Maruf A A, Ahmed M U, Azad M A K, Ahmed M, Hasnat A
Department of Clinical Pharmacy & Pharmacology, Faculty of Pharmacy, University of Dhaka.
Bangladesh Med Res Counc Bull. 2012 Apr;38(1):1-5. doi: 10.3329/bmrcb.v38i1.6978.
The purpose of this study is to investigate the genotype and allelic frequencies of CYP3A in Bangladeshi Tuberculosis (TB) patients which may help for individualized drug dosing and improved therapeutics. Genotyping was done using the extracted genomic DNA from 90 TB patients followed by amplification of target alleles by Polymerase Chain Reaction (PCR). Amplified alleles were then digested by restriction enzymes followed by gel electrophoresis & sequencing to identify the targeted alleles namely CYP3A41B, CYP3A42, CYP3A44, CY3A45, CYP3A46, CYP3A410, CYP3A418, and CYP3A53. In TB patients, no samples were positive for CYP3A42, CYP3A44, CYP3A45, CYP3A46, CYP3A410, and CYP3A418 alleles. One sample was found to be heterozygous for CYP3A41B (1.11%). The wild homozygous (CYP3A51/1) genotype frequency was 7.78%, the heterozygous (CYP3A51/3) frequency was 42.22% and the homozygous mutant (CYP3A53/*3) frequency was 50% in Bangladeshi TB patients. The absence of the common polymorphic gene suggests that there will be no impact of CYP3A drug metabolizing enzymes on antituberculosis drugs.
本研究的目的是调查孟加拉国结核病(TB)患者中CYP3A的基因型和等位基因频率,这可能有助于实现个体化给药并改善治疗效果。使用从90名TB患者中提取的基因组DNA进行基因分型,随后通过聚合酶链反应(PCR)扩增目标等位基因。然后用限制性内切酶消化扩增的等位基因,接着进行凝胶电泳和测序,以鉴定目标等位基因,即CYP3A41B、CYP3A42、CYP3A44、CY3A45、CYP3A46、CYP3A410、CYP3A418和CYP3A53。在TB患者中,没有样本的CYP3A42、CYP3A44、CYP3A45、CYP3A46、CYP3A410和CYP3A418等位基因呈阳性。发现一个样本的CYP3A41B为杂合子(1.11%)。在孟加拉国TB患者中,野生纯合子(CYP3A51/1)基因型频率为7.78%,杂合子(CYP3A51/3)频率为42.22%,纯合突变体(CYP3A53/*3)频率为50%。常见多态性基因的缺失表明CYP3A药物代谢酶对抗结核药物没有影响。