Format

Send to

Choose Destination
See comment in PubMed Commons below
Joint Bone Spine. 2014 Mar;81(2):160-3. doi: 10.1016/j.jbspin.2013.07.006. Epub 2013 Aug 7.

Frequency of CYP2C9 polymorphisms in Polynesian people and potential relevance to management of gout with benzbromarone.

Author information

  • 1Department of Surgical Sciences, University of Otago, Dunedin School of Medicine, PO Box 913, 9054 Dunedin, New Zealand. Electronic address: rebecca.roberts@otago.ac.nz.
  • 2Department of Surgical Sciences, University of Otago, Dunedin School of Medicine, PO Box 913, 9054 Dunedin, New Zealand.
  • 3Department of Pharmacy, University of Otago, Dunedin, New Zealand.
  • 4Department of Biochemistry, University of Otago, Dunedin, New Zealand.
  • 5Department of Medicine, University of Auckland, Auckland, New Zealand.
  • 6Department of Medicine, University of Otago, Christchurch, New Zealand.
  • 7Department of Medicine, University of Otago, Wellington, New Zealand.

Abstract

OBJECTIVES:

Gout is a major health problem in Polynesians and allopurinol, the drug of choice for the management gout, appears to be less effective in Polynesian patients. The uricosuric drug benzbromarone is an alternative treatment but CYP2C9 poor metabolisers (PMs) may be at a heightened risk of benzbromarone-induced hepatotoxicity. The objectives of this study were to determine the frequency of the PM alleles CYP2C9*2 and CYP2C9*3 in New Zealand (NZ) Caucasian and Polynesian gout cohorts; and then to test for novel CYP2C9 polymorphisms in Polynesians.

METHODS:

Eight hundred and fifty-two Caucasians (537 controls, 315 gout patients) and 1072 Māori and Pacific Island (Polynesian) people (620 controls, 452 gout patients) were genotyped for CYP2C9*2 and CYP2C9*3. Forty Polynesians were screened for novel CYP2C9 polymorphisms using whole genome sequencing.

RESULTS:

Frequency of CYP2C9 PM alleles was significantly higher in Caucasians compared to Polynesians (CYP2C9*2: 13.5% versus 3.1%; CYP2C9*3: 5.5% versus 1.6%, P<1.2E-11). Within Polynesians, CYP2C9 PM alleles were rarer in Western Polynesians (Samoa, Tonga) than Eastern Polynesians (NZ and Cook Island Maori; CYP2C9*2: 0.6% versus 2.5%; CYP2C9*3: 0.4% versus 2.0%; P<0.03). A total of 152 SNPs were found by sequencing. None of these variants were predicted by in silico analysis to significantly impact on CYP2C9 expression or activity.

CONCLUSION:

Prospective CYP2C9 genotyping of Caucasian gout patients may be warranted for benzbromarone, whereas the low frequencies of CYP2C9 PM alleles in Polynesians suggests that the CYP2C9 polymorphism may be of little or no relevance to benzbromarone prescribing in this population.

Copyright © 2013 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

KEYWORDS:

CYP2C9 poor metabolizer allele; Hepatotoxicity; Uricosuric agent

[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk