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
Determining how function evolves following gene duplication is necessary for understanding gene expansion.Transcription factors(TFs)are a class of proteins that regulate gene expression by binding to specific cis-acti...Determining how function evolves following gene duplication is necessary for understanding gene expansion.Transcription factors(TFs)are a class of proteins that regulate gene expression by binding to specific cis-acting elements in the promoters of target genes,subsequently activating or repressing their transcription.In the present study,we systematically examined the functional diversification of the NAC transcription factor(NAC-TFs)family by analyzing their chromosomal location,structure,phylogeny,and expression pattern in Gossypium raimondii(Gr)and G.arboreum(Ga).The 145 and 141 NAC genes identified in the Gr and Ga genomes,respectively,were annotated and divided into 18 subfamilies,which showed distinct divergence in gene structure and expression patterns during fiber development.In addition,when the functional parameters were examined,clear divergence was observed within tandem clusters,which suggested that subfunctionalization had occurred among duplicate genes.The expression patterns of homologous gene pairs also changed,suggestive of the diversification of gene function during the evolution of diploid cotton.These findings provide insights into the mechanisms underlying the functional differentiation of duplicated NAC-TFs genes in two diploid cotton species.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.
基金the National High Technology Research and Development Program of China (2013AA102601)the National Natural Science Foundation of China (31471538)
文摘Determining how function evolves following gene duplication is necessary for understanding gene expansion.Transcription factors(TFs)are a class of proteins that regulate gene expression by binding to specific cis-acting elements in the promoters of target genes,subsequently activating or repressing their transcription.In the present study,we systematically examined the functional diversification of the NAC transcription factor(NAC-TFs)family by analyzing their chromosomal location,structure,phylogeny,and expression pattern in Gossypium raimondii(Gr)and G.arboreum(Ga).The 145 and 141 NAC genes identified in the Gr and Ga genomes,respectively,were annotated and divided into 18 subfamilies,which showed distinct divergence in gene structure and expression patterns during fiber development.In addition,when the functional parameters were examined,clear divergence was observed within tandem clusters,which suggested that subfunctionalization had occurred among duplicate genes.The expression patterns of homologous gene pairs also changed,suggestive of the diversification of gene function during the evolution of diploid cotton.These findings provide insights into the mechanisms underlying the functional differentiation of duplicated NAC-TFs genes in two diploid cotton species.
