Allelic and genotypic frequencies of NAT2, CYP2E1, and AADAC genes in a cohort of Peruvian tuberculosis patients
Abstract Background We determined the frequency of genetic polymorphisms in three anti‐TB drug metabolic proteins previously reported: N‐acetyltransferase 2 (NAT2), cytochrome P450 2E1 (CYP2E1), and arylacetamide deacetylase (AADAC) within a Peruvian population in a cohort of TB patients. Methods We...
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Wiley
2021
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oai:doaj.org-article:deb03150ba3546dbb33987ff2a70f5442021-11-10T16:39:23ZAllelic and genotypic frequencies of NAT2, CYP2E1, and AADAC genes in a cohort of Peruvian tuberculosis patients2324-926910.1002/mgg3.1764https://doaj.org/article/deb03150ba3546dbb33987ff2a70f5442021-10-01T00:00:00Zhttps://doi.org/10.1002/mgg3.1764https://doaj.org/toc/2324-9269Abstract Background We determined the frequency of genetic polymorphisms in three anti‐TB drug metabolic proteins previously reported: N‐acetyltransferase 2 (NAT2), cytochrome P450 2E1 (CYP2E1), and arylacetamide deacetylase (AADAC) within a Peruvian population in a cohort of TB patients. Methods We genotyped SNPs rs1041983, rs1801280, rs1799929, rs1799930, rs1208, and rs1799931 for NAT2; rs3813867 and rs2031920 for CYP2E1; and rs1803155 for AADAC in 395 participants completed their antituberculosis treatment. Results Seventy‐four percent of the participants are carriers of slow metabolizer genotypes: NAT2*5, NAT2*6, and NAT2*7, which increase the sensitivity of INH at low doses and increase the risk of drug‐induced liver injuries. Sixty‐four percent are homozygous for the wild‐type CYP2E1*1A allele, which could increase the risk of hepatotoxicity. However, 16% had a NAT2 fast metabolizer phenotype which could increase the risk of acquiring resistance to INH, thereby increasing the risk of multidrug‐resistant (MDR) or treatment failure. The frequency of rs1803155 (AADAC*2 allele) was higher (99.9%) in Peruvians than in European American, African American, Japanese, and Korean populations. Conclusions This high prevalence of slow metabolizers for isoniazid in the Peruvian population should be further studied and considered to help individualize drug regimens, especially in countries with a great genetic diversity like Peru. These data will help the Peruvian National Tuberculosis Control Program develop new strategies for therapies.Kelly S. LevanoLuis Jaramillo‐ValverdeDavid D. TarazonaCesar SanchezSilvia CapristanoTania Vásquez‐LoarteLely SolariAlberto Mendoza‐TiconaAlonso SotoChristian RojasRoberto Zegarra‐ChapoñanHeinner GuioWileyarticleAADACCYP2E1NAT2tuberculosisGeneticsQH426-470ENMolecular Genetics & Genomic Medicine, Vol 9, Iss 10, Pp n/a-n/a (2021) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
AADAC CYP2E1 NAT2 tuberculosis Genetics QH426-470 |
| spellingShingle |
AADAC CYP2E1 NAT2 tuberculosis Genetics QH426-470 Kelly S. Levano Luis Jaramillo‐Valverde David D. Tarazona Cesar Sanchez Silvia Capristano Tania Vásquez‐Loarte Lely Solari Alberto Mendoza‐Ticona Alonso Soto Christian Rojas Roberto Zegarra‐Chapoñan Heinner Guio Allelic and genotypic frequencies of NAT2, CYP2E1, and AADAC genes in a cohort of Peruvian tuberculosis patients |
| description |
Abstract Background We determined the frequency of genetic polymorphisms in three anti‐TB drug metabolic proteins previously reported: N‐acetyltransferase 2 (NAT2), cytochrome P450 2E1 (CYP2E1), and arylacetamide deacetylase (AADAC) within a Peruvian population in a cohort of TB patients. Methods We genotyped SNPs rs1041983, rs1801280, rs1799929, rs1799930, rs1208, and rs1799931 for NAT2; rs3813867 and rs2031920 for CYP2E1; and rs1803155 for AADAC in 395 participants completed their antituberculosis treatment. Results Seventy‐four percent of the participants are carriers of slow metabolizer genotypes: NAT2*5, NAT2*6, and NAT2*7, which increase the sensitivity of INH at low doses and increase the risk of drug‐induced liver injuries. Sixty‐four percent are homozygous for the wild‐type CYP2E1*1A allele, which could increase the risk of hepatotoxicity. However, 16% had a NAT2 fast metabolizer phenotype which could increase the risk of acquiring resistance to INH, thereby increasing the risk of multidrug‐resistant (MDR) or treatment failure. The frequency of rs1803155 (AADAC*2 allele) was higher (99.9%) in Peruvians than in European American, African American, Japanese, and Korean populations. Conclusions This high prevalence of slow metabolizers for isoniazid in the Peruvian population should be further studied and considered to help individualize drug regimens, especially in countries with a great genetic diversity like Peru. These data will help the Peruvian National Tuberculosis Control Program develop new strategies for therapies. |
| format |
article |
| author |
Kelly S. Levano Luis Jaramillo‐Valverde David D. Tarazona Cesar Sanchez Silvia Capristano Tania Vásquez‐Loarte Lely Solari Alberto Mendoza‐Ticona Alonso Soto Christian Rojas Roberto Zegarra‐Chapoñan Heinner Guio |
| author_facet |
Kelly S. Levano Luis Jaramillo‐Valverde David D. Tarazona Cesar Sanchez Silvia Capristano Tania Vásquez‐Loarte Lely Solari Alberto Mendoza‐Ticona Alonso Soto Christian Rojas Roberto Zegarra‐Chapoñan Heinner Guio |
| author_sort |
Kelly S. Levano |
| title |
Allelic and genotypic frequencies of NAT2, CYP2E1, and AADAC genes in a cohort of Peruvian tuberculosis patients |
| title_short |
Allelic and genotypic frequencies of NAT2, CYP2E1, and AADAC genes in a cohort of Peruvian tuberculosis patients |
| title_full |
Allelic and genotypic frequencies of NAT2, CYP2E1, and AADAC genes in a cohort of Peruvian tuberculosis patients |
| title_fullStr |
Allelic and genotypic frequencies of NAT2, CYP2E1, and AADAC genes in a cohort of Peruvian tuberculosis patients |
| title_full_unstemmed |
Allelic and genotypic frequencies of NAT2, CYP2E1, and AADAC genes in a cohort of Peruvian tuberculosis patients |
| title_sort |
allelic and genotypic frequencies of nat2, cyp2e1, and aadac genes in a cohort of peruvian tuberculosis patients |
| publisher |
Wiley |
| publishDate |
2021 |
| url |
https://doaj.org/article/deb03150ba3546dbb33987ff2a70f544 |
| work_keys_str_mv |
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