Allelic and genotypic frequencies of NAT2, CYP2E1, and AADAC genes in a cohort of Peruvian tuberculosis patients

Levano, Kelly S.; Jaramillo‐Valverde, Luis; Tarazona, David; Sánchez, Cesar; Capristano, Silvia; Vasquez-Loarte, Tania; Solari, Lely; Mendoza‐Ticona, Alberto; Soto, Alonso; Rojas, Christian; Zegarra-Chapoñán, Roberto; Guio, Heinner

doi:10.1002/mgg3.1764

Cited by 9 publications

(4 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In one of our studies, we researched the presence of adverse reactions during anti-tuberculosis treatment in the Peruvian population. Our results suggest that 30% of the Peruvian populations are associated with the slow metabolism of isoniazid 29 . We also identified haplotypes with divergent associations with drug-induced liver injury (DILI), based on the mestizo or native Peruvian population.…”

Section: Introductionmentioning

confidence: 67%

The Peruvian Genome Project: expanding the global pool of genome diversity from South America

Guio,

Caceres,

Sanchez

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

The process of inhabiting the Americas by ancestral native American populations involved many individuals settling in the Peruvian Andes and Amazonian regions. Due to Latin American countries representing less than 1% of the human genome data available in public reference databases, the evolution and migration processes involved in adapting to this unique geography have not yet been fully explained. The Peruvian Genome Project is an initiative first of its kind, started in 2011, to address the underrepresentation of genomic data from native South American populations. This project has collected to date 1,149 samples from 17 traditional native and 13 mestizo (mixed of native, African, and European ancestry) communities. Currently, 150 whole genomes and 873 array-genotyped individuals have been sequenced from across the geography of Western South America, including coastal, Andes, and Amazonian regions. We discovered 1.6 million novel genetic variants with varying frequencies, indicative of local environmental adaptations and population drift. These novel variants allow us to infer local evolutionary traits and population-specific allele frequencies for people living at different altitudes, as well as varying adaptations to pathogens and living conditions. The Peruvian Genome Project is the result of more than a decade of work in sample selection, logistics, and approved regulatory community engagement, designed to enhance the human genome pool of diversity of native Americans. The data collected here enable the targeted characterization of endemic diseases, trait adaptations, and new variants of clinical significance in South America. The Peruvian Genome Project represents a step forward in international and multidisciplinary efforts to make precision medicine more inclusive and accessible for underrepresented communities in Latin America, offering significant potential for drug development and diagnostics in a neglected continent.

show abstract

Section: Introductionmentioning

confidence: 67%

The Peruvian Genome Project: expanding the global pool of genome diversity from South America

Guio,

Caceres,

Sanchez

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Two mother studies are reported, the first carried out by researchers from the National Institute of Health (NIH) through a cross‐sectional study with the objective of describing and determining the frequency of the NAT2 , CYP2E1 and AADAC genotypes, related to the metabolism of INH and rifampicin (RIF) 19 in the Lima population. The second was carried out by researchers from the Brazilian EPIGEN Consortium through a cohort study to address the underrepresentation of non‐European individuals in studies of human genome diversity, reporting SNPs of clinical importance in the Brazilian and Latin American population 20 …”

Section: Methodsmentioning

confidence: 99%

“…For the INS original study samples, 200 microliters of peripheral blood were used to extract DNA using the QIAamp DNA Blood Mini Kit (Qiagen). Specific primers for the NAT2 fragment were designed and CYP2E1 fragments 19 were PCR amplified using the Taq PCR Master Mix Kit (Qiagen). PCR products were purified using the QIAquick Gel Extraction kit (Qiagen).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacogenetic variability of tuberculosis biomarkers in native and mestizo Peruvian populations

Jaramillo‐Valverde,

Levano,

Tarazona

et al. 2024

Pharmacology Res & Perspec

Self Cite

View full text Add to dashboard Cite

In Peru, 29 292 people were diagnosed with tuberculosis in 2022. Although tuberculosis treatments are effective, 3.4%–13% are associated with significant adverse drug reactions, with drug‐induced liver injury (DILI) considered the most predominant. Among the first‐line antituberculosis drugs, isoniazid is the main drug responsible for the appearance of DILI. In liver, isoniazid (INH) is metabolized by N‐acetyltransferase‐2 (NAT2) and cytochrome P450 2E1 (CYP2E1). Limited information exists on genetic risk factors associated with the presence of DILI to antituberculosis drugs in Latin America, and even less is known about these factors in the native and mestizo Peruvian population. The aim of this study was to determine the prevalence of NAT2 and CYP2E1 genotypes in native and mestizo population. An analytical cross‐sectional analysis was performed using genetic data from mestizo population in Lima and native participants from south of Peru. NAT2 metabolizer was determined as fast, intermediate and slow, and CYP2E1 genotypes were classified as c1/c1, c1/c2 and c2/c2, from molecular tests and bioinformatic analyses. Of the 472 participants, 36 and 6 NAT2 haplotypes were identified in the mestizo and native population, respectively. In mestizo population, the most frequent NAT2*5B and NAT2*7B haplotypes were associated with DILI risk; while in natives, NAT2*5G and NAT2*13A haplotypes were associated with decreased risk of DILI. For CYP2E1, c1/c1 and c1/c2 genotypes are the most frequent in natives and mestizos, respectively. The linkage disequilibrium of NAT2 single nucleotide polymorphisms (SNPs) was estimated, detecting a block between all SNPs natives. In addition, a block between rs1801280 and rs1799929 for NAT2 was detected in mestizos. Despite the limitations of a secondary study, it was possible to report associations between NAT2 and CYP2E alleles with Peruvian native and mestizo by prevalence ratios. The results of this study will help the development of new therapeutic strategies for a Tuberculosis efficient control between populations.

show abstract