Capristano, S. | Search bioRxiv

bioRxiv2021

Allelic and Genotypic Frequencies of NAT2, CYP2E1 and AADAC genes in a cohort of Peruvian Tuberculosis Patients

BackgroundWe 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. We included 395 participants completed their anti-tuberculosis treatment. Results[~]74% 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. [~] 64% 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 in European American, African American, Japanese, and Korean populations. ConclusionsThis 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.

genetics↗

bioRxiv2017

The Evolutionary Genomic Dynamics of Peruvians Before, During, and After the Inca Empire

Native Americans from the Amazon, Andes, and coast regions of South America have a rich cultural heritage, but have been genetically understudied leading to gaps in our knowledge of their genomic architecture and demographic history. Here, we sequenced 150 high-coverage and genotyped 130 genomes from Native American and mestizo populations in Peru. A majority of our samples possess greater than 90% Native American ancestry and demographic modeling reveals, consistent with a rapid peopling model of the Americas, that most of Peru was peopled approximately 12,000 years ago. While the Native American populations possessed distinct ancestral divisions, the mestizo groups were admixtures of multiple Native American communities which occurred before and during the Inca Empire. The mestizo communities also show Spanish introgression only after Peruvian Independence. Thus, we present a detailed model of the evolutionary dynamics which impacted the genomes of modern day Peruvians.

genomics↗