AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treat...AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treated with anti-TB drugs including INH. The frequencies and distributions of single nucleotide polymorphisms, haplotypes, and diplotypes of NAT2 were determined by the PCR-restriction fragment length polymorphism method, and the results were compared between TB patients with and without adverse effect, using multivariate logistic regression analysis.RESULTS: Statistical analysis revealed that the frequency of a variant haplotype, NAT2*6A , was signifi cantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity [P = 0.001, odds ratio (OR) = 3.535]. By contrast, the frequency of a wild-type (major) haplotype, "NAT2*4", was signif icantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P < 0.001, OR = 0.265). There was no association between NAT2-haplotypes and skin rash or eosinophilia. CONCLUSION: The present study shows that NAT2 is one of the determinants of anti-TB drug-induced hepatotoxicity. Moreover, the haplotypes, NAT2*4 and NAT2*6A, are useful new biomarkers for predicting anti- TB drug-induced hepatotoxicity.展开更多
AIM: To study whether N-acetyltransferase 2 (NAT2) genotypes and phenotypes are associated with increased risk factor for gastric cancer in Omani patients and to study the clinico-pathological correlations and the ...AIM: To study whether N-acetyltransferase 2 (NAT2) genotypes and phenotypes are associated with increased risk factor for gastric cancer in Omani patients and to study the clinico-pathological correlations and the prognostic significance of NAT2. METHODS: Genomic DNA was extracted from peripheral blood of 100 gastric cancer patients and 100 control subjects. NAT2 genotyping was performed using DNA sequencing. The prognostic significance of NAT2 and other clinicopathological features was assessed by univariate and multivariate analyses. RESULTS: We observed no significant association between NAT2 genotypes and phenotypes and gastric cancer risk. The IVAT2 phenotype polymorphisms and gastric cancer risk predisposition were not modified by concomitant Hpylori infection and smoking. There was no significant association between NAT2 and clinicopathological features, and NAT2 had no independent prognostic significance. CONCLUSION: In the current study, NAT2 genotypes and phenotypes are not associated with gastric cancer risk predisposition. Moreover NAT2 phenotypes had no clinicopathological associations or prognostic significance.展开更多
基金by Grant-in-Aid for Scientif ic Research (Category B, No. 18390168) for K Tsukamoto by the Ministry of Education, Culture, Sports, Science and Technology of Japan
文摘AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treated with anti-TB drugs including INH. The frequencies and distributions of single nucleotide polymorphisms, haplotypes, and diplotypes of NAT2 were determined by the PCR-restriction fragment length polymorphism method, and the results were compared between TB patients with and without adverse effect, using multivariate logistic regression analysis.RESULTS: Statistical analysis revealed that the frequency of a variant haplotype, NAT2*6A , was signifi cantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity [P = 0.001, odds ratio (OR) = 3.535]. By contrast, the frequency of a wild-type (major) haplotype, "NAT2*4", was signif icantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P < 0.001, OR = 0.265). There was no association between NAT2-haplotypes and skin rash or eosinophilia. CONCLUSION: The present study shows that NAT2 is one of the determinants of anti-TB drug-induced hepatotoxicity. Moreover, the haplotypes, NAT2*4 and NAT2*6A, are useful new biomarkers for predicting anti- TB drug-induced hepatotoxicity.
文摘AIM: To study whether N-acetyltransferase 2 (NAT2) genotypes and phenotypes are associated with increased risk factor for gastric cancer in Omani patients and to study the clinico-pathological correlations and the prognostic significance of NAT2. METHODS: Genomic DNA was extracted from peripheral blood of 100 gastric cancer patients and 100 control subjects. NAT2 genotyping was performed using DNA sequencing. The prognostic significance of NAT2 and other clinicopathological features was assessed by univariate and multivariate analyses. RESULTS: We observed no significant association between NAT2 genotypes and phenotypes and gastric cancer risk. The IVAT2 phenotype polymorphisms and gastric cancer risk predisposition were not modified by concomitant Hpylori infection and smoking. There was no significant association between NAT2 and clinicopathological features, and NAT2 had no independent prognostic significance. CONCLUSION: In the current study, NAT2 genotypes and phenotypes are not associated with gastric cancer risk predisposition. Moreover NAT2 phenotypes had no clinicopathological associations or prognostic significance.