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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
RENAL DATA FROM ASIA-AFRICA  
Year : 2011  |  Volume : 22  |  Issue : 4  |  Page : 834-840
HLA polymorphism in Sudanese renal donors


1 Department of Molecular Biology, Institute of Nuclear Medicine, Molecular Biology and Oncology (INMO), University of Gezira, Sudan
2 Department of Immunology, University of London, United Kingdom
3 Department of Surgery, Faculty of Medicine, University of Gezira, Sudan
4 Department of Pathology, Faculty of Medicine, University of Gezira, Sudan

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Date of Web Publication9-Jul-2011
 

   Abstract 

The main objective of this study is to provide a database for renal transplantation in Sudan and to determine the HLA antigens and haplotype frequencies (HFs) in the study subjects. HLA typing was performed using the complement-dependant lymphocytotoxicity test in 250 unrelated healthy individuals selected as donors in the Sudanese Renal Transplantation Program. Considerable polymorphism was observed at each locus; A2 (0.28), A30 (0.12), A3 (0.09), A24 (0.09), A1 (0.09), and A68 (0.06) were the most frequent antigens in the A locus, while B51 (0.092), B41 (0.081), B39 (0.078), B57 (0.060), B35 (0.068), B 50 (0.053) and B 52 (0.051) were the most common B locus antigens. DR13 (0.444) and DR15 (0.160) showed the highest antigen frequencies (AFs) in the DR locus. In the DQ locus, DQ1 showed the highest gene frequency (0.498), while DQ2 and DQ3 AFs were (0.185) and (0.238), respectively. The most common HLA-A and -B haplotypes in positive linkage disequilibrium were A24, B38; A1, B7; and A3, B52. The common HLA-A and -B HFs in positive linkage disequilibrium in the main three tribe-stocks of the study subjects (Gaalia, Nile Nubian and Johyna) were A24, B38 for Gaalia; A24, B38 and A2, B7 for Johyna; and A2, B64 and A3, B53 for Nile Nubian. These results suggest that both class I and class II polymorphisms of the study subjects depict considerable heterogeneity, which reflects recent admixture of this group with neighboring Arabs and African populations.

How to cite this article:
Dafalla AM, McCloskey D J, Alemam AA, Ibrahim AA, Babikir AM, Gasmelseed N, El Imam M, Mohamedani AA, Magzoub MM. HLA polymorphism in Sudanese renal donors. Saudi J Kidney Dis Transpl 2011;22:834-40

How to cite this URL:
Dafalla AM, McCloskey D J, Alemam AA, Ibrahim AA, Babikir AM, Gasmelseed N, El Imam M, Mohamedani AA, Magzoub MM. HLA polymorphism in Sudanese renal donors. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2017 Nov 24];22:834-40. Available from: http://www.sjkdt.org/text.asp?2011/22/4/834/82738

   Introduction Top


The human leukocyte antigen (HLA) system is one of the most polymorphic genetic system and is broadly divided into class I (HLA-A, HLA-B, and HLA-C) and class II (HLA-DP, HLA-DQ and HLA-DR) loci, which are subdivided into distinct regions. Polymorphism in the HLA system was used as a tool for anthropological studies, as genetic distances and correspondence analysis demonstrated that the allele and haplotype distribution of class I and class II loci are racially and geographically restricted. [1] This prompted the use of HLA class I and class II phenotype and haplotypes in different ethnic groups for the analysis of the origin, migration and the degree of admixture of populations. [2] Sudan is located in heart of Africa and surrounded by eight countries of different ethnic origins. HLA gene and haplotype frequencies (HFs) have been described in different racial groups. [3] A few studies have also emerged from Sudan region, which report HLA antigen frequencies (AFs). [4]


   Objective Top


The main objective of this study is to provide a database for renal transplantation in Sudan and to determine the HLA AFs and HFs in the study subjects.


   Patients and Methods Top


Blood samples were collected after a written consent was obtained from 250 (185 males, 65 females) unrelated healthy Sudanese individuals in the Sudanese Renal Transplantation Program in Gezira Hospital for Renal Diseases and Transplantation and Ahmed Gasim Hospital in Khartoum, in addition to randomly selected donors planned for operations in private centers outside Sudan. Those healthy volunteers were categorized into three ethnic groups based on the official documents and family history as follows: Gaalia (48.4%), Nile Nubian (16.6%), and Johyna tribes (14.4%).

HLA typing was conducted by using the standard microlymphocytotoxicity test using commercially available reagents from One Lambda Inc. (CA, USA). In brief, whole blood sample (10 mL) was collected in acid citrate dextrose (ACD) tubes and T and B lymphocytes were separated by T-and B-immunomagnetic beads (Dynal, Oslo, Norway/One Lambda Inc., CA, USA) and incubated with HLA-specific class I and class II antisera, respectively. This was followed by incubation with rabbit complement, and then ethidium bromide/acridine orange stain was added. The reactions were scored using a fluorescent microscope that estimates the percentage of cell death according to the American Society of Histocompatiblity and Immunogenetics (ASHI) Standard Readings.


   Statistical Analysis Top


Gene frequencies (GFs) were estimated; comparison between frequencies observed in different ethnic groups was tested using Chi-square analysis. Linkage disequilibrium (LD) was measured by D coefficient defined by Lewontin. [5] GF (g) was calculated from the AF (f) using the formula: g = 1 -√(1-f). [6] The P value was considered as significant when it was <0.05.


   Results Top


Ethnic groups of the study samples

The study samples were of different ethnic groups of the Sudanese population. 48.4% of them were Gaalia stock, 16.6% were Nile Nubian, 14.4% were Johyna stock and 8.8%, 3.6%, 3.2%, 2.0%, 2.0%, and 0.4% were Baggara, Egyptian stock, Nubians, Nigerian stock, Nilotican stock and Beja, respectively.

HLA -A, -B, -DR and -DQ serological tissue typing results

Considerable polymorphism was observed at each locus; at the A locus, 19 different antigens out of 27 known antigens were observed. A2, A30, A3, A24, A1 and A68 were the most frequent antigens with GFs 0.282, 0.117, 0.092, 0.090, 0.088, and 0.060, respectively. The AFs and GFs are shown in [Table 1].
Table 1: Frequencies of class I antigens (A and B loci) of the study subjects (n = 250).

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Analysis of antigenic variation among the three different ethnic groups showed that A2 and A30 were the commonest HLA-A antigens among Gaalia and Nile Nubians stocks [Table 2].
Table 2: Frequencies of HLA-A locus antigens of Gaalia, Nile Nubian and Johyna stocks.

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At the HLA-B locus, the predominant antigens observed in Sudanese population were B51 (0.092), B41 (0.081), B39 (0.078), B35 (0.068), B57 (0.060), B50 (0.053) and B52 (0.051). Antigenic comparison among ethnic groups showed that B51 was high in Johyna stock (0.134) and B41 in Nile Nubians (0.155). B35 was observed only in (0.001) Gaalia stock [Table 3].
Table 3: Frequencies of HLA-B locus antigens of Gaalia, Nile Nubian and Johyna stocks.

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As shown in [Table 4], all the HLA-DR known antigens have been detected in the Sudanese population and their GFs were DR13 (0.254), DR15 (0.160), DR11 (0.135), DR8 (0.088), DR7 (0.086) and DR17 (0.064).
Table 4: Frequencies of class II antigens (DR and DQ loci) of the study subjects.

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DR13, DR15 and DR11 were the most frequent specificities in the three main tribe-stocks in the study subjects; their GFs in Gaalia were (0.261), (0.162) and (0.133), respectively, in Nile Nubian were (0.293), (0.213) and (0.127), respectively, and in Johyna were (0.236), (0.167) and (0.118), respectively [Table 5].
Table 5: Frequencies of HLA-DR and -DQ loci antigens of Gaalia, Nile Nubian and Johyna stocks.

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Concerning HLA-DQ polymorphisms, DQ1 showed the highest GF (0.498), while DQ3 and DQ2 AFs were (0.238) and (0.185), respectively [Table 4]. In the DQ locus, DQ1, DQ3 and DQ2 were the most frequent specificities in the three main tribe-stocks of the study subjects; their GFs in Gaalia were (0.470), (0.234) and (0.202), respectively, in Nile Nubian were (0.564), (0.184) and (0.184), respectively, and in Johyna were (0.592), (0.236) and (0.167), respectively [Table 5].

The most common HLA-A and -B haplotypes in positive LD in the studied subjects were A24, B38; and A3, and B52 (HF 0.0168, P < 0.001; and HF 0.0130, P < 0.05, respectively).

The common HLA-A and -B HFs in positive LD in the main three tribes of the study subjects (Gaalia, Nile Nubians and Johyna) are shown in [Table 6].
Table 6: Haplotype frequencies of Gaalia, Johyna and Nile Nubian tribes.

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   Discussion Top


A few studies in the histocompatibility complex of Arab and Negroid Sudanese had been done previously. [4],[5] The present study provides data on the incidence, inheritance, and haplotype association of WHO-recognized HLA-A, -B, -DR and -DQ locus antigens in this population. Since consanguineous marriages are customary among the Sudanese people, we expected to find a relatively high homozygeity based on the observations in previous studies in other populations where intermarriage is found. [7] In contrast to our expectations, a wide variety of HLA antigens were found, with most of the antigens occurring at low frequency and most individuals were heterozygous. It is unclear whether there has been some selective advantage of major histocompatibility complex heterozygosis in the population, or whether the heterozygosis reflects recent tribal admixture. In this study, we observed high frequency of HLA-A2, A30, A3, A24, A1 and A68. There are very few HLA studies in Arab populations, in one of which A2, A30 and A1 were observed in Jordanian population at a GF of 0.134, 0.090 and 0.790, respectively. [8] This is relatively the same GF in our study. Similarly, A2, A24, and A30 were found in high frequency among Tunisians and A2 among those in United Arab Emirates (UAE) and geographically related Arabs, Iranians and Asians, all living in the UAE. [9] There are clear reductions in the normal frequencies of A36, A43, A66 and A69 antigens in the A locus among the study subjects compared to other black populations in South African Blacks, Zimbabweans and Nigerians. [10] Among the B locus specificities in the study subjects, B51 and B35 GFs were 0.092 and 0.068, respectively, but in the Jordanian population, the GFs were 0.083 and 0.066, [7] and in Pakistani populations, the GFs were approximately the same. [11]

Results obtained in class II antigen typing suggested that the most prevalent DR antigens in our Sudanese population were DR13 and DR15, which are also the reported AFs (more than 0.300) in all African countries except Algeria and Mali. [12] Most of the serologically well-defined specificities are present in this population. The linkage disequilibria seen in other populations [13] are also found here but with a few exceptions. DR1 shows a significant decrease in Sudanese subjects compared to the other African Blacks. [14] In this study, the most common DR2 split was DR15 (0.170), which was also reported in Malawi, South African Blacks, [9] Kenya, [15] and Nigeria, [16] but it is rare in Gambia. DR3, which is present in our study subjects with a GF 0.150, was observed in Saudi [17] and Kuwaiti [18] Arabs in approximately the same GF. DR17 is the most common DR3 subgroup (88%), a subgroup most often seen in Caucasians, while DR18 subgroup was observed in South African Blacks. [19] DR4 is usually observed in association with DQ03, DR53 and DQ04, DR53. [20] However, in this study, DR4 was observed with a GF of 0.051 and was found to be associated with DQ3 and DR53 and never with DQ4 and DR53 as found in Jordanian Arabs who have a GF (0.196). [21] In this study, the majority of the DR5 split was DR11 with a GF (0.135), which was also observed in the black population from Zaire, [13] while DR12, the other split of DR5 shows a decreased frequency in both populations. Always DR08 is associated with DQ4 in Caucasians (97%), [22] but here DR8 is found to be associated with DQ3. In the ninth Histocompatibility Workshop, DR9 was generally associated with DQ3, although it was associated with DQ2 in some instances (WHO Nomenclature Committee 1984). In this study, DR9 frequency was very low (1.4%) and was found to be associated with DQ2 and DR53.

The most common HLA-A and -B haplotypes in positive LD in the study subjects were A24, B38; and A3, B52 (HF 0.0168, P < 0.001; and HF 0.0130, P < 0.05, respectively).

The HLA-B and -DR haplotypes in positive LD in the study subjects were B41, DR17; B39, DR7; B35, DR11; B35, DR4; and B50, DR7 (HF 0.005589, 0.007234, 0.010105, 0.003406 and 0.008579, respectively), this was not statistically significant (P > 0.5).

These results suggest that both class I and class II polymorphisms of the study subjects depict considerable heterogeneity, which reflects recent admixture of this group with neighboring Arabs and African populations.

 
   References Top

1.Hajjej A, Kaabi1 H, Sellami H, et al. The contribution of HLA class I and II alleles and haplotypes to the investigation of the evolutionary history of Tunisians. Tissue Antigens 2006;68:153-62.  Back to cited text no. 1
    
2.Probst CM, Bompeixe EP, Pereira NF, et al. HLA polymorphism and evaluation of European, African, and Amerindian contribution to the white and mulatto populations from Parana, Brazil. Hum Biol 2000;72:597-617.  Back to cited text no. 2
    
3.Ward FE, Jensen JB, Hadi A, Stewart A, Waa, Bayoumi RA. HLA genotypes and Variant Alleles in Sudanese Families of Arab-Negroid Tribal Origin. Hum Immunol 1989;24:239-51.  Back to cited text no. 3
    
4.Magzoub M, Stephens H, Sachs J, et al. The HLA-DP polymorphism in Sudanese controls and patients with insulin dependent diabetic mellitus. Tissue Antigens 1992;40:64.  Back to cited text no. 4
    
5.Lewontin RC. The interaction of selection and linkage. General considerations: Heterotic models. Genetics 1964;49:49-67.  Back to cited text no. 5
    
6.Guo S, Thompsom E. Performing the exact test of Hardy-Weinberg proportions for multiple alleles. Biometric 1992;48:361-72.  Back to cited text no. 6
    
7.Ward FE, Bias WB, Reisner EG, Bo D. HLA specificities among old order Amisha genetic isolate in Dausset, Colambani. Histocompatibility testing Copenhagen, Munksgard, (eds) 1973:93.  Back to cited text no. 7
    
8.Sanchez-Velasco P, Karadshen NS, Garcia-Martin A, de Alegria CR, Leyva-Cobian F. Molecular analysis of HLA allelic frequencies and haplotypes in Jordanians and comparison with other related populations. Hum Immunol 2001;62:901-9.  Back to cited text no. 8
    
9.Valluei V, Mustafa M, Santhosh A, et al. Frequencies of HLA-A, HLA-B, HLA-DR, and HLA DQ phenotypes in the United Arab Emirates population. Tissue Antigens 2005;66:107-13.  Back to cited text no. 9
    
10.Du Toit ED, MacGregor KJ, Taljaard DG, Oudshoorn M. HLA-A, -B, -C, -DR and DQ polymorphisms in three South African population groups: South African Negroes, Cape Coloureds and South African Caucasoids. Tissue Antigens 1987;31:109-25.  Back to cited text no. 10
    
11.Zafar N, Khan S, Qadir A, Raza Y, Naqvi A, Rizvi A. HLA frequencies in Pakistani population groups. J Pak Med Assoc 1996;46(1):12-3.  Back to cited text no. 11
    
12.Kalidi I, Fofana Y, Rahly AA, et al. Study of HLA antigens in a population of Mali (West Africa). Tissue Antigens. Tissue Antigens 1988;31:98-102.  Back to cited text no. 12
    
13.Schreuder G, Marsh S, Charron D, Fauchet R. Structure and general organization of the Allele and Haplotype Society components, In: Genetic diversity of HLA, Functional and Medical Implication, Proceedings of the Twelfth International Histocompatibility Workshop and Conference. EDK Medical and Scientific Publisher I (ed. Charron, D.) 1997;3.  Back to cited text no. 13
    
14.Halle L, Mbayo K, Lurhuma Z, Salmon D, Martageix C, Castellano F. HLA-A, -B, -C, -DR and DQ polymorphism in Zairians. Tissue Antigens 1994;4 4:196-9.  Back to cited text no. 14
    
15.Hill A, Allsopp C, Kwiatkowski D, et al. Extensive genetic diversity in the HLA class II region of Africans, with a focally predominant allele, DRB1* 1304. Proc Nat Acad Sci USA 1992;89:2277-81.  Back to cited text no. 15
    
16.Okoye RC, Ollier W, Jaraquemada D, et al. HLA-D region heterogeneity in a Nigerian population. Tissue Antigen 1989;33:445-56.  Back to cited text no. 16
    
17.Al-Arfaj AS. Characteristics of rheumatoid arthritis relative to HLA-DR in Saudi Arabia. Saudi Med J 2001;22:595.  Back to cited text no. 17
    
18.Haider MZ, Zahid MA, Dalal HN, Razik MA. Human leukocyte antigen (HLA) DRB1 alleles in Kuwaiti Arabs with schizophrenia. Am J Med Genet 2000;96:870-2.  Back to cited text no. 18
    
19.Oudshoorn M, Martell RW, Crafford SD, May R, Dutoit ED. The polymorphism of HLA-DR3 in South African population. Hum Immunol 1989;2 4:265-76.  Back to cited text no. 19
    
20.Nahas R, Deghaide NH, Donad EA, Foss MC. Frequency of HLA Class II DR and DQ antigens in Brazilian patients with type I diabetes. Medicina Ribeirão Preto 2000;33:37-41.  Back to cited text no. 20
    
21.Sanchez-Velasco P, Karadsheh NS, Garcia-Martin A, Ruíz de Alegría C, Leyva-Cobián F. Molecular analysis of HLA allelic frequencies and haplotypes in Jordanians and comparison with other related populations. Hum Immunol 2001;62(9):901-9.  Back to cited text no. 21
    
22.Lee TD. "Distribution of HLA antigens in North American Caucasians, North American Blacks and Orientals" In Lee, J. (eds), The HLA System, A New Approach springerverlag, New York, 1990;141-78.  Back to cited text no. 22
    

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Correspondence Address:
Mohamed El Imam
Faculty of Medicine, University of Gezira, P.O. Box 20 Medani
Sudan
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PMID: 21743245

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]

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