N-acetyltransferase and cytochrome P450 2E1 gene polymorphisms and susceptibility to antituberculosis drug hepatotoxicity in an Indian population.

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dc.contributor.authorMISHRA, SWAPNIL
dc.contributor.authorDASCHAKRABORTY, SUNILBARAN
dc.contributor.authorSHUKLA, PALLAVI
dc.contributor.authorKAPOOR, PRERNA
dc.contributor.authorAGGARWAL, RAKESH
dc.date.accessioned2015-02-26T04:14:00Z
dc.date.available2015-02-26T04:14:00Z
dc.date.issued2013-09
dc.description.abstractBackground. Antituberculosis drug hepatotoxicity (ATDH) is common in India. Isoniazid, a constituent of most antituberculosis drug regimens, is metabolized by N-acetyltransferase (NAT2) and cytochrome P450 2E1 (CYP2E1) enzymes. We therefore studied the association of some single-nucleotide polymorphisms (SNPs) in these enzyme genes with ATDH. Methods. Allelic and genotypic frequencies at three SNP loci in the NAT2 gene (rs1799929, rs1799930 and rs1799931) and one locus (rs2031920) in the CYP2E1 gene were studied using restriction fragment length polymorphism in 33 patients who developed ATDH following an isoniazidcontaining antituberculosis drug regimen and 173 healthy blood donors. After confirming adherence of the control data to the Hardy–Weinberg equilibrium model, genotype and allele frequencies in the two groups were compared. Results. For SNP rs1799930 in the NAT2 gene, 7 (21%), 21 (64%) and 5 (15%) patients, and 93 (54%), 62 (36%) and 18 (10%) controls had GG, GA and AA genotypes, respectively (p=0.003; odds ratio [OR] for GA v. GG=4.50 [95% CI 1.80–11.22] and for AA v. GG=3.69 [1.05–12.93]). Allele frequency for G nucleotides for this SNP was 0.53 among patients and 0.72 among controls (OR 2.24 [1.31–3.84], p=0.007). The allele and genotype frequencies of the other NAT2 SNPs and the CYP2E1 SNP showed no significant difference between cases and controls. All the 33 patients and 151 (87%) of 173 controls had mutant allele at one or more of the three NAT2 SNP loci (p=0.03). The presence of two or more mutant alleles, a marker of slow acetylator status, was more frequent in patients (23/33 [70%]) than in controls (73/173 [42%]; OR 3.23 [95% CI 1.45–7.19], p=0.004). Conclusion. In India, the risk of ATDH is increased in persons with ‘A’ allele at SNP rs1799930 in the NAT2 gene, but is not associated with rs2031920 polymorphism in the CYP2E1 gene.en_US
dc.identifier.citationMISHRA SWAPNIL, DASCHAKRABORTY SUNILBARAN, SHUKLA PALLAVI, KAPOOR PRERNA, AGGARWAL RAKESH. N-acetyltransferase and cytochrome P450 2E1 gene polymorphisms and susceptibility to antituberculosis drug hepatotoxicity in an Indian population. National Medical Journal of India. 2013 Sept-Oct ; 26 (5): 260-265.en_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/156381
dc.language.isoenen_US
dc.source.urihttps://nmji.in/archives/Volume-26/Issue-5/OA-I-26-5-2014.pdfen_US
dc.subject.meshAdult
dc.subject.meshAntitubercular Agents --adverse effects
dc.subject.meshArylamine N-Acetyltransferase --genetics
dc.subject.meshCase-Control Studies
dc.subject.meshCytochrome P-450 CYP2E1 --genetics
dc.subject.meshDrug-Induced Liver Injury --epidemiology
dc.subject.meshDrug-Induced Liver Injury --etiology
dc.subject.meshDrug-Induced Liver Injury --genetics
dc.subject.meshFemale
dc.subject.meshGene Frequency
dc.subject.meshGenetic Predisposition to Disease --genetics
dc.subject.meshGenotype
dc.subject.meshHumans
dc.subject.meshIndia
dc.subject.meshLiver Function Tests
dc.subject.meshMale
dc.subject.meshPoint Mutation
dc.subject.meshPolymerase Chain Reaction
dc.subject.meshPolymorphism, Restriction Fragment Length
dc.subject.meshPolymorphism, Single Nucleotide
dc.subject.meshProspective Studies
dc.subject.meshRisk
dc.titleN-acetyltransferase and cytochrome P450 2E1 gene polymorphisms and susceptibility to antituberculosis drug hepatotoxicity in an Indian population.en_US
dc.typeArticleen_US
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