Glutathione-S-transferase genetic polymorphism and risk of hepatotoxicity to antitubercular drugs in a North-African population: A case-control study

Chbili, Chahra; Fathallah, Neila; Laadhari, Chayma; Ouni, Bouraoui; Saguem, Saâd; Fredj, M. Ben; Ahmed, Ashir; Saad, Helmi Ben; Salem, Chaker Ben

doi:10.1016/j.gene.2021.146019

Cited by 2 publications

(1 citation statement)

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“…Homozygosity of GSTT1 or GSTM1 null genotypes cause lack of enzyme activity thus leading to the accumulation of the toxic intermediates of Isoniazid metabolisms and hepatotoxins. A statistically significant association between GSTM1 and GSTT1 double null genotypes, and the risk of anti-tubercular drug hepatotxicity was found (p = 0.033) between cases and controls 70 . This genetic variable could be used to develop a pharmacokinetic model of isoniazid concentration in order to maximize the probability of achieving its desired therapeutic concentration and avoid it toxicity in the Tunisian population 71 .…”

Section: Discussionmentioning

confidence: 92%

Ethnic and functional differentiation of copy number polymorphisms in Tunisian and HapMap population unveils insights on genome organizational plasticity

Romdhane,

Kefi,

Mezzi

et al. 2024

Sci Rep

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Admixture mapping has been useful in identifying genetic variations linked to phenotypes, adaptation and diseases. Copy number variations (CNVs) represents genomic structural variants spanning large regions of chromosomes reaching several megabases. In this investigation, the “Canary” algorithm was applied to 102 Tunisian samples and 991 individuals from eleven HapMap III populations to genotype 1279 copy number polymorphisms (CNPs). In this present work, we investigate the Tunisian population structure using the CNP makers previously identified among Tunisian. The study revealed that Sub-Saharan African populations exhibited the highest diversity with the highest proportions of allelic CNPs. Among all the African populations, Tunisia showed the least diversity. Individual ancestry proportions computed using STRUCTURE analysis revealed a major European component among Tunisians with lesser contribution from Sub-Saharan Africa and Asia. Population structure analysis indicated the genetic proximity with Europeans and noticeable distance from the Sub-Saharan African and East Asian clusters. Seven genes harbouring Tunisian high-frequent CNPs were identified known to be associated with 9 Mendelian diseases and/or phenotypes. Functional annotation of genes under selection highlighted a noteworthy enrichment of biological processes to receptor pathway and activity as well as glutathione metabolism. Additionally, pathways of potential concern for health such as drug metabolism, infectious diseases and cancers exhibited significant enrichment. The distinctive genetic makeup of the Tunisians might have been influenced by various factors including natural selection and genetic drift, resulting in the development of distinct genetic variations playing roles in specific biological processes. Our research provides a justification for focusing on the exclusive genome organization of this population and uncovers previously overlooked elements of the genome.

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Section: Discussionmentioning

confidence: 92%