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RENAL DATA FROM ASIA-AFRICA |
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| Year : 2011 | Volume
: 22
| Issue : 4 | Page : 834-840 |
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| HLA polymorphism in Sudanese renal donors |
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Ameer M Dafalla1, DJ McCloskey2, Almutaz A Alemam1, Amel A Ibrahim1, Adil M Babikir1, Nagla Gasmelseed1, Mohamed El Imam3, Ahmed A Mohamedani4, Mubarak M Magzoub1
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 Publication | 9-Jul-2011 |
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 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 2021 Mar 7];22:834-40. Available from: https://www.sjkdt.org/text.asp?2011/22/4/834/82738 |
| Introduction | |  |
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 | | |
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 | | |
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 | | |
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 | | |
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 | | |
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.
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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 
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6] |
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