Pharmacogenomic profiling of variants affecting efficacy and toxicity of anti-infective medicines in a south Asian population from Sri Lanka

Background Anti-infective medicines are crucial for treating infections, but improper dosing can cause toxicity, resistance and treatment failure. Pharmacogenomics can address genetic variations affecting drug efficacy and safety. Despite the high burden of diseases like TB and HIV in Sri Lanka and...

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Veröffentlicht in:	BMC infectious diseases Jg. 25; H. 1; S. 153 - 12
Hauptverfasser:	Ranasinghe, Priyanga, Jeyapragasam, Hajanthy, Sirisena, Nirmala, Bhagya Hendalage, D. P., Dissanayake, Vajira H. W.
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London BioMed Central 01.02.2025 BioMed Central Ltd BMC
Schlagworte:	Adult Anti-infective agents Anti-Infective Agents - adverse effects Anti-Infective Agents - pharmacology Anti-Infective Agents - therapeutic use Anti-infectives Arylamine N-Acetyltransferase - genetics Dosage and administration Female Genetic aspects Genetic Variation HIV Humans Infectious Diseases Internal Medicine Male Medical Microbiology Medicine Medicine & Public Health Middle Aged Parasitology Pharmacogenetics Pharmacogenomic Variants Pharmacogenomics Pharmacology, Experimental Physiological aspects Polymorphism, Single Nucleotide South Asia South Asian People - genetics Sri Lanka Tropical Medicine Tuberculosis Sri Lanka Anti-infectives Tuberculosis HIV Sri Lanka Voriconazole South Asia Pharmacogenomics
ISSN:	1471-2334, 1471-2334
Online-Zugang:	Volltext
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Abstract	Background Anti-infective medicines are crucial for treating infections, but improper dosing can cause toxicity, resistance and treatment failure. Pharmacogenomics can address genetic variations affecting drug efficacy and safety. Despite the high burden of diseases like TB and HIV in Sri Lanka and South Asia, pharmacogenomic data for these populations are limited. This study aims to fill this gap by investigating pharmacogenomic variants in a South Asian population from Sri Lankan. Methods Pharmacogenomic data on anti-infective medicines were obtained from the PharmGKB database, selecting variants with evidence levels 1 A, 1B, 2 A, and 2B. Sri Lankan genetic data were sourced from an anonymized database of 670 Sri Lankans maintained by the Centre for Genetics and Genomics, Faculty of Medicine, University of Colombo. MAFs were compared between Sri Lankan sub-populations and global data from gnomAD, with statistical significance set at p < 0.05. Results MAFs of NAT2 gene rs1041983 and rs1799931 variants were, 43.7% (95%CI:41.1–46.4), 7.3% (95%CI:6.0-8.8), respectively. The UGT1A1 rs4148323 variant had a MAF of 3.5% (95%CI:2.6–4.6). In the CYP2B6 gene, 109 individuals were homozygous for the rs3745274 (poor metaboliser) variant, with a MAF of 39.6% (95%CI:37.0-42.3), while the rs34097093 and rs28399499 variants had no individuals homozygous for the variant (MAF: 0.2% [95%CI:0-0.5] (poor/intermediate metaboliser), and 0.1% [95%CI:0-0.4] (poor/intermediate metaboliser), respectively). The MAFs of the CYP2C19 rs12769205 (poor/intermediate metaboliser), rs4244285 (poor/intermediate metaboliser), rs3758581 (poor/intermediate metaboliser), and rs4986893 (poor/intermediate metaboliser) variants were 41.9% (95%CI:39.3–44.6), 41.9% (95%CI:39.2–44.7), 9.7% (95%CI:8.2–11.4), and 0.5% [(95%CI:0.2–1.1), respectively. Most variants showed significant differences compared to global populations, with some exhibiting higher frequencies, particularly when compared to Europeans. CYP2C19 rs12769205 and rs4244285 exhibited higher MAFs in Sri Lankans compared to both other South Asians and Europeans. The NAT2 rs1041983, NAT2 rs1799931, CYP2C19 rs4986893, CYP2C19 rs3758581, and CYP2B6 rs3745274 variants demonstrated significantly higher MAFs than in Europeans but not significantly different from South Asians. Conclusion This preliminary study identifies variants in NAT2 , UGT1A1 , CYP2B6 , and CYP2C19 genes relevant to the metabolism of anti-TB drugs, antiretrovirals, and voriconazole among Sri Lankans. Several variants, including CYP2C19 rs12769205 and rs4244285, showed higher MAFs, particularly in comparison to European populations, indicating potential differences in drug response. However, the nature of the study limits the ability to explore clinical correlations with the genotypes, therefore further research focusing on clinical correlation and functional validation is required.
AbstractList	Abstract Background Anti-infective medicines are crucial for treating infections, but improper dosing can cause toxicity, resistance and treatment failure. Pharmacogenomics can address genetic variations affecting drug efficacy and safety. Despite the high burden of diseases like TB and HIV in Sri Lanka and South Asia, pharmacogenomic data for these populations are limited. This study aims to fill this gap by investigating pharmacogenomic variants in a South Asian population from Sri Lankan. Methods Pharmacogenomic data on anti-infective medicines were obtained from the PharmGKB database, selecting variants with evidence levels 1 A, 1B, 2 A, and 2B. Sri Lankan genetic data were sourced from an anonymized database of 670 Sri Lankans maintained by the Centre for Genetics and Genomics, Faculty of Medicine, University of Colombo. MAFs were compared between Sri Lankan sub-populations and global data from gnomAD, with statistical significance set at p < 0.05. Results MAFs of NAT2 gene rs1041983 and rs1799931 variants were, 43.7% (95%CI:41.1–46.4), 7.3% (95%CI:6.0-8.8), respectively. The UGT1A1 rs4148323 variant had a MAF of 3.5% (95%CI:2.6–4.6). In the CYP2B6 gene, 109 individuals were homozygous for the rs3745274 (poor metaboliser) variant, with a MAF of 39.6% (95%CI:37.0-42.3), while the rs34097093 and rs28399499 variants had no individuals homozygous for the variant (MAF: 0.2% [95%CI:0-0.5] (poor/intermediate metaboliser), and 0.1% [95%CI:0-0.4] (poor/intermediate metaboliser), respectively). The MAFs of the CYP2C19 rs12769205 (poor/intermediate metaboliser), rs4244285 (poor/intermediate metaboliser), rs3758581 (poor/intermediate metaboliser), and rs4986893 (poor/intermediate metaboliser) variants were 41.9% (95%CI:39.3–44.6), 41.9% (95%CI:39.2–44.7), 9.7% (95%CI:8.2–11.4), and 0.5% [(95%CI:0.2–1.1), respectively. Most variants showed significant differences compared to global populations, with some exhibiting higher frequencies, particularly when compared to Europeans. CYP2C19 rs12769205 and rs4244285 exhibited higher MAFs in Sri Lankans compared to both other South Asians and Europeans. The NAT2 rs1041983, NAT2 rs1799931, CYP2C19 rs4986893, CYP2C19 rs3758581, and CYP2B6 rs3745274 variants demonstrated significantly higher MAFs than in Europeans but not significantly different from South Asians. Conclusion This preliminary study identifies variants in NAT2, UGT1A1, CYP2B6, and CYP2C19 genes relevant to the metabolism of anti-TB drugs, antiretrovirals, and voriconazole among Sri Lankans. Several variants, including CYP2C19 rs12769205 and rs4244285, showed higher MAFs, particularly in comparison to European populations, indicating potential differences in drug response. However, the nature of the study limits the ability to explore clinical correlations with the genotypes, therefore further research focusing on clinical correlation and functional validation is required. Background Anti-infective medicines are crucial for treating infections, but improper dosing can cause toxicity, resistance and treatment failure. Pharmacogenomics can address genetic variations affecting drug efficacy and safety. Despite the high burden of diseases like TB and HIV in Sri Lanka and South Asia, pharmacogenomic data for these populations are limited. This study aims to fill this gap by investigating pharmacogenomic variants in a South Asian population from Sri Lankan. Methods Pharmacogenomic data on anti-infective medicines were obtained from the PharmGKB database, selecting variants with evidence levels 1 A, 1B, 2 A, and 2B. Sri Lankan genetic data were sourced from an anonymized database of 670 Sri Lankans maintained by the Centre for Genetics and Genomics, Faculty of Medicine, University of Colombo. MAFs were compared between Sri Lankan sub-populations and global data from gnomAD, with statistical significance set at p < 0.05. Results MAFs of NAT2 gene rs1041983 and rs1799931 variants were, 43.7% (95%CI:41.1–46.4), 7.3% (95%CI:6.0-8.8), respectively. The UGT1A1 rs4148323 variant had a MAF of 3.5% (95%CI:2.6–4.6). In the CYP2B6 gene, 109 individuals were homozygous for the rs3745274 (poor metaboliser) variant, with a MAF of 39.6% (95%CI:37.0-42.3), while the rs34097093 and rs28399499 variants had no individuals homozygous for the variant (MAF: 0.2% [95%CI:0-0.5] (poor/intermediate metaboliser), and 0.1% [95%CI:0-0.4] (poor/intermediate metaboliser), respectively). The MAFs of the CYP2C19 rs12769205 (poor/intermediate metaboliser), rs4244285 (poor/intermediate metaboliser), rs3758581 (poor/intermediate metaboliser), and rs4986893 (poor/intermediate metaboliser) variants were 41.9% (95%CI:39.3–44.6), 41.9% (95%CI:39.2–44.7), 9.7% (95%CI:8.2–11.4), and 0.5% [(95%CI:0.2–1.1), respectively. Most variants showed significant differences compared to global populations, with some exhibiting higher frequencies, particularly when compared to Europeans. CYP2C19 rs12769205 and rs4244285 exhibited higher MAFs in Sri Lankans compared to both other South Asians and Europeans. The NAT2 rs1041983, NAT2 rs1799931, CYP2C19 rs4986893, CYP2C19 rs3758581, and CYP2B6 rs3745274 variants demonstrated significantly higher MAFs than in Europeans but not significantly different from South Asians. Conclusion This preliminary study identifies variants in NAT2 , UGT1A1 , CYP2B6 , and CYP2C19 genes relevant to the metabolism of anti-TB drugs, antiretrovirals, and voriconazole among Sri Lankans. Several variants, including CYP2C19 rs12769205 and rs4244285, showed higher MAFs, particularly in comparison to European populations, indicating potential differences in drug response. However, the nature of the study limits the ability to explore clinical correlations with the genotypes, therefore further research focusing on clinical correlation and functional validation is required. Anti-infective medicines are crucial for treating infections, but improper dosing can cause toxicity, resistance and treatment failure. Pharmacogenomics can address genetic variations affecting drug efficacy and safety. Despite the high burden of diseases like TB and HIV in Sri Lanka and South Asia, pharmacogenomic data for these populations are limited. This study aims to fill this gap by investigating pharmacogenomic variants in a South Asian population from Sri Lankan. Pharmacogenomic data on anti-infective medicines were obtained from the PharmGKB database, selecting variants with evidence levels 1 A, 1B, 2 A, and 2B. Sri Lankan genetic data were sourced from an anonymized database of 670 Sri Lankans maintained by the Centre for Genetics and Genomics, Faculty of Medicine, University of Colombo. MAFs were compared between Sri Lankan sub-populations and global data from gnomAD, with statistical significance set at p < 0.05. MAFs of NAT2 gene rs1041983 and rs1799931 variants were, 43.7% (95%CI:41.1-46.4), 7.3% (95%CI:6.0-8.8), respectively. The UGT1A1 rs4148323 variant had a MAF of 3.5% (95%CI:2.6-4.6). In the CYP2B6 gene, 109 individuals were homozygous for the rs3745274 (poor metaboliser) variant, with a MAF of 39.6% (95%CI:37.0-42.3), while the rs34097093 and rs28399499 variants had no individuals homozygous for the variant (MAF: 0.2% [95%CI:0-0.5] (poor/intermediate metaboliser), and 0.1% [95%CI:0-0.4] (poor/intermediate metaboliser), respectively). The MAFs of the CYP2C19 rs12769205 (poor/intermediate metaboliser), rs4244285 (poor/intermediate metaboliser), rs3758581 (poor/intermediate metaboliser), and rs4986893 (poor/intermediate metaboliser) variants were 41.9% (95%CI:39.3-44.6), 41.9% (95%CI:39.2-44.7), 9.7% (95%CI:8.2-11.4), and 0.5% [(95%CI:0.2-1.1), respectively. Most variants showed significant differences compared to global populations, with some exhibiting higher frequencies, particularly when compared to Europeans. CYP2C19 rs12769205 and rs4244285 exhibited higher MAFs in Sri Lankans compared to both other South Asians and Europeans. The NAT2 rs1041983, NAT2 rs1799931, CYP2C19 rs4986893, CYP2C19 rs3758581, and CYP2B6 rs3745274 variants demonstrated significantly higher MAFs than in Europeans but not significantly different from South Asians. This preliminary study identifies variants in NAT2, UGT1A1, CYP2B6, and CYP2C19 genes relevant to the metabolism of anti-TB drugs, antiretrovirals, and voriconazole among Sri Lankans. Several variants, including CYP2C19 rs12769205 and rs4244285, showed higher MAFs, particularly in comparison to European populations, indicating potential differences in drug response. However, the nature of the study limits the ability to explore clinical correlations with the genotypes, therefore further research focusing on clinical correlation and functional validation is required. Background Anti-infective medicines are crucial for treating infections, but improper dosing can cause toxicity, resistance and treatment failure. Pharmacogenomics can address genetic variations affecting drug efficacy and safety. Despite the high burden of diseases like TB and HIV in Sri Lanka and South Asia, pharmacogenomic data for these populations are limited. This study aims to fill this gap by investigating pharmacogenomic variants in a South Asian population from Sri Lankan. Methods Pharmacogenomic data on anti-infective medicines were obtained from the PharmGKB database, selecting variants with evidence levels 1 A, 1B, 2 A, and 2B. Sri Lankan genetic data were sourced from an anonymized database of 670 Sri Lankans maintained by the Centre for Genetics and Genomics, Faculty of Medicine, University of Colombo. MAFs were compared between Sri Lankan sub-populations and global data from gnomAD, with statistical significance set at p < 0.05. Results MAFs of NAT2 gene rs1041983 and rs1799931 variants were, 43.7% (95%CI:41.1-46.4), 7.3% (95%CI:6.0-8.8), respectively. The UGT1A1 rs4148323 variant had a MAF of 3.5% (95%CI:2.6-4.6). In the CYP2B6 gene, 109 individuals were homozygous for the rs3745274 (poor metaboliser) variant, with a MAF of 39.6% (95%CI:37.0-42.3), while the rs34097093 and rs28399499 variants had no individuals homozygous for the variant (MAF: 0.2% [95%CI:0-0.5] (poor/intermediate metaboliser), and 0.1% [95%CI:0-0.4] (poor/intermediate metaboliser), respectively). The MAFs of the CYP2C19 rs12769205 (poor/intermediate metaboliser), rs4244285 (poor/intermediate metaboliser), rs3758581 (poor/intermediate metaboliser), and rs4986893 (poor/intermediate metaboliser) variants were 41.9% (95%CI:39.3-44.6), 41.9% (95%CI:39.2-44.7), 9.7% (95%CI:8.2-11.4), and 0.5% [(95%CI:0.2-1.1), respectively. Most variants showed significant differences compared to global populations, with some exhibiting higher frequencies, particularly when compared to Europeans. CYP2C19 rs12769205 and rs4244285 exhibited higher MAFs in Sri Lankans compared to both other South Asians and Europeans. The NAT2 rs1041983, NAT2 rs1799931, CYP2C19 rs4986893, CYP2C19 rs3758581, and CYP2B6 rs3745274 variants demonstrated significantly higher MAFs than in Europeans but not significantly different from South Asians. Conclusion This preliminary study identifies variants in NAT2, UGT1A1, CYP2B6, and CYP2C19 genes relevant to the metabolism of anti-TB drugs, antiretrovirals, and voriconazole among Sri Lankans. Several variants, including CYP2C19 rs12769205 and rs4244285, showed higher MAFs, particularly in comparison to European populations, indicating potential differences in drug response. However, the nature of the study limits the ability to explore clinical correlations with the genotypes, therefore further research focusing on clinical correlation and functional validation is required. Keywords: Anti-infectives, Sri Lanka, South Asia, Pharmacogenomics, Tuberculosis, HIV, Voriconazole Anti-infective medicines are crucial for treating infections, but improper dosing can cause toxicity, resistance and treatment failure. Pharmacogenomics can address genetic variations affecting drug efficacy and safety. Despite the high burden of diseases like TB and HIV in Sri Lanka and South Asia, pharmacogenomic data for these populations are limited. This study aims to fill this gap by investigating pharmacogenomic variants in a South Asian population from Sri Lankan.BACKGROUNDAnti-infective medicines are crucial for treating infections, but improper dosing can cause toxicity, resistance and treatment failure. Pharmacogenomics can address genetic variations affecting drug efficacy and safety. Despite the high burden of diseases like TB and HIV in Sri Lanka and South Asia, pharmacogenomic data for these populations are limited. This study aims to fill this gap by investigating pharmacogenomic variants in a South Asian population from Sri Lankan.Pharmacogenomic data on anti-infective medicines were obtained from the PharmGKB database, selecting variants with evidence levels 1 A, 1B, 2 A, and 2B. Sri Lankan genetic data were sourced from an anonymized database of 670 Sri Lankans maintained by the Centre for Genetics and Genomics, Faculty of Medicine, University of Colombo. MAFs were compared between Sri Lankan sub-populations and global data from gnomAD, with statistical significance set at p < 0.05.METHODSPharmacogenomic data on anti-infective medicines were obtained from the PharmGKB database, selecting variants with evidence levels 1 A, 1B, 2 A, and 2B. Sri Lankan genetic data were sourced from an anonymized database of 670 Sri Lankans maintained by the Centre for Genetics and Genomics, Faculty of Medicine, University of Colombo. MAFs were compared between Sri Lankan sub-populations and global data from gnomAD, with statistical significance set at p < 0.05.MAFs of NAT2 gene rs1041983 and rs1799931 variants were, 43.7% (95%CI:41.1-46.4), 7.3% (95%CI:6.0-8.8), respectively. The UGT1A1 rs4148323 variant had a MAF of 3.5% (95%CI:2.6-4.6). In the CYP2B6 gene, 109 individuals were homozygous for the rs3745274 (poor metaboliser) variant, with a MAF of 39.6% (95%CI:37.0-42.3), while the rs34097093 and rs28399499 variants had no individuals homozygous for the variant (MAF: 0.2% [95%CI:0-0.5] (poor/intermediate metaboliser), and 0.1% [95%CI:0-0.4] (poor/intermediate metaboliser), respectively). The MAFs of the CYP2C19 rs12769205 (poor/intermediate metaboliser), rs4244285 (poor/intermediate metaboliser), rs3758581 (poor/intermediate metaboliser), and rs4986893 (poor/intermediate metaboliser) variants were 41.9% (95%CI:39.3-44.6), 41.9% (95%CI:39.2-44.7), 9.7% (95%CI:8.2-11.4), and 0.5% [(95%CI:0.2-1.1), respectively. Most variants showed significant differences compared to global populations, with some exhibiting higher frequencies, particularly when compared to Europeans. CYP2C19 rs12769205 and rs4244285 exhibited higher MAFs in Sri Lankans compared to both other South Asians and Europeans. The NAT2 rs1041983, NAT2 rs1799931, CYP2C19 rs4986893, CYP2C19 rs3758581, and CYP2B6 rs3745274 variants demonstrated significantly higher MAFs than in Europeans but not significantly different from South Asians.RESULTSMAFs of NAT2 gene rs1041983 and rs1799931 variants were, 43.7% (95%CI:41.1-46.4), 7.3% (95%CI:6.0-8.8), respectively. The UGT1A1 rs4148323 variant had a MAF of 3.5% (95%CI:2.6-4.6). In the CYP2B6 gene, 109 individuals were homozygous for the rs3745274 (poor metaboliser) variant, with a MAF of 39.6% (95%CI:37.0-42.3), while the rs34097093 and rs28399499 variants had no individuals homozygous for the variant (MAF: 0.2% [95%CI:0-0.5] (poor/intermediate metaboliser), and 0.1% [95%CI:0-0.4] (poor/intermediate metaboliser), respectively). The MAFs of the CYP2C19 rs12769205 (poor/intermediate metaboliser), rs4244285 (poor/intermediate metaboliser), rs3758581 (poor/intermediate metaboliser), and rs4986893 (poor/intermediate metaboliser) variants were 41.9% (95%CI:39.3-44.6), 41.9% (95%CI:39.2-44.7), 9.7% (95%CI:8.2-11.4), and 0.5% [(95%CI:0.2-1.1), respectively. Most variants showed significant differences compared to global populations, with some exhibiting higher frequencies, particularly when compared to Europeans. CYP2C19 rs12769205 and rs4244285 exhibited higher MAFs in Sri Lankans compared to both other South Asians and Europeans. The NAT2 rs1041983, NAT2 rs1799931, CYP2C19 rs4986893, CYP2C19 rs3758581, and CYP2B6 rs3745274 variants demonstrated significantly higher MAFs than in Europeans but not significantly different from South Asians.This preliminary study identifies variants in NAT2, UGT1A1, CYP2B6, and CYP2C19 genes relevant to the metabolism of anti-TB drugs, antiretrovirals, and voriconazole among Sri Lankans. Several variants, including CYP2C19 rs12769205 and rs4244285, showed higher MAFs, particularly in comparison to European populations, indicating potential differences in drug response. However, the nature of the study limits the ability to explore clinical correlations with the genotypes, therefore further research focusing on clinical correlation and functional validation is required.CONCLUSIONThis preliminary study identifies variants in NAT2, UGT1A1, CYP2B6, and CYP2C19 genes relevant to the metabolism of anti-TB drugs, antiretrovirals, and voriconazole among Sri Lankans. Several variants, including CYP2C19 rs12769205 and rs4244285, showed higher MAFs, particularly in comparison to European populations, indicating potential differences in drug response. However, the nature of the study limits the ability to explore clinical correlations with the genotypes, therefore further research focusing on clinical correlation and functional validation is required. Anti-infective medicines are crucial for treating infections, but improper dosing can cause toxicity, resistance and treatment failure. Pharmacogenomics can address genetic variations affecting drug efficacy and safety. Despite the high burden of diseases like TB and HIV in Sri Lanka and South Asia, pharmacogenomic data for these populations are limited. This study aims to fill this gap by investigating pharmacogenomic variants in a South Asian population from Sri Lankan. Pharmacogenomic data on anti-infective medicines were obtained from the PharmGKB database, selecting variants with evidence levels 1 A, 1B, 2 A, and 2B. Sri Lankan genetic data were sourced from an anonymized database of 670 Sri Lankans maintained by the Centre for Genetics and Genomics, Faculty of Medicine, University of Colombo. MAFs were compared between Sri Lankan sub-populations and global data from gnomAD, with statistical significance set at p < 0.05. MAFs of NAT2 gene rs1041983 and rs1799931 variants were, 43.7% (95%CI:41.1-46.4), 7.3% (95%CI:6.0-8.8), respectively. The UGT1A1 rs4148323 variant had a MAF of 3.5% (95%CI:2.6-4.6). In the CYP2B6 gene, 109 individuals were homozygous for the rs3745274 (poor metaboliser) variant, with a MAF of 39.6% (95%CI:37.0-42.3), while the rs34097093 and rs28399499 variants had no individuals homozygous for the variant (MAF: 0.2% [95%CI:0-0.5] (poor/intermediate metaboliser), and 0.1% [95%CI:0-0.4] (poor/intermediate metaboliser), respectively). The MAFs of the CYP2C19 rs12769205 (poor/intermediate metaboliser), rs4244285 (poor/intermediate metaboliser), rs3758581 (poor/intermediate metaboliser), and rs4986893 (poor/intermediate metaboliser) variants were 41.9% (95%CI:39.3-44.6), 41.9% (95%CI:39.2-44.7), 9.7% (95%CI:8.2-11.4), and 0.5% [(95%CI:0.2-1.1), respectively. Most variants showed significant differences compared to global populations, with some exhibiting higher frequencies, particularly when compared to Europeans. CYP2C19 rs12769205 and rs4244285 exhibited higher MAFs in Sri Lankans compared to both other South Asians and Europeans. The NAT2 rs1041983, NAT2 rs1799931, CYP2C19 rs4986893, CYP2C19 rs3758581, and CYP2B6 rs3745274 variants demonstrated significantly higher MAFs than in Europeans but not significantly different from South Asians. This preliminary study identifies variants in NAT2, UGT1A1, CYP2B6, and CYP2C19 genes relevant to the metabolism of anti-TB drugs, antiretrovirals, and voriconazole among Sri Lankans. Several variants, including CYP2C19 rs12769205 and rs4244285, showed higher MAFs, particularly in comparison to European populations, indicating potential differences in drug response. However, the nature of the study limits the ability to explore clinical correlations with the genotypes, therefore further research focusing on clinical correlation and functional validation is required.
ArticleNumber	153
Audience	Academic
Author	Bhagya Hendalage, D. P. Sirisena, Nirmala Dissanayake, Vajira H. W. Ranasinghe, Priyanga Jeyapragasam, Hajanthy
Author_xml	– sequence: 1 givenname: Priyanga orcidid: 0000-0002-1522-9276 surname: Ranasinghe fullname: Ranasinghe, Priyanga email: priyanga@pharm.cmb.ac.lk organization: Department of Pharmacology, Faculty of Medicine, University of Colombo – sequence: 2 givenname: Hajanthy orcidid: 0009-0002-0802-4712 surname: Jeyapragasam fullname: Jeyapragasam, Hajanthy organization: Department of Pharmacology, Faculty of Medicine, University of Colombo – sequence: 3 givenname: Nirmala orcidid: 0000-0003-0994-6954 surname: Sirisena fullname: Sirisena, Nirmala organization: Department of Anatomy, Genetics and Biomedical Informatics, Faculty of Medicine, University of Colombo – sequence: 4 givenname: D. P. orcidid: 0009-0006-6228-6333 surname: Bhagya Hendalage fullname: Bhagya Hendalage, D. P. organization: Department of Anatomy, Genetics and Biomedical Informatics, Faculty of Medicine, University of Colombo – sequence: 5 givenname: Vajira H. W. orcidid: 0000-0002-3264-6856 surname: Dissanayake fullname: Dissanayake, Vajira H. W. organization: Department of Anatomy, Genetics and Biomedical Informatics, Faculty of Medicine, University of Colombo
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/39893405$$D View this record in MEDLINE/PubMed
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CitedBy_id	crossref_primary_10_1016_j_diagmicrobio_2025_117005
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Keywords	Anti-infectives Tuberculosis HIV Sri Lanka Voriconazole South Asia Pharmacogenomics
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Snippet	Background Anti-infective medicines are crucial for treating infections, but improper dosing can cause toxicity, resistance and treatment failure.... Anti-infective medicines are crucial for treating infections, but improper dosing can cause toxicity, resistance and treatment failure. Pharmacogenomics can... Background Anti-infective medicines are crucial for treating infections, but improper dosing can cause toxicity, resistance and treatment failure.... Abstract Background Anti-infective medicines are crucial for treating infections, but improper dosing can cause toxicity, resistance and treatment failure....
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SubjectTerms	Adult Anti-infective agents Anti-Infective Agents - adverse effects Anti-Infective Agents - pharmacology Anti-Infective Agents - therapeutic use Anti-infectives Arylamine N-Acetyltransferase - genetics Dosage and administration Female Genetic aspects Genetic Variation HIV Humans Infectious Diseases Internal Medicine Male Medical Microbiology Medicine Medicine & Public Health Middle Aged Parasitology Pharmacogenetics Pharmacogenomic Variants Pharmacogenomics Pharmacology, Experimental Physiological aspects Polymorphism, Single Nucleotide South Asia South Asian People - genetics Sri Lanka Tropical Medicine Tuberculosis
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Title	Pharmacogenomic profiling of variants affecting efficacy and toxicity of anti-infective medicines in a south Asian population from Sri Lanka
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