RESUMO
The gene encoding the putative reductase component (KshB) of 3-ketosteroid 9α-hydroxylase was cloned from Rhodococcus equi USA-18, a cholesterol oxidase-producing strain formerly named Arthrobacter simplex USA-18, by PCR according to consensus amino acid motifs of several bacterial KshB subunits. Deletion of the gene in R. equi USA-18 by a PCR-targeted gene disruption method resulted in a mutant strain that could accumulate up to 0.58 mg/ml 1,4-androstadiene-3,17-dione (ADD) in the culture medium when 0.2% cholesterol was used as the carbon source, indicating the involvement of the deleted enzyme in 9α-hydroxylation of steroids. In addition, this mutant also accumulated 3-oxo-23,24-bisnorchola-1,4-dien-22-oic acid (Δ1,4-BNC). Because both ADD and Δ1,4-BNC are important intermediates for the synthesis of steroid drugs, this mutant derived from R. equi USA-18 may deserve further investigation for its application potential.
Assuntos
Androstadienos/metabolismo , Deleção de Genes , Oxigenases de Função Mista/genética , Oxirredutases/genética , Rhodococcus equi/genética , Esteroides/química , Esteróis/metabolismo , Androstadienos/química , Biotransformação , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Cromossomos Bacterianos/genética , Técnicas de Inativação de Genes , Genes Bacterianos , Humanos , Macrófagos/microbiologia , Espectrometria de Massas , Reação em Cadeia da Polimerase , Padrões de Referência , Reprodutibilidade dos Testes , Rhodococcus equi/enzimologia , Rhodococcus equi/crescimento & desenvolvimento , Esteroides/metabolismo , Esteróis/química , Fatores de TempoRESUMO
UNLABELLED: The aim of the present study was to evaluate the association between the polymorphisms of the EXO1 gene and the risk of breast cancer in central Taiwan. PATIENTS AND METHODS: In this hospital-based study, the association of EXO1 A1419G (rs3754093), C908G (rs10802996), A238G (rs1776177), C498T (rs1635517), K589E (rs1047840), G670E (rs1776148), C723R (rs1635498), L757P (rs9350) and C3114T (rs851797) polymorphisms with breast cancer risk in a central Taiwanese population was investigated. In total, 1,272 patients with breast cancer and 1,272 age- and gender-matched healthy controls recruited from the China Medical University Hospital were genotyped. RESULTS: A significantly different distribution was found in the frequency of the EXO1 K589E genotype, but not the other genotypes, between the breast cancer and control groups. The A allele EXO1 K589E conferred a significantly (p=0.000025) increased risk of breast cancer. As for the rest of the polymorphisms, there was no difference in distribution between the breast cancer and control groups. CONCLUSION: Our results provide evidence that the A allele of EXO1 K589E may be associated with the development of breast cancer and may be a useful biomarker for breast cancer detection and primary prevention.
Assuntos
Neoplasias da Mama/genética , Enzimas Reparadoras do DNA/genética , Exodesoxirribonucleases/genética , Alelos , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Humanos , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , TaiwanRESUMO
AIM: To evaluate the association between the polymorphisms of the Ku80 gene and the risk of colorectal cancer in Central Taiwan. MATERIALS AND METHODS: In this hospital-based case-control study, the association of Ku80 G-1401T rs828907, Ku80 C-319T rs11685387 and Ku80 intron 19 rs9288518 polymorphisms with colorectal cancer risk in a central Taiwanese population was investigated. In total, 362 patients with colorectal cancer and 362 age- and gender-matched healthy controls recruited from the China Medical Hospital in central Taiwan were genotyped. RESULTS: A significantly different distribution was found in the frequency of the Ku80 G-1401T genotype, but not the Ku80 C-319T or intron 19 genotypes, between the colorectal cancer and control groups. The T allele Ku80 G-1401T conferred a significantly (p=0.0069) increased risk of colorectal cancer. As for Ku80 C-319T and intron 19 polymorphisms, there was no difference in distribution between the colorectal cancer and control groups. Gene interactions with smoking, but not with alcohol consumption, were significant for Ku80 G-1401T polymorphism. The Ku80 G-1401T GT and TT genotype in association with smoking conferred an increased risk of 2.537 (95% confidence interval=1.398-4.601) for colorectal cancer. CONCLUSION: These results provide the first evidence that the T allele of the Ku80 G-1401T may be associated with the development of colorectal cancer and may be a novel useful marker for primary prevention and anticancer intervention.
