Meta-analysis of phenotype and genotype of NAT2 deficiency in Chinese populations

Xie, Hong‐Guang; Xu, Zhenhua; Ouyang, Dongsheng; Shu, Yan; Yang, Dongliang; Wang, Junsheng; Yan, Xiang‐Dong; Huang, Shiyang; Wang, Wei; Zhou, Hong‐Hao

doi:10.1097/00008571-199712000-00009

Cited by 50 publications

(22 citation statements)

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“…Only 10% RA phenotypes were found, whereas 50% are expected in a Caucasian population [13,16,18]. Even if NAT2 allelic distributions were consistent with those predicted by the Hardy-Weinberg equation, they were markedly different from those obtained in Asian populations [27,28,34]. Hence, it is likely that the heterogeneity of our population accounts for these differences as important genotype/ phenotype prevalences of SA variations occur in accordance to the ethnic group considered (Oriental, 10%; Caucasian, 50%; Egyptian, 80%) [13,16,35,36].…”

Section: Discussionmentioning

confidence: 63%

CYP2E1 genotype and isoniazid-induced hepatotoxicity in patients treated for latent tuberculosis

Vuilleumier

Rossier

Chiappe

et al. 2006

Eur J Clin Pharmacol

157

105

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Objective: To determine whether pharmacogenetic tests such as N-acetyltransferase 2 (NAT2) and cytochrome P450 2E1 (CYP2E1) genotyping are useful in identifying patients prone to antituberculosis drug-induced hepatotoxicity in a cosmopolite population. Methods: In a prospective study we genotyped 89 patients treated with isoniazid (INH) for latent tuberculosis. INH-induced hepatitis (INH-H) or elevated liver enzymes including hepatitis (INH-ELE) was diagnosed based on the clinical diagnostic scale (CDS) designed for routine clinical practice. NAT2 genotypes were assessed by fluorescence resonance energy transfer probe after PCR analysis, and CYP2E1 genotypes were determined by PCR with restriction fragment length polymorphism analysis. Results: Twenty-six patients (29%) had INH-ELE, while eight (9%) presented with INH-H leading to INH treatment interruption. We report no significant influence of NAT2 polymorphism, but we did find a significant association between the CYP2E1 *1A/*1A genotype and INH-ELE (OR: 3.4; 95% CI:1.1-12; p=0.02) and a non significant trend for INH-H (OR: 5.9; 95% CI: 0.69-270; p=0.13) compared with other CYP2E1 genotypes. This test for predicting INH-ELE had a positive predictive value (PPV) of 39% (95% CI: 26-54%) and a negative predictive value (NPV) of 84% (95% CI: 69-94%). Conclusion:The genotyping of CYP2E1 polymorphisms may be a useful predictive tool in the common setting of a highly heterogeneous population for predicting isoniazidinduced hepatic toxicity. Larger prospective randomized trials are needed to confirm these results.

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Section: Discussionmentioning

confidence: 63%

CYP2E1 genotype and isoniazid-induced hepatotoxicity in patients treated for latent tuberculosis

Vuilleumier

Rossier

Chiappe

et al. 2006

Eur J Clin Pharmacol

157

105

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“…These and haplotype #7B with the mutation at site 857 explained 95% of the Kyrgyz variants. The haplotype #5B occurred with a higher frequency in Caucasians and with a lower frequency in the Kyrgyz from Central Asia but was rare in East Asians and Amerindians (12)(13)(14)(15)(16)(17).…”

Section: Discussionmentioning

confidence: 99%

“…We also found a lower frequency of predicted slow acetylators in Kyrgyz in comparison with Romanians. In Chinese, there is an even lower fraction of slow acetylators (14,21). Slow acetylators can be underestimated when only a few SNPs are used to predict the phenotype (10).…”

Section: Discussionmentioning

confidence: 99%

Variation of theN-Acetyltransferase 2Gene in a Romanian and a Kyrgyz Population

Rabstein

Unfried²,

Ranft³

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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As part of a project on environmental disasters in minority populations, this study aimed to evaluate differences in the sequence of N-acetyltransferase 2 (NAT2) as a metabolic susceptibility gene in yet unexplored ethnicities. Eight single nucleotide polymorphisms (SNP) in the NAT2 coding region and a variant in the 3V flanking region were analyzed in 290 unrelated Kyrgyz and 140 unrelated Romanians by SNP-specific PCR analysis. The variants 341C, 481T, and 803G were less and 857A more prevalent in Kyrgyz (P < 0.0001). The variant at site 857 indicates Asian descent. 282C>T and 590G>A showed no significant variation by ethnicity. 364G>A and 411A>T turned out to be monomorphic. Database comparisons of the NAT2 minor allele frequencies support that Romanians belong to Caucasians and Kyrgyz are in between Caucasians and East Asians. The distributions of predicted haplotypes differed significantly between the two ethnicities where the Kyrgyz showed a higher genetic diversity. The haplotype without mutations was more common in Kyrgyz (40.1% in Kyrgyz, 29.3% in Romanians). Accordingly, the imputed slow acetylator phenotype was less prevalent in Kyrgyz (35.2% versus 51.4% in Romanians). We found pronounced ethnic differences in NAT2 genotypes with yet unknown effect on the health risks for environmental or occupational exposures in minority populations. (Cancer Epidemiol Biomarkers Prev 2006;15(1):138 -41)

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“…In Caucasians, most of the fast acetylators are heterozygotes for slow and fast alleles, whereas individuals homozygous for fast alleles (e.g., NAT2*4/*4) comprise ϳ5% of the population (Cascorbi et al, 1995;Gross et al, 1999). In contrast, ϳ30% of Chinese individuals are homozygous for rapid alleles, 45% are heterozygotes, and 25% are homozygotes for slow alleles (Xie et al, 1997).…”

Section: A Acetyltransferasementioning

confidence: 96%