Association of genetic variants with anti-tuberculosis drug induced hepatotoxicity: A high resolution melting analysis
DSpace at IIT Bombay
View Archive InfoField | Value | |
Title |
Association of genetic variants with anti-tuberculosis drug induced hepatotoxicity: A high resolution melting analysis
|
|
Creator |
SINGH, M
GUPTA, VH AMARAPURKAR, DN JOSHI, JM BAIJAL, R RAMEGOWDA, PH AMARAPURKAR, AD WANGIKAR, PP |
|
Subject |
Tuberculosis
Drug induced hepatotoxicity High resolution melting Mutation screening SINGLE NUCLEOTIDE POLYMORPHISMS CYTOCHROME-P450 2E1 GENOTYPE N-ACETYLTRANSFERASE INDUCED HEPATITIS DNA SLC22A3 COHORT MODEL RISK NAT2 |
|
Description |
Background: Tuberculosis (TB) treatment remains a challenge owing to the high incidence of drug induced hepatotoxicity (DIH). Apart from environmental factors, single nucleotide polymorphisms (SNPs) in drug metabolizing enzymes (DMEs), nuclear receptors (NRs) and transporter proteins (TPs) contribute to DIH. In the present study, we report known and novel SNPs in a total of seven genes of DMEs, NRs and TPs with high resolution melting (HRM) technique. Methods: DNA samples of 185 TB patients of Western Indian population, of which 50 showed DIH, were analyzed. Grouping of the temperature-shifted difference plots obtained from the DNA melt curves enables identification of known and novel SNPs. Representative samples of each group were sequenced. Results: We report 18 novel SNPs, of which 3 are in 5 '-UTR, 14 in exonic and 1 in intronic region. Of the SNPs in exons, 7 non-synonymous, 3 synonymous and 4 deletion mutations were observed. Among the known SNPs, CYP2E1 wild-type, NAT2*5 mutant and NAT2*6 heterozygous genotypes were associated with DIH (p < 0.05). Among the novel SNPs, group 2 of SLCO1B1 showed a significant association (p < 0.05). Conclusions: While several SNPs showed borderline p values between 0.05 and 0.15, the confidence in association can be improved further by using larger data sets. (C) 2014 Elsevier B.V. All rights reserved.
|
|
Publisher |
ELSEVIER SCIENCE BV
|
|
Date |
2014-12-28T14:30:50Z
2014-12-28T14:30:50Z 2014 |
|
Type |
Article
|
|
Identifier |
INFECTION GENETICS AND EVOLUTION, 2342-48
1567-1348 1567-7257 http://dx.doi.org/10.1016/j.meegid.2014.01.027 http://dspace.library.iitb.ac.in/jspui/handle/100/16758 |
|
Language |
English
|
|