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The association between the NAT2 genetic polymorphisms and risk of DILI during anti-TB treatment: a systematic review and meta-analysis.

ABSTRACT: AIMS:The aim of this study is to evaluate the potential association between N-acetyltransferase type 2 (NAT2) polymorphisms and drug-induced liver injury during anti-TB treatment (AT-DILI). METHODS:We conducted a systematic review and performed a meta-analysis to clarify the role of NAT2 polymorphism in AT-DILI. PubMed, Medline and EMBASE databases were searched for studies published in English to December 31, 2017, on the association between the NAT2 polymorphism and AT-DILI risk. Outcomes were pooled with random-effects meta-analysis. Details were registered in the PROSPERO register (number: CRD42016051722). RESULTS:Thirty-seven studies involving 1527 cases and 7184 controls were included in this meta-analysis. The overall odds ratio (OR) of AT-DILI associated with NAT2 slow acetylator phenotype was 3.15 (95% CI 2.58-3.84, I2 = 51.3%, P = 0.000). The OR varied between different ethnic populations, ranging from 6.42 (95% CI 2.41-17.10, I2 = 2.3%) for the West Asian population to 2.32 (95% CI 0.58-9.24, I2 = 80.3%) for the European population. Within the slow NAT2 genotype, variation was also observed; NAT2*6/*7 was associated with the highest risk of AT-DILI (OR = 1.68, 95% CI 1.09-2.59) compared to the other slow NAT2 acetylators combined. CONCLUSIONS:NAT2 slow acetylation was observed to increase the risk of AT-DILI in tuberculosis patients. Our results support the hypothesis that the slow NAT2 genotype is a risk factor for AT-DILI.

SUBMITTER: Zhang M

PROVIDER: S-EPMC6256008 | biostudies-other | 2018 Dec

REPOSITORIES: biostudies-other

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The association between the NAT2 genetic polymorphisms and risk of DILI during anti-TB treatment: a systematic review and meta-analysis.

Zhang Min M Wang Shuqiang S Wilffert Bob B Tong Rongsheng R van Soolingen Dick D van den Hof Susan S Alffenaar Jan-Willem JW

British journal of clinical pharmacology 20181003 12

<h4>Aims</h4>The aim of this study is to evaluate the potential association between N-acetyltransferase type 2 (NAT2) polymorphisms and drug-induced liver injury during anti-TB treatment (AT-DILI).<h4>Methods</h4>We conducted a systematic review and performed a meta-analysis to clarify the role of NAT2 polymorphism in AT-DILI. PubMed, Medline and EMBASE databases were searched for studies published in English to December 31, 2017, on the association between the NAT2 polymorphism and AT-DILI risk ...[more]

PMID: 30047605

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Project description:BACKGROUND:Asthma is a common complex chronic, inflammatory polygenic disease with heterogeneous manifestations, affecting individuals of all age groups and posing an immense burden on healthcare resources. A number of studies have identified the association between a disintegrin and metalloprotease 33 (ADAM33) polymorphisms and asthma risk, however, the results still remain inconclusive. The objective of the present study was to identify the effect of ADAM33 variants in asthma susceptibility. METHODS:Eligible case-control studies published between January 2000 and June 2018 was searched and retrieved from online electronic databases. The odds ratio (OR) with its 95% confidence interval (CI) was employed to calculate the effect. RESULTS:A total of 63 case-control studies were finally screened out, including 13,280 asthma patients and 13,340 controls. Eleven SNPs of ADAM33 gene were identified. Our results detected a significant association between ADAM33 T2, Q1, F?+?1 and AA genotype of T?+?1 polymorphisms and asthma risk in total population. Subgroup analysis by ethnicities showed that the alleles and genotypes of T2, Q1 and F?+?1 polymorphisms were associated with asthma susceptibility among Asian populations, while V4 polymorphism was associated with asthma among Caucasian populations. Subgroup analysis by ages showed that T2, F?+?1 and ST?+?4 polymorphisms were associated with childhood asthma, while Q1 and V4 polymorphisms were associated with asthma risk in adults. Subgroup analysis by asthma severity showed that only the G allele of ADAM33 T1 polymorphism was associated with the severity of asthma when compared with the controls. In addition, T2, Q1 and F?+?1 polymorphisms of ADAM33 were significantly associated with increased the asthma risk in Chinese asthma patients. CONCLUSIONS:Our results found that T2, Q1 and F?+?1 polymorphisms of ADAM33 gene might contribute to asthma risk. Future well-designed case-control studies with large population and more ethnicities are still needed to estimate the association.

Dataset Information

The association between the NAT2 genetic polymorphisms and risk of DILI during anti-TB treatment: a systematic review and meta-analysis.

Publications

The association between the NAT2 genetic polymorphisms and risk of DILI during anti-TB treatment: a systematic review and meta-analysis.

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