Validation of PHASE for deriving N-acetyltransferase 2 haplotypes in the Western Cape mixed ancestry population

African Journal of Laboratory Medicine

Field Value
Title Validation of PHASE for deriving N-acetyltransferase 2 haplotypes in the Western Cape mixed ancestry population
Creator Swart, Celeste Meldau, Surita Centner, Chad M. Marais, Adrian D. Omar, Fierdoz
Subject Pathology; molecular NAT2; haplotyping; isoniazid; pathology; molecular
Description Background: There is a shortage of data on the accuracy of statistical methods for the prediction of N-acetyltransferase 2 (NAT2) haplotypes in the mixed ancestry population of the Western Cape.Objective: This study aimed to identify the NAT2 haplotypes and assess the accuracy of PHASE version 2.1.1 in assigning NAT2 haplotypes to a mixed ancestry population from the Western Cape.Methods: This study was conducted between 2013 and 2016. The NAT2 gene was amplified and sequenced from the DNA of 100 self-identified mixed ancestry participants. Haplotyping was performed by molecular and computational techniques. Agreement was assessed between the two techniques.Results: Haplotypes were assigned to 93 samples, of which 67 (72%) were ambiguous. Haplotype prediction by PHASE demonstrated 94.6% agreement (kappa 0.94, p 0.001) with those assigned using molecular techniques. Five haplotype combinations (from 10 chromosomes) were incorrectly predicted, four of which were flagged as uncertain by the PHASE software. Only one resulted in the assignment of an incorrect acetylation phenotype (intermediate to slow), although the software flagged this for further analysis. The most common haplotypes were NAT2*4 (28%) followed by NAT2*5B (27.4%), NAT2*6A (21.5%) and NAT2*12A (7.5%). Four rare single nucleotide variants (c.589CT, c.622TC, c.809TC and c.387CT) were detected.Conclusion: PHASE accurately predicted the phenotype in 92 of 93 samples (99%) from genotypic data in our mixed ancestry sample population, and is therefore a suitable alternative to molecular methods to individualise isoniazid therapy in this high burden tuberculosis setting.
Publisher AOSIS
Date 2020-12-17
Type info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion — Comparative
Format text/html application/epub+zip text/xml application/pdf
Identifier 10.4102/ajlm.v9i1.988
Source African Journal of Laboratory Medicine; Vol 9, No 1 (2020); 7 pages 2225-2010 2225-2002
Language eng
Coverage South Africa; Western Cape — Mixed ancestry population
Rights Copyright (c) 2020 Celeste Swart, Fierdoz Omar, Surita Meldau, Adrian David Marais