Dataset Information

Distribution of HLA-B Alleles and Haplotypes in Qatari: Recommendation for Establishing Pharmacogenomic Markers Screening for Drug Hypersensitivity.

ABSTRACT: Human leukocyte antigen (HLA) proteins are present at the cellular surface of antigen-presenting cells and play a crucial role in the adaptive immune response. Class I genes, specifically certain HLA-B alleles, are associated with adverse drug reactions (ADRs) and are used as pharmacogenetic markers. Although ADRs are a common causes of hospitalization and mortality, the data on the prevalence of HLA-B pharmacogenetics markers in Arab countries are scarce. In this study, we investigated the frequencies of major HLA-B pharmacogenomics markers in the Qatari population. Next-generation sequencing data from 1,098 Qatari individuals were employed for HLA-B typing using HLA-HD version 1.4.0 and IPD-IMGT/HLA database. In addition, HLA-B pharmacogenetics markers were obtained from the HLA Adverse Drug Reaction Database. In total, 469 major HLA-B pharmacogenetic markers were identified, with HLA-B*51:01 being the most frequent pharmacogenetic marker (26.67%) in the Qatari population. Moreover, HLA-B*51:01 is associated with phenytoin- and clindamycin-induced ADRs. The second most frequent pharmacogenetic marker was the HLA-B*58:01 allele (6.56%), which is associated with allopurinol-induced ADRs. The third most frequent pharmacogenetic marker was the HLA-B*44:03 allele, which is associated with phenytoin-induced ADRs. The establishment of a pharmacogenetics screening program in Qatar for cost effective interventions aimed at preventing drug-induced hypersensitivity can be aided by the highly prevalent HLA-B pharmacogenetic markers detected here.

SUBMITTER: Dashti M

PROVIDER: S-EPMC9393242 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Distribution of HLA-B Alleles and Haplotypes in Qatari: Recommendation for Establishing Pharmacogenomic Markers Screening for Drug Hypersensitivity.

Dashti Mohammed M Al-Matrouk Abdullah A Channanath Arshad A Hebbar Prashantha P Al-Mulla Fahd F Thanaraj Thangavel Alphonse TA

Frontiers in pharmacology 20220808

Human leukocyte antigen (HLA) proteins are present at the cellular surface of antigen-presenting cells and play a crucial role in the adaptive immune response. Class I genes, specifically certain HLA-B alleles, are associated with adverse drug reactions (ADRs) and are used as pharmacogenetic markers. Although ADRs are a common causes of hospitalization and mortality, the data on the prevalence of HLA-B pharmacogenetics markers in Arab countries are scarce. In this study, we investi ...[more]

PMID: 36003520

Similar Datasets

Project description:Human leukocyte antigens (HLA) diversity has a tremendous impact on shaping the transplantation practices, transfusion-associated graft versus host disease prevention strategies, and host-pathogen interactions. Here, we conducted a retrospective study of HLA class I and class II homozygosity at allelic and haplotype levels in unrelated individuals genotyped from 2012 to 2016 in a tertiary hospital in the capital of Saudi Arabia. Among 5,000 individuals, 2,773 individuals meet inclusion criteria and were retrospectively analyzed for HLA-A, -B, -C-DRB1, and -DQB1 homozygosity at allelic and haplotype levels. HLA molecular typing was performed using a commercial reverse sequence-specific oligonucleotide (rSSO) kit. We were able to identify 15 HLA-A, 20 HLA-B, 11 HLA-C, 13 HLA-DRB1, and five HLA-DQB1 homozygous alleles demonstrating a very low genetic diversity in the Saudi population. The highest homozygosity in HLA class I was found in locus C followed by A and B (20.3% > 16.1% > 15.5%; p < 0.001) where the most homozygote alleles were A*02 (9.2%), B*51 and B*50 (5.7% and 3.7%), and C*07, C*06, and C*15 (7.2%, 5.48%, and 3.3%) and in HLA class II, the highest homozygosity was found in locus DQB1 compared to DRB1 (31.71% > 19.2%; p < 0.001), with the most common homozygote alleles being DRB1*07 and DRB1*04 (5.33% and 4.2%) and DQB1*02, DQB1*06, and DQB1*03 (13.55%, 7.92%, and 7.64%). The frequency of finding an individual with one homozygote allele was (24.6%), two homozygote alleles (13.5%), three homozygote alleles (4.7%), four homozygote alleles (3.4%), and five alleles were (4.8%). The most frequent homozygote haplotypes are A*23∼C*06∼B*50∼DRB1*07∼DQB1*02 and A*02∼C*06∼B*50∼DRB1*07∼DQB1*02. This study shows low diversity of both class I and II alleles and haplotypes in the Saudi population, which would have a significant impact on shaping the transplantation practices, transfusion-associated graft versus host disease prevention strategies, and host-pathogen interactions.

Project description:IntroductionThe human leukocyte antigen (HLA) region on chromosome 6p21 is well known to carry the most important genetic factors in susceptibility to psoriasis. Different HLA alleles and haplotypes have been reported to be associated with psoriasis in different populations. Psoriasis has a variable age of onset and, based on this, it can be classified into two types; type I with age of onset before 40 years of age and type II with age of onset after 40 years of age. The objective of this study was to determine the association of HLA class I and class II alleles and haplotypes with disease and stratification using age of onset in Pakistani psoriatic patients.MethodsA group of 603 individuals (326 cases and 277 controls) were analyzed for HLA class I and II alleles and haplotype association by sequence specific PCR. The association was further analyzed according to the age of onset of the patients.ResultsWe found that HLA alleles B*57 and Cw*06:02, DQB1*03:03:02 are strongly associated with early onset psoriasis, while alleles B*15, DRB1*13:02 and DQB1*03:03:02 are associated with late-onset psoriasis. Cw*06:02 allele was not associated with late-onset psoriasis patients. Allele DQB1*03:03:02 had the highest odds ratio in all patients. We found a novel association specifically with late-onset psoriasis samples with the haplotype HLA-A*11; B*15; Cw*04; DRB1*15; DQB1*05 (Pc = 3.60 × 10-7). We also found strong association with previously reported extended haplotype EH-57.1: HLA-B*57; Cw*06:02; DRB1*07:01; DQB1*03:03:02 in all our patients (Pc = 8.34 × 10-07).ConclusionOur results show that different HLA class I and II alleles and haplotypes are associated with psoriasis at different age of onset. In this study, we have reported novel alleles and haplotype association with late-onset psoriasis. Our data confirm the previous strong associations with HLA alleles and haplotypes and also reports novel alleles and haplotype association in Pakistani psoriasis patients.

Dataset Information

Distribution of HLA-B Alleles and Haplotypes in Qatari: Recommendation for Establishing Pharmacogenomic Markers Screening for Drug Hypersensitivity.

Publications

Distribution of <i>HLA-B</i> Alleles and Haplotypes in Qatari: Recommendation for Establishing Pharmacogenomic Markers Screening for Drug Hypersensitivity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets