Evidence map›Paper›PMID 30882558›Full record

ArticlePharmacogenetics and genomics2019

N-acetyltransferase 2 enzyme genotype-phenotype discordances in both HIV-negative and HIV-positive Nigerians.

Olayinka A Kotila, Olufunmilayo I Fawole, Olufunmilayo I Olopade, Adejumoke I Ayede, Adeyinka G Falusi, Chinedum P Babalola

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In one paragraph

Article in Pharmacogenetics and genomics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.5field-weighted citation impact, top 32% of its field
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 7 citations in OpenAlex.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

Olayinka A KotilaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy.
Olufunmilayo I FawoleDepartment of Epidemiology and Medical Statistics, Faculty of Public Health, College of Medicine, University of Ibadan, Oyo State, Nigeria.
Olufunmilayo I OlopadeDepartment of Hematology and Oncology, Biological Sciences Division, University of Chicago, Chicago, Illinois, USA.
Adejumoke I AyedeDepartment of Paediatrics, College of Medicine.
Adeyinka G FalusiGenetics and Bioethics Unit, Institute of Advanced Medical Research and Training (IMRAT).
Chinedum P BabalolaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy.
University of Ibadan · NGUniversity of Chicago · US

Funding

Medical Education Partnership Initiative in NigeriaR24TW008878 · FIC · COLLEGE OF MEDICINE, UNIVERSITY OF IBADAN · PI ADEWOLE, ISAAC F, OLALEYE, DAVID OLUFEMI · 2010 to 2015
$9.4M
Summer Program to Increase Heart, Lung, and Blood Biomedical ResearchR25HL096383 · NHLBI · UNIVERSITY OF CHICAGO · PI CHRISTOPHER O OLOPADE, William F Parker · 2009 to 2026
$2.1M
International Partnership for Interdisciplinary Research TrainingD43TW009112 · FIC · UNIVERSITY OF CHICAGO · PI OLOPADE, CHRISTOPHER O, OLOPADE, OLUFUNMILAYO F. · 2012 to 2016
$1.1M
FIC NIH HHS D43 TW009112FIC NIH HHS R24 TW008878NHLBI NIH HHS R25 HL096383
6 · The paper itself

Abstract

backgroundThe N-acetyltransferase 2 (NAT2) enzyme has been understudied in Nigerians including genotype-phenotype association studies.

objectiveThe aim of this study was NAT2 haplotype identification and genotype-phenotype investigations in HIV-positive and HIV-negative Nigerians. PATIENTS AND

methodsPhenotypes included self-reported sulphonamide hypersensitivity survey, experimental and computational NAT2 phenotyping. The NAT2 gene was amplified by PCR. Gene sequencing used ABI 3730 and Haploview 4.2 for haplotype reconstruction. Genotype-phenotype analyses used the χ P-value and odds ratio with a 95% confidence interval.

resultsSelf-reported sulphonamide hypersensitivity showed a prevalence of 3.1 and 12.4% in HIV-positive and HIV-negative Nigerians, respectively. NAT2 genetic variants 191G>A, 282C>T, 341T>C, 481C>T, 590G>A, 803A>G and 857G>A were not significantly different between both groups (odds ratio=0.87; 95% confidence interval: 0.54-1.38, P=0.55). Nine haplotypes: NAT2*4, NAT2*12A, NAT2*13A, NAT2*5B, NAT2*6A, NAT2*7B, NAT2*5C, NAT2*14B and NAT2*14A had frequencies more than 1%, whereas NAT2*12B had 1.1% in the HIV-positive and 0.4% in the HIV-negative group. Overall, slow acetylator haplotypes made up 68%. The NAT2*12 signature single-nucleotide polymorphism was in high linkage disequilibrium with signature single-nucleotide polymorphism for NAT2*13 (D'=0.97, r=0.61) and NAT2*5 (D'=0.98, r=0.64). Genotype-phenotype association analysis showed haplotypes NAT2*13A, NAT2*5C, NAT2*7B and NAT2*14A to be associated strongly with the slow metabolic phenotype (P=0.002, 0.029, 0.032 and 0.050, respectively). Computational phenotypes were similar, with 30.9, 66 and 3.1% for slow, intermediate and rapid acetylators, respectively, among HIV-positive Nigerians and 31.2, 66.3 and 2.5% among the HIV-negative group. Overall, slow phenotypes made up 31%.

conclusionNAT2 haplotype frequencies are similar in Nigerians, irrespective of HIV status, but genotype-phenotype discordances exist.

Indexed as

Arylamine N-AcetyltransferaseDrug HypersensitivityFemaleGenetic Association StudiesHaplotypesHIVHIV InfectionsHumansMaleMiddle AgedNigeriaSulfonamidesTrimethoprim, Sulfamethoxazole Drug CombinationArylamine N-AcetyltransferaseNAT2 protein, humanSulfonamidesTrimethoprim, Sulfamethoxazole Drug Combination

Identifiers

PMID30882558
PMCPMC6542708
OpenAlexW2924281575

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.