Influence of the Genetic Polymorphisme in the 5′ Flanking and Exonic Regions of CYP2C19 on Proguanil Oxidation

• SATYANARAYANA Chakradhara Rao Uppugunduri

  Pharmacogenomics Laboratory, Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)

• DEVENDRAN Anichavezhi

  Pharmacogenomics Laboratory, Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)

• JAYARAMAN Muthukumaran

  Centre for Bioinformatics, Pondicherry University

• MANNU Jayakanthan

  Centre for Bioinformatics, Pondicherry University

• MATHUR Premendu P.

  Centre for Bioinformatics, Pondicherry University

• GOPAL Shewade Deepak

  Pharmacogenomics Laboratory, Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)

• RAJAGOPAL Krishnamoorthy

  U 763, INSERM, Hopital Robert Debre

• CHANDRASEKARAN Adithan

  Pharmacogenomics Laboratory, Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)

書誌事項

タイトル別名

• Influence of the Genetic Polymorphisms in the 5' Flanking and Exonic Regions of CYP2C19 on Proguanil Oxidation

抄録

  CYP2C19 is a polymorphic enzyme which metabolizes several clinically important drugs including proguanil. Variation in the 5′ regulatory region may influence CYP2C19 activity. This study evaluates the relationship between proguanil metabolic ratio and genetic variations of CYP2C19 in a South Indian population. Fifty unrelated healthy subjects were genotyped for CYP2C19 ^*2 and ^*3 alleles and the 5′ flanking region of CYP2C19 was sequenced. Plasma concentrations of proguanil and cycloguanil were estimated by reverse phase HPLC after single oral doses (200 mg) of proguanil. In silico docking analysis of transcription factors binding to its sites in CYP2C19 5′ regulatory region was performed. The mean metabolic ratios (proguanil/cycloguanil) were highest in ^*1/^*2 or ^*1/^*3 subjects and in ^*2/^*2 or ^*2/^*3 as compared to ^*1/^*1 subjects. Subjects with promoter region variation -98T>C showed decrease in the metabolic ratios irrespective of other variation, which may explain the deviation from the genotype-phenotype association of CYP2C19. In silico analysis predicted alteration in the interaction of transcription factors to their binding sites in the presence of variant alleles. The results of this study would be useful in predicting interindividual differences in the metabolism of substrates of CYP2C19.<br>

収録刊行物

• Ｄｒｕｇ　Ｍｅｔａｂｏｌｉｓｍ　ａｎｄ　Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ

  Ｄｒｕｇ　Ｍｅｔａｂｏｌｉｓｍ　ａｎｄ　Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ 24 (6), 537-548, 2009

  日本薬物動態学会

キーワード

• <i>CYP2C19</i>
• promoter
• transcription
• variant alleles
• transcription factor
• phenotype
• docking
• South Indian

詳細情報

• CRID: 1390001205180700928
• NII論文ID: 10027119696
• NII書誌ID: AA1162652X
• DOI: 10.2133/dmpk.24.537
• ISSN: 18800920
• ISSN: 13474367
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715301464?httpAccept=text/xml
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715301464?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2010179450
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可