Influence of cytochrome P450 oxidoreductase genetic polymorphisms on CYP1A2 activity and inducibility by smoking

Pharmacogenetics and Genomics
Maria DobrinasChin B Eap

Abstract

Cytochrome P4501A2 (CYP1A2) presents a high interindividual variability in its activity and also in its inducibility by smoking. Cytochrome P450 oxidoreductase (POR) is an electron transfer protein that catalyzes the activity of several cytochromes P450. We aimed to study the influence of POR genetic polymorphisms on CYP1A2 activity while smoking and after smoking cessation, as well as on CYP1A2 inducibility. CYP1A2 activity was determined by the paraxanthine/caffeine ratio in 184 smokers and in 113 of these smokers who were abstinent during a 4-week period. Participants were genotyped for POR rs17148944G>A, rs10239977C>T, rs3815455C>T, rs2286823G>A, rs2302429G>A, and rs1057868C>T (POR*28) polymorphisms. While smoking, none of the tested POR polymorphisms showed a significant influence on CYP1A2 activity. After smoking cessation, significantly higher CYP1A2 activity was found in POR rs2302429A carriers (P=0.038) and in carriers of rs17148944G-rs10239977C-rs3815455T-rs2286823G-rs2302429A-rs1057868T haplotype (P=0.038), whereas carriers of POR rs2286823A (P=0.031) and of the rs17148944G-rs10239977C-rs3815455C-rs2286823A-rs2302429G-rs1057868C haplotype (P=0.031) had decreased CYP1A2 activity. In the complete regression model, only...Continue Reading

References

Oct 1, 1995·Clinical Pharmacology and Therapeutics·O SpigsetR Dahlqvist
May 24, 2001·The Journal of Biological Chemistry·P A HubbardJ J Kim
Feb 5, 2003·The Journal of Biological Chemistry·Colin J HendersonC Roland Wolf
Mar 18, 2003·Journal of Clinical Psychopharmacology·Juan Antonio CarrilloJulio Benítez
Jun 23, 2004·Journal of Clinical Psychopharmacology·Chin B EapFranck Broly
Oct 26, 2005·Biochemical and Biophysical Research Communications·Bettie Sue Siler Masters
Mar 21, 2007·European Journal of Clinical Pharmacology·Roza GhotbiLeif Bertilsson
Sep 8, 2007·American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists·Lisa A Kroon
Jan 31, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ningwu HuangWalter L Miller
Jun 14, 2008·Pharmacogenetics and Genomics·Vishal AgrawalWalter L Miller
Oct 14, 2010·Pharmacogenetics and Genomics·Duanpen SandeeWalter L Miller
Nov 13, 2010·Molecular and Cellular Endocrinology·Walter L MillerKathleen M Giacomini
Dec 18, 2010·Endocrine Development·Christa E Flück, Amit V Pandey
May 20, 2011·Clinical Pharmacology and Therapeutics·Maria DobrinasChin B Eap

Citations

Aug 6, 2014·Current Hypertension Reports·Idris GuessousMurielle Bochud
Jan 29, 2013·Pharmacology & Therapeutics·Amit V Pandey, Christa E Flück
Jun 3, 2014·Pharmacology & Therapeutics·Payman ShahabiSophie Visvikis-Siest
May 7, 2013·Expert Opinion on Drug Metabolism & Toxicology·Vidya PereraAndrew J McLachlan
Jul 17, 2012·Gynecologic Oncology·Lucy S HodgeTimothy S Tracy
Oct 11, 2012·Pharmacogenetics and Genomics·Lei HuLan Fan
Aug 5, 2014·Therapeutic Drug Monitoring·Fabian CzerwenskyWerner Steimer
Mar 16, 2013·Pharmacogenetics and Genomics·Maria DobrinasChin B Eap

Related Concepts

CYP1A2 protein, human
Quick-Pep
Enzyme Induction
Genetic Polymorphism
Cigar smoker
Cessation of Smoking
Cytochrome P-450 CYP1A2
Cytochrome P450
Regression Analysis
1,7-dimethylxanthine

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Lipidomics & Rhinovirus Infection

Lipidomics can be used to examine the lipid species involved with pathogenic conditions, such as viral associated inflammation. Discovered the latest research on Lipidomics & Rhinovirus Infection.

Alzheimer's Disease: MS4A

Variants within the membrane-spanning 4-domains subfamily A (MS4A) gene cluster have recently been implicated in Alzheimer's disease in genome-wide association studies. Here is the latest research on Alzheimer's disease and MS4A.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Torsion Dystonia

Torsion dystonia is a movement disorder characterized by loss of control of voluntary movements appearing as sustained muscle contractions and/or abnormal postures. Here is the latest research.

Generating Insulin-Secreting Cells

Reprogramming cells or using induced pluripotent stem cells to generate insulin-secreting cells has significant therapeutic implications for diabetics. Here is the latest research on generation of insulin-secreting cells.

Central Pontine Myelinolysis

Central Pontine Myelinolysis is a neurologic disorder caused most frequently by rapid correction of hyponatremia and is characterized by demyelination that affects the central portion of the base of the pons. Here is the latest research on this disease.

Epigenome Editing

Epigenome editing is the directed modification of epigenetic marks on chromatin at specified loci. This tool has many applications in research as well as in the clinic. Find the latest research on epigenome editing here.