• Title/Summary/Keyword: CYP2D6 genotype

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Impact of CYP2D6 Polymorphisms on Tamoxifen Responses of Women with Breast Cancer: A Microarray-based Study in Thailand

  • Sukasem, Chonlaphat;Sirachainan, Ekaphop;Chamnanphon, Montri;Pechatanan, Khunthong;Sirisinha, Thitiya;Ativitavas, Touch;Panvichian, Ravat;Ratanatharathorn, Vorachai;Trachu, Narumol;Chantratita, Wasun
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.9
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    • pp.4549-4553
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    • 2012
  • This study was designed to investigate the frequency of CYP2D6 polymorphisms and evaluate the association between genetic polymorphisms of CYP2D6 and tamoxifen therapeutic outcome in Thai breast cancer patients. We recruited 48 breast cancer patients who received adjuvant tamoxifen for evaluating CYP2D6 genetic polymorphisms using microarray-based technology. Associations between genotypes-phenotypes and disease free survival were analyzed. Median follow up time was 5.6 years. The mean age of the subjects was 50 years. The 3 common allelic frequencies were 43.8% ($^*10$), 36.5 ($^*1$) and 10.4% ($^*2$) which are related to extensive metabolizer (EM) and intermediate metabolizer (IM) with 70.8% and 29.2 %, respectively. No association between CYP2D6 genotypes and DFS was demonstrated. Nevertheless, exploratory analysis showed statistically significant shorter DFS in the IM group of post-menopause patients (HR, 6.85; 95%CI, 1.48-31.69; P=0.005). Furthermore, we observed statistically significant shorter DFS of homozygous $CYP2D6^*10$ when compared with heterozygous CYP2D6*10 and other genotypes (P=0.005). $CYP2D6^*10$ was the most common genotype in our subjects. Post-menopause patients with homozygous $CYP2D6^*10$ and IM have shorter DFS. To confirm this relationship, larger samples and comprehensively designed trials in Thailand are required.

The Effect of CYP2D6/3A5 Genotypes on Plasma Concentrations of Haloperidol after Adjunctive Treatment of Aripiprazole

  • Shim, Joo-Cheol;Ahn, Jung-Mi;Jung, Do-Un;Kong, Bo-Geum;Kang, Jae-Wook;Liu, Kwang-Hyeon;Shin, Jae-Gook
    • Korean Journal of Biological Psychiatry
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    • v.18 no.2
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    • pp.95-100
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    • 2011
  • Objectives To evaluate the drug interactions between aripiprazole and haloperidol, authors investigated plasma concentrations of those drugs by genotypes. Method Fifty six patients with a confirmed Diagnostic and Statistical Manual of Mental Disorders 4th edition diagnosis of schizophrenia were enrolled in this eight-week, double blind, placebo-controlled study. Twenty-eight patients received adjunctive aripiprazole treatment and twenty-eight patients received placebo while being maintained on haloperidol treatment. Aripiprazole was dosed at 15 mg/day for the first 4 weeks, and then 30 mg for the next 4 weeks. The haloperidol dose remained fixed throughout the study. Plasma concentrations of haloperidol and aripiprazole were measured by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) at baseline, week 1, 2, 4 and 8. $^*1$, $^*5$, and $^*10$ B alleles of CYP2D6 and $^*1$ and $^*3$ alleles of CYP3A5 were determined. The Student's T-test, Pearson's Chi-square test, Wilcoxon Rank Sum test and Logistic Regression analysis were used for data analysis. All tests were two-tailed and significance was defined as an alpha < 0.05. Results In the frequency of CYP2D6 genotype, $^*1/^*10$ B type was most frequent (36.5%) and $^*1/^*1$ (30.8%), $^*10B/^*10B$ (17.3%) types followed. In the frequency of CYP3A5 genotype, $^*3/^*3$ type was found in 63.5% of subjects, and $^*1/^*3$ type and $^*1/^*1$ were 30.8% and 5.8% respectively. The plasma levels of haloperidol and its metabolites did not demonstrate significant time effects and time-group interactions after adjunctive treatment of aripiprazole. The genotypes of CYP2D6 and 3A5 did not affect the plasma concentration of haloperidol in this trial. No serious adverse event was found after adding aripiprazole to haloperidol. Conclusion No significant drug interaction was found between haloperidol and aripiprazole. Genotypes of CYP2D6 and 3A5 did not affect the concentration of haloperidol after adding aripiprazole.

Polymorphysims of CYP17-I Gene in the Exons Were Associated with the Reproductive Endocrine of Japanese Flounder (Paralichthys olivaceus)

  • Ma, R.Q.;He, F.;Wen, H.S.;Li, J.F.;Mu, W.J.;Liu, M.;Zhang, Y.Q.;Hu, J.;Qun, L.
    • Asian-Australasian Journal of Animal Sciences
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    • v.25 no.6
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    • pp.794-799
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    • 2012
  • The cytochrome P450c17-I (CYP17-I) is one of the enzymes critical to gonadal development and the synthesis of androgens. Two single nucleotide polymorphisms (SNPs) were detected within the coding region of the CYP17-I gene in a population of 75 male Japanese flounder (Paralichthys olivaceus). They were SNP1 (c.C445T) located in exon2 and SNP2 (c.T980C (p.Phe307Leu)) located in exon5. Four physiological indices, which were serum testosterone (T), serum $17{\beta}$-estradiol ($E_2$), Hepatosomatic index (HSI), and Gonadosomatic index (GSI), were studied to examine the effect of the two SNPs on the reproductive endocrines of Japanese flounder. Multiple comparisons revealed that CT genotype of SNP1 had a much lower T level than CC genotype (p<0.05) and the GSI of individuals with CC genotype of SNP2 was higher than those with TT genotype (p<0.05). Four diplotypes were constructed based on the two SNPs and the diplotype D3 had a significantly lower T level and GSI. In conclusion, the two SNPs were significantly associated with reproductive traits of Japanese flounder.

EFFECTS OF CYP2D6*10 GENOTYPE AND CYP3A4 INHIBITION ON THE DISPOSITION AND NEUROLOGICAL SIDE EFFECTS OF HALOPERIDOL IN HUMAN SUBJECTS

  • Park, Ji-Young;Shon, Ji-Hong;Yoon, Young-Ran;Kim, Kyung-Ah;Kim, Min-Jung;Shim, Ju-Chul;Cha, In-June;Shin, Jae-Gook
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.05a
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    • pp.149-149
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    • 2001
  • Cytochrome P450 (CYP) 2D6 and CYP3A4 have been reported to be involved in the major metabolic pathways and formations of neurotoxic metabolites (HPP$\^$+/, RHPP$\^$+/) from haloperidol (HAL). However, no in vivo study has been addressed to the involvement of both CYP isoforms on the formation of toxic HAL metabolites.(omitted)

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Four Times of Relapse of Plasmodium vivax Malaria Despite Primaquine Treatment in a Patient with Impaired Cytochrome P450 2D6 Function

  • Choi, Sungim;Choi, Heun;Park, Seong Yeon;Kwak, Yee Gyung;Song, Je Eun;Shin, So Youn;Baek, Ji Hyeon;Shin, Hyun-IL;Oh, Hong Sang;Kim, Yong Chan;Yeom, Joon-Sup;Han, Jin-Hee;Kim, Min Jae
    • Parasites, Hosts and Diseases
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    • v.60 no.1
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    • pp.39-43
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    • 2022
  • Plasmodium vivax exhibits dormant liver-stage parasites, called hypnozoites, which can cause relapse of malaria. The only drug currently used for eliminating hypnozoites is primaquine. The antimalarial properties of primaquine are dependent on the production of oxidized metabolites by the cytochrome P450 isoenzyme 2D6 (CYP2D6). Reduced primaquine metabolism may be related to P. vivax relapses. We describe a case of 4 episodes of recurrence of vivax malaria in a patient with decreased CYP2D6 function. The patient was 52-year-old male with body weight of 52 kg. He received total gastrectomy and splenectomy 7 months before the first episode and was under chemotherapy for the gastric cancer. The first episode occurred in March 2019 and each episode had intervals of 34, 41, and 97 days, respectively. At the first and second episodes, primaquine was administered as 15 mg for 14 days. The primaquine dose was increased with 30 mg for 14 days at the third and fourth episodes. Seven gene sequences of P. vivax were analyzed and revealed totally identical for all the 4 samples. The CYP2D6 genotype was analyzed and intermediate metabolizer phenotype with decreased function was identified.