Allelic Variants Research Articles

Association of the HLA DQA1*05 allelic gene variants with immunogenicity to anti-TNF therapeutics - important differences between infliximab and adalimumab.

Association of the HLA DQA1*05 allelic gene variants with immunogenicity to anti-TNF therapeutics - important differences between infliximab and adalimumab.

ABC Family Gene Polymorphisms and Cognitive Functions Interact to Influence Antidepressant Efficacy.

The importance of identifying relevant indicators of antidepressant efficacy is highlighted by the low response rates to antidepressant treatment for depression. The ABC gene family, encoding ATP-dependent transport proteins facilitating the transport of psychotropic drugs, has drawn attention. This study delved into the relationship between antidepressant efficacy and seven single nucleotide polymorphisms of ABCB1 and ABCB6 genes. A total of 549 depressed patients participated in the study, and all completed a 6-week course of antidepressant treatment. Cognitive function was assessed at baseline and post-treatment. Patients were categorized based on post-treatment HAMD-17 scores (with HAMD≤7 indicating remission), and comparisons were made between different groups in terms of allelic gene frequencies and genotypes. Logistic regression was used to explore the interaction between cognitive function and genotype on efficacy. Dual-luciferase reporter assays were performed to compare the regulatory effects of rs1109866 allele variants on the ABCB6 promoter. There were no notable differences in allelic gene frequencies and genotypes between the remission and non-remission groups. Nonetheless, a significant interaction was identified between the rs1109866 genotype and language fluency-related indicators concerning efficacy (p=0.029) before correction. The dual-luciferase reporter assays demonstrated markedly higher fluorescence intensity of rs1109866-C compared to that of rs1109866-T (p<0.001). Relying solely on genetic polymorphisms of ABC family genes as predictors of antidepressant treatment response may not be sufficient. However, the interaction between the rs1109866 and cognition plays a pivotal role. The potentially enhanced transcriptional activity of rs1109866-C might offer insight into its impact on antidepressant efficacy.

PharmFreq: a comprehensive atlas of ethnogeographic allelic variation in clinically important pharmacogenes.

Genetic polymorphisms in drug metabolizing enzymes, drug transporters as well as in genes encoding the human major histocompatibility complex contribute to inter-individual differences in drug efficacy and safety. The extent, pattern and complexity of such pharmacogenetic variation differ drastically across human populations. Here, we present PharmFreq, a global repository of pharmacogenetic frequency information that aggregates frequency data of 658 allelic variants from over 10 million individuals collected from>1200 studies across 144 countries. Most investigations were conducted in East Asian and European populations, accounting for 29.4 and 26.6% of all studies, respectively. We find that the number of studies per country and aggregated cohort size correlated significantly with population size (R=0.55, P=3*10-9) and country gross domestic product (R=0.43, P=2*10-6) with overall population coverage varying between 5% in Estonia to<0.001% in many countries in Sub-Saharan Africa and Asia. All frequency data are openly accessible via a web-based interactive dashboard at pharmfreq.com that facilitates the exploration, visualization and analysis of country- and population-specific data and their inferred phenotypic consequences. PharmFreq thus presents a comprehensive, freely available resource for pharmacogenetic variant frequencies that can inform about ethnogeographic pharmacogenomic diversity and reveal important inequities that help to focus future research efforts into underrepresented populations.

Case Report: Allelic and biallelic variants in coagulation factor XI cause factor XI deficiency

Factor XI deficiency is a rare inherited coagulation disorder with an estimated prevalence of affecting 1 in 1 million. It is characterized by mild and variable bleeding phenotypes, including bruises, nosebleeds, hematuria, and postpartum hemorrhage. It can be caused by either allelic or biallelic variants in coagulation factor XI (F11). Coagulation factor XI is a glycoprotein that circulates in plasma as a non-covalent complex with high-molecular-weight kininogen. It is converted to an active protease, coagulation factor XIa, which participates in blood coagulation as a catalyst. In this study, we recruited a family with Factor XI deficiency and identified two F11 variants using whole-exome sequencing. One (NM_000128.4: c.841C&amp;gt;T, p.Q281X) was a known variant, and the other (NM_000128.4: c.1832T&amp;gt;G, p.V611G) had not been reported. In addition, we compiled the characteristics of known missense variants in coagulation factor XI. Our findings enriched the variant spectrum of Factor XI deficiency and contributed to the genetic counseling and molecular diagnostics of Factor XI deficiency.

Evaluation of population genetics of Moringa oleifera Provenances from Coastal Kenya using Single Nucleotide Polymorphism (SNPs) markers

Population genetics analysis is a prerequisite to understanding how and why genotypes and allele frequencies and change over time between and within populations. Consequently, it offers insight into the process of evolutionary change and makes it possible to map variants linked to traits that differ among populations. In the present study, Single Nucleotide Polymorphisms (SNPs) markers were utilized to study the genetic characterization of 17 provenances from the Coast region of Kenya. 164 genotypes of Moringa oleifera were selected from 17 populations and genome sequencing undertaken utilizing genotyping by sequencing (GBS). Identification of polymorphisms (SNP Calling) in the selected genotypes and population genetic studies were carried out. SNP calling was done by Illumina’s SNP caller algorithm in the CASAVA software. 20,921 SNPs were called with an average call rate of 0.82. Average polymorphsm content (PIC) for the SNPs was 0.24 and reproducibility was 0.98. A phenetic tree was constructed using a neighbor-joining approach using DArT R. For the population genetics analysis, F statistic (Fst) utilising the functions StAMPP package in DArT R was performed whereby Gede and Samburu exhibited the least heterozygosity/correlation with a value of 0.0003 whereas Pwani University and Samburu had the highest correlation of genes at 0.37. Euclidean was used as a measure distance, and the average distance between the populations was 33.024. The molecular variance analysis (AMOVA) described a lower, 2.55%, variation within the population and 2.73% among the populations. The high similarity between the genotypes could be attributed to the Moringa plants in the various provenances having the same ancestry. This study may help identify links between gene allelic forms and phenotypes, allowing the alleles to be connected to desired characteristics such as rapid growth and high yield (functional analysis), because of the high frequency of SNPs and their role as a source of allele variations.

Experience of Genotyping of the Class 1 Major Histocompatibility Complex Genes in a Rhesus Macaques Collection

The utility of animal models in preclinical research depends on the completeness of our knowledge about these models. Nonhuman primates are the closest animal model to humans, available for preclinical evaluation of biotechnological products. The lack of immunogenetic characteristics of the primates used in a particular study significantly limits the possibilities of analyzing the results obtained. The availability of information about the haplotype of the major histocompatibility complex (MHC) increases the overall significance of the model. Genotyping of primates at the MHC locus by DNA analysis is excluded, since the representation of individual MHC proteins depends on the level of their expression in immune cells, rather than on their presence in the genome. Therefore, the genotyping of primates at the MHC locus is carried out by analyzing mRNA encoding allelic variants of proteins. This work presents the results of genotyping of a sample of rhesus macaques from the collection of the Kurchatov Complex of Medical Primatology by a next-generation sequencing technology using an IonProton sequencer.

Functional significance of CYP2B6 gene rare allelic variants identified in Japanese individuals

Cytochrome P450 2B6 (CYP2B6) catalyzes the metabolism of many drugs, including efavirenz and propofol. Genetic polymorphisms in CYP2B6 alter its enzymatic activity and substantially affect its pharmacokinetics. High-frequency variants, such as CYP2B6*6, are associated with the risk of developing side effects due to reduced CYP2B6 activity. However, the impact of rare alterations on enzyme function remains unknown, and some of these variants may significantly decrease the CYP2B6 activity. Therefore, in this study, we evaluated in vitro the functional alterations in 29 missense variants of the CYP2B6 gene identified in 8,380 Japanese individuals. Wild-type CYP2B6 and 29 rare CYP2B6 variants were transiently expressed in mammalian cells. The expression levels of variant CYP2B6 proteins in the microsomal fractions extracted from 293FT cells were assessed using western blotting and reduced-carbon monoxide difference spectroscopy, and a specific peak at 450 nm was detected in the wild-type and 19 variants. Furthermore, kinetic parameters were determined by assaying the reactions with efavirenz and propofol and quantifying the metabolite concentrations. We found that 12 variants had significantly lower or abolished enzymatic activity with both the substrates. In silico three-dimensional docking and molecular-dynamics simulations suggested that these functional changes were due to conformational changes in essential regions, such as the heme-binding site and ligand channels involved in transporting substrates to the active site. These findings have implications for predicting the plasma concentrations of CYP2B6 substrates and controlling their side effects.

A QTL on chromosome 17 identified by Genome-Wide Association Mapping controls postharvest cold tolerance of Cucurbita pepo L.

The worldwide cultivated Cucurbita pepo L. is one of the most diverse species in the plant kingdom. In this study, chilling tolerance over a wide range of cultivars was characterized to discover the allelic variants to improving the postharvest quality of the immature fruit during cold storage. For this purpose, fruits from 126 accessions of worldwide origin have been evaluated for weight loss and chilling injury after 3, 7 and 14 days of cold storage, classifying them into tolerant, partially tolerant, and sensitive accessions. To verify this classification, antioxidant capacity and lipid peroxidation (MDA) of contrasting accessions (tolerant vs. sensitive) were assessed. The antioxidant capacity significantly decreased during cold storage in the sensitive accessions, while it was maintained in tolerant accessions. Additionally, the sensitive accessions presented a higher accumulation of MDA during this period. Finally, a GWAS analysis using GBS data available in CuGenDBv2, combined with weight loss percentage data, led to the identification of a candidate QTL located on chromosome 17 that regulates postharvest cold tolerance in zucchini. The region contains four SNPs whose alternative alleles were significantly associated with lower weight loss percentage and chilling injury indices during cold storage. Two SNPs are located in the 3' UTR region of the gene CpERS1, a gene involved in ethylene perception. The other two SNPs generate missense mutations in the coding region of a Pectin methyl esterase inhibitor gene (CpPMI). The role of this QTL and these variants in chilling tolerance is discussed.

A natural allelic variant of GmSW17.1 confers high 100-seed weight in soybean

A natural allelic variant of GmSW17.1 confers high 100-seed weight in soybean

Identification and molecular marker development for peel color gene in melon (Cucumis melo L.)

Peel color is an important appearance quality of melons that greatly affects consumer preferences. In this study, a near-isogenic line NIL-G (dark green peel) was generated from B8 (grey-green peel) and B15 (white peel). The F2 population constructed by crossing NIL-G and B15 was used to study the inheritance pattern of peel color, and bulked-segregant analysis sequencing (BSA-seq) was employed to identify the interval in which the target gene was located. Genetic analysis results showed that the dark green peel trait at maturity is controlled by a dominant gene. BSA-seq and molecular markers were used to localize the candidate gene in a 263.7 kb interval of chromosome 4, which contained the CmAPRR2 gene with known functions. Moreover, allelic sequence analysis revealed four SNP variations of the CmAPRR2 gene in B15, of which SNP.G614331A was located at the junction of the 6th exon and 6th intron. The G-to-A mutation caused alternative splicing of the transcript of CmAPRR2 in B15, generating two transcripts (CmAPRR2-A and CmAPRR2-B) with premature termination codons. Furthermore, the Kompetitive Allele Specific PCR (KASP) marker, APRR2-G/A, was developed based on this SNP and shown to co-segregate with the peel color phenotype in the F2 population. Compared to white-peel B15, the expression level of CmAPRR2 in dark green peel NIL-G was higher at each growth stage. Therefore, CmAPRR2 may be the key gene controlling the fruit color of melons. Overall, this study identified a novel allelic variant of CmAPRR2 that leads to white peel formation in mature melons. The study also provides a theoretical basis for further research on the gene regulatory mechanism of melon peel colors and may promote the future use of molecular marker-assisted selection to modify melon peel colors.

Relationship of Retroelements with Antiviral Proteins and Epigenetic Factors in Alzheimer's Disease

Genetic factors such as allelic variants of the PSEN1, PSEN2, APP, and APOE genes play an important role in Alzheimer's disease development. Still, they cannot explain all cases of the disease and cannot form the basis for effective treatment methods for the pathology. Alzheimer's disease is the most common neurodegenerative disease, so identifying new mechanisms of pathogenesis may reveal new ways of treating it. Since Alzheimer's disease is associated with aging, the hypothesis is proposed that an important trigger mechanism for it is the pathological activation of retroelements during aging, leading to epigenetic changes. This is due to the role of retroelements in gene expression regulation and the origin of long noncoding RNAs and microRNAs from transposons, changes in the expression of which are observed both during aging and Alzheimer's disease. Normally, activation of retroelements is observed in hippocampal neuronal stem cells, which is necessary for epigenetic programming during neuronal differentiation. Direct changes in the expression of retroelements in Alzheimer's disease have also been described. It has been suggested that aging is a trigger for the development of Alzheimer's disease due to the pathological activation of retroelements. To confirm this hypothesis, an analysis of specific microRNAs associated with Alzheimer's disease and aging in the MDTE DB (microRNAs derived from Transposable elements) database was conducted. As a result, identified expression changes in Alzheimer's disease of 37 individual microRNAs derived from retroelements (25 from LINE, 7 from SINE, 5 from HERV), of which 12 changes expression during physiological aging, which confirms my hypothesis that the activation of retroelements during physiological aging is a driver for Alzheimer's disease. This is evidenced by the defeat of diseases mainly by the elderly and older adults. Since 3 of the 12 miRNAs associated with aging and Alzheimer's disease originated from SINE/MIRs that evolved from tRNAs, the role of tRNAs and the tRFs and tRNA halves derived from them in the development of Alzheimer's disease, which are evolutionarily closely related to retroelements was described. These results are promising for targeted disease therapy in the mechanisms of RNA-directed DNA methylation with possible complex use of retroelement enzyme inhibitors. Additional evidence for the role of retroelements in the development of Alzheimer's disease is that overexpression of tau, which has antiviral properties, with its interaction with beta-amyloid leads to dysregulation of retroelements, and in tauopathies, activation of ERV is determined. At the same time, the effect of retroelements as inducers of proteinopathy and tau aggregation has been described. In addition, HIV and herpes viruses, which affect beta-amyloid and tau protein, are also activators of retroelements. Also, polymorphisms associated with Alzheimer's disease are located mainly in intronic and intergenic regions where retroelements are located, affecting changes in their activity.

Evaluation of genetic purity of parental lines and hybrids of sunflower

A high level of genetic purity, preservation and maintenance of genetic uniformity of parental lines and hybrids are necessary conditions in heterotic breeding of a sunflower. The main method for determining the genetic purity of sunflower genotypes is the method of field soil control with the assessment of plants based on morphological traits. The purpose of the experiment was to study the possibility of effectively using the method of electrophoresis of storage proteins of seeds in determining the typicalness of parental lines and the hybridity of sunflower hybrids. 13 samples of maternal sterile lines, 26 samples of hybrids were analyzed using the methods of soil control and the method of analyzing the spectra of seed storage proteins. Research results have proven the highly effective method of electrophoresis of storage proteins in determining the genetic purity of seed of lines and hybrids. The concurrence between the results of the two methods in determining genetic purity was 84.4% for maternal sterile lines, 69.2% for hybrids. The method of analysis allelic variants of helianthinin increased the reliability of the results obtained in determining the level of genetic purity of lines and hybrids by 7.7%. The presence of atypical plants in sunflower crops on the trait of “high” and “low” leads to unreliable, increased indicators of the level of genetic purity by 23.1% with the method of analysis of the spectra of storage proteins of sunflower seeds. The electrophoresis method, based on the analysis of the spectra of storage proteins, can be used as a rapid method in determining the genetic purity of sunflower genotypes.

UGT1A1 and BLVRA allele and genotype variants in neonatal patients with hyperbilirubinemia in southern China

We explore the allele and genotype distribution of UGT1A1 and BLVRA variants in individuals affected by neonatal hyperbilirubinemia in southern China. Blood specimens were collected from 240 neonates: 126 cases of hyperbilirubinemia and 114 healthy controls. Serum levels of total protein, albumin, bilirubin (total and direct), urea nitrogen, creatinine, and other biochemical parameters were quantified using a biochemical analyzer. Nine UGT1A1 and five BLVRA genetic variants were genotyped using flight time mass spectrometry. The allele and genotype frequencies of these variants and their associations with neonatal hyperbilirubinemia were analyzed. The genotype frequencies of CC and CG for the UGT1A1 variant rs11888492 in the hyperbilirubinemia group were 90.48% and 9.52%, respectively (P = 0.001), in comparison with the control group. The C and G allele frequencies of rs11888492 in the hyperbilirubinemia group were 95.24% and 4.76%, respectively (P = 0.023). Similarly, in the hyperbilirubinemia group, the genotype frequencies for the UGT1A1 variant rs4148325 were 90.48% CC, 8.73% CT, and 0.79% TT (P = 0.001), with corresponding allele frequencies of 94.84% for C and 5.16% for T (P = 0.002). No notable distinctions were detected for other variants. Newborns carrying the CC genotype of rs11888492 exhibited higher total bilirubin (TBIL) levels than those carrying the GG genotype (P = 0.034), whereas newborns carrying the CC genotype of rs4148325 displayed higher TBIL levels than those carrying the CT genotype (P = 0.003). The presence of the G allele at rs11888492 was found to be significantly correlated with a decreased likelihood of developing neonatal hyperbilirubinemia (odds ratio [OR]: 0.363; 95% confidence interval [CI] 0.169–0.777). Furthermore, a substantial reduction in the risk of neonatal hyperbilirubinemia associated with the CT genotype of rs4148325 were revealed (OR = 0.242; 95% CI 0.102–0.574). Additionally, an inverse relationship was identified between TBIL concentration and the quantity of genetic variants. The UGT1A1 variants rs11888492 and rs4148325 are strongly associated with neonatal hyperbilirubinemia in southern China.

Association of human leukocyte antigen allelic variants with hidradenitis suppurativa across Fitzpatrick skin types: a cross-sectional analysis

Association of human leukocyte antigen allelic variants with hidradenitis suppurativa across Fitzpatrick skin types: a cross-sectional analysis

Associations of different genotypes with the meat productivity of sheep

Identification of the potential to increasthe agricultural production of farm animals has become possible through the use of genomic selection methods. It is advisable to improve breeding and pedigree qualities of local breeds, since these have the best adaptability to the features of the natural and geographical conditions in a given area. He controlled slaughter of animals with different genotypes allowed us to determine their meat qualities, such as biological value, slaughter yield and slaughter weight. The ratio of slaughter weight and pre‐slaughter weight gives the slaughter yield in percent.PCR (polyamino acid chain reaction) using specific synthesised sets of oligonucleotides in the genotyping of experimental sheep populations was carried out in order to study the allelic variants of the CAST and GH genes.When studying the indices characterising body weight in sheep which have different genotypes, significant increases in the indices could be observed before the periods of driving to summer pastures (17.2 kg) and during lambing (25.8 kg). The lowest indices were noted during driving both from winter pastures to summer pastures and from summer pastures to winter pastures (30.5 kg).In the period before driving, the live weight index was higher in the CASTMM genotype by 5.8 %; upon arrival in the mountains the difference was 6.1 %; during lambing — 4.7 %; before leaving for winter pastures — 8.4 % and upon arrival at winter pastures — 9.5 %.

Ultrasensitive allele inference from immune repertoire sequencing data with MiXCR.

Allelic variability in the adaptive immune receptor loci, which harbor the gene segments that encode B cell and T cell receptors (BCR/TCR), is of critical importance for immune responses to pathogens and vaccines. Adaptive immune receptor repertoire sequencing (AIRR-seq) has become widespread in immunology research making it the most readily available source of information about allelic diversity in immunoglobulin (IG) and T cell receptor (TR) loci. Here we present a novel algorithm for extra-sensitive and specific variable (V) and joining (J) gene allele inference, allowing reconstruction of individual high-quality gene segment libraries. The approach can be applied for inferring allelic variants from peripheral blood lymphocyte BCR and TCR repertoire sequencing data, including hypermutated isotype-switched BCR sequences, thus allowing high-throughput novel allele discovery from a wide variety of existing datasets. The developed algorithm is a part of the MiXCR software. We demonstrate the accuracy of this approach using AIRR-seq paired with long-read genomic sequencing data, comparing it to a widely used algorithm, TIgGER. We applied the algorithm to a large set of IG heavy chain (IGH) AIRR-seq data from 450 donors of ancestrally diverse population groups, and to the largest reported full-length TCR alpha and beta chain (TRA; TRB) AIRR-seq dataset, representing 134 individuals. This allowed us to assess the genetic diversity within the IGH, TRA and TRB loci in different populations and to establish a database of alleles of V and J genes inferred from AIRR-seq data and their population frequencies with free public access through an online database.

Pharmacogenetic DPYD allele variant frequencies: A comprehensive analysis across an ancestrally diverse Iranian population.

Cancer treatment has improved over the past decades, but many cancer patients still experience adverse drug reactions (ADRs). Pharmacogenomics (PGx), known as personalized treatment, is a pillar of precision medicine that aims to optimize the efficacy and safety of medications by studying the germline variations. Germline variations in the DPYD lead to significant ADRs. The present cross-sectional study aims to evaluate the allele frequency of the DPYD gene variations in the Iranian population to provide insights into personalized treatment decisions in the Iranian population. The allele frequency of 51 pharmacogenetic variations in the clinically relevant DPYD was assessed in a representative sample set of 1142 unrelated Iranian individuals and subpopulations of different ethnic groups who were genotyped using the Infinium Global Screening Array-24 BeadChip. The genotyping assay revealed eight pharmacogenetic variants including DPYD rs1801265 (c.85T > C; DPYD*9A), rs2297595 (c.496A > G), rs1801158 (c.1601G > A; DPYD*4), rs1801159 (c.1627A > G; DPYD*5), rs1801160 (c.2194G > A; DPYD*6), rs17376848 (c.1896T > C), rs56038477 (c.1236G > A; HapB3), and rs75017182 (c.1129-5923C > G; HapB3) with minor allele frequency (MAF) ≥ 1%. The results of the study reveal significant genetic variations among Iranian population that could significantly influence clinical decision-making. These variants, with their potential to explain the substantial variability in drug response phenotypes among different populations, shed light on a crucial aspect of pharmacogenomics. These findings not only provide valuable insights but also inspire the design and implementation of future pharmacogenomic clinical trials, motivating further research in this crucial area.

Allelic variants confer Arabidopsis adaptation to small regional environmental differences.

Natural populations of Arabidopsis thaliana provide powerful systems to study the adaptation of wild plant species. Previous research has predominantly focused on global populations or accessions collected from regions with diverse climates. However, little is known about the genetics underlying adaptation in regions with mild environmental clines. We have examined a diversity panel consisting of 192 A. thaliana accessions collected from the Netherlands, a region with limited climatic variation. Despite the relatively uniform climate, we identified evidence of local adaptation within this population. Notably, semidwarf accessions, due to mutation of the GIBBERELLIC ACID REQUIRING 5 (GA5) gene, occur at a relatively high frequency near the coast and these displayed enhanced tolerance to high wind velocities. Additionally, we evaluated the performance of the population under iron deficiency conditions and found that allelic variation in the FE SUPEROXIDE DISMUTASE 3 (FSD3) gene affects tolerance to low iron levels. Moreover, we explored patterns of local adaptation to environmental clines in temperature and precipitation, observing that allelic variation at LA RELATED PROTEIN 1C (LARP1c) likely affects drought tolerance. Not only is the genetic variation observed in a diversity panel of A. thaliana collected in a region with mild environmental clines comparable to that in collections sampled over larger geographic ranges but it is also sufficiently rich to elucidate the genetic and environmental factors underlying natural plant adaptation.

Pesticide exposure and oxidative stress generation are linked to poor prognosis outcomes in breast cancer women carrying the allelic variant rs7438135 in the UGT2B7 gene.

Pesticide exposure is a risk factor for the development of several diseases, including breast cancer (BC). The enzyme UGT2B7 participate in detoxification of pesticides and the presence rs7438135 (G > A) variant in your gene increases its glucuronidation potential, contributing to oxidative stress metabolites neutralization. Here we investigated the impact of occupational pesticide exposure on the systemic oxidative stress generation from 228 women with BC depending on their UGT2B7 rs7438135 (G > A) status. q-PCR investigated the presence of the rs7438135 variant, and oxidative stress markers (lipid peroxidation levels, total antioxidant capacity-TRAP, and nitric oxide metabolites-NOx) were measured in plasma. Pesticide exposure induced significant augment in the systemic lipid peroxidation in the presence of the variant for several clinicopathological conditions, including tumors with high proliferation index (ki67) and with high aggressiveness. NOx was augmented in high ki67, positive progesterone receptors, high-grade and triple-negative/Luminal B tumors, and low-risk stratified patients. TRAP was depleted in young patients at menopause and those with triple-negative/Luminal B tumors, as well as those stratified as at low risk for death and recurrence. These findings showed that the presence of the variant was not able to protect from pesticide-induced oxidative stress generation in BC patients.

HLA-B allele frequencies and implications for pharmacogenetics in the Kuwaiti population.

We utilized the HLA-HD tool to extract, annotate, and analyse HLA-B alleles from the exome data of 561 Kuwaiti individuals, sequenced on the Illumina HiSeq platform. HLA typing was conducted using the HLA-HD tool with a reference panel from the IPD-IMGT/HLA database. The major HLA-B pharmacogenetic markers were obtained from the HLA Adverse Drug Reaction Database, focusing on alleles with significant ADR associations in published literature. The distribution of HLA-B alleles in the Kuwaiti population revealed that the most frequent alleles were HLA-B*50:01 (10.52%), HLA-B*51:01 (9.89%), HLA-B*08:01 (6.06%), HLA-B*52:01 (4.55%), HLA-B*18:01 (3.92%), and HLA-B*41:01 (3.65%). Notably, alleles HLA-B*13:01, HLA-B*13:02, HLA-B*15:02, HLA-B*15:13, HLA-B*35:02, HLA-B*35:05, HLA-B*38:01, HLA-B*40:02, HLA-B*44:03, HLA-B*51:01, HLA-B*57:01 and HLA-B*58:01 were identified with known associations to various ADRs. For example, HLA-B*51:01 was associated with clindamycin, phenobarbital, and phenytoin, and was found in 18% of individuals. Our study enriches the regional genetic landscape by delineating HLA-B allele variations within Kuwait and across the Arabian Peninsula. This genetic insight, along with the identification of markers previously linked to drug hypersensitivity, provides a foundation for future pharmacogenetic research and potential personalized medicine strategies in the region.