*07 and A*33-B*44-DRB1*07 were significantly raised in the donor population compared to renal transplant patients P < 0.05. This haplotypes being much more in donor population than the patient population suggests that it may have a protective influence on the kidney.

Our data suggests that, between the patients and donor, there is not much genetic diversity as they come from the same race. Since, the data included in the study is not sufficiently large, it is not possible to ascertain all the haplotypes that may occur in the population. We, in our study, have also detected alleles which are not indigenous to this region. These findings reinforce that some of the rare haplotypes may have been missed. Furthermore, some haplotypes with low frequency may actually not be represented in this population. Ironically, some of the alleles which were not thought to be occurring in this region (as shown in previous studies) have been ascertained in our study.

To our knowledge, the data presented in this study for the HLA allele and haplotype frequencies of Indian population is an extensive report for both renal transplant recipients and donors of the country with special emphases on the social aspect of organ donation including gender bias. The fact that few haplotypes are represented significantly in the donor population than in the patient population should be an area of research for us, to verify if they have a protective influence on the kidney related diseases or it's just a chance occurrence.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Stolzmann KL, Bautista LE, Gangnon RE, McElroy JA, Becker BN, Remington PL. Trends in kidney transplantation rates and disparities. J Natl Med Assoc 2007;99:923-32.  Back to cited text no. 1
    
2.
Prasanavar D, Shankarkumar U. HLA gene and haplotype frequency in renal transplant recipients and donors of Maharashtra (Western India). Int J Hum Genet 2004;4:155-9.  Back to cited text no. 2
    
3.
Listgarten J, Brumme Z, Kadie C, Xiaojiang G, Walker B, Carrington M, et al. Statistical resolution of ambiguous HLA typing data. PLoS Comput Biol 2008;4:e1000016.  Back to cited text no. 3
    
4.
Agarwal S, Singh AK, Sharma RK. HLA gene and haplotype frequency in renal transplant recipients and donors of Utter Pradesh (North India). Indian J Nephrol 2001;11:88-97.  Back to cited text no. 4
    
5.
Excoffier, LG Laval, S Schneider. Arlequin ver. 3.0: An integrated software package for population genetics data analysis. Evolutionary Bioinformatics Online 2005;1:47-50.  Back to cited text no. 5
    
6.
Mishra MN, Saxena VK, Narula AS. Differences in renal transplantation in India and first world countries. Int J Hum Genet 2004;4:161-5.  Back to cited text no. 6
    
7.
Panigrahi A, Agarwal SK, Kanga U, Guleria S, Bhowmik D, Dash SC, et al. Influence of HLA compatibility on renal graft survival using live unrelated & cadaver donors in India. Indian J Med Res 2002;115:158-64.  Back to cited text no. 7
    
8.
Mehra NK, Taneja V, Kailash S, Raizada N, Vaidya MC; Distribution of HLA antigen in samples of North Indian Hindu population. Tissue Antigen 1986;27:64-74.  Back to cited text no. 8
    
9.
Pitchappan RM, Kakkanaiah VN, Rajshekhar R, Arulraj N, Muttukkaruppan VR. HLA antigens in south India: I Major group of Tamil Nadu. Tissue Antigen 1984;24:1906.  Back to cited text no. 9
    
10.
Leffell MS, Steinberg AG, Bias WB, Machan CH, Zachary AA. The distribution of HLA antigens and phenotypes among donors and patients in the UNOS registry. Transplantation 1994;58:1119-30.  Back to cited text no. 10
    
11.
Shankarkumar U. Complexities and similarities of HLA antigen distribution in Asian subcontinent. Indian J Hum Genet 2010;16:108-10.  Back to cited text no. 11
[PUBMED]  Medknow Journal  

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Correspondence Address:
Mohit Chowdhry
Department of Transfusion Medicine, Transplant Immunology and Molecular Biology, Indraprastha Apollo Hospitals, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.178221

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