title: Roles of CYP2C19 Gene Polymorphisms in Susceptibility to POAG and Individual Differences in Drug Treatment Response.
abstract: BACKGROUND
  The aim of this study was to investigate the roles of cytochrome P450 2C19 (CYP2C19) polymorphisms in primary open-angle glaucoma (POAG) susceptibility and individual responses to drug treatment.
  
  
  METHODS
  This case-control study consisted of 93 cases with POAG and 125 controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze CYP2C19 single-nucleotide polymorphisms (SNPs). After timolol treatment, patients were classified into side effect (SE) group and non-side effect (NSE) group. According to drug treatment responses, patients were divided into 3 groups: excellent group (Ex) (IOP ≥8 mm Hg); utility group (Ut) (5 <IOP ≤8 mm Hg), and ineffective group (In) (IOP ≤5 mm Hg). Data analysis was performed using SPSS software.
  
  
  RESULTS
  We found no statistical differences in the alleles and genotypes frequencies of CYP2C19 between the case group and the control group (both P>0.05). Frequencies of extensive metabolizer phenotype and poor metabolizer phenotype or poor metabolizer phenotype and intermediate metabolizer phenotype were significantly different between the SE group and NSE group (both P<0.05). The distribution of intermediate metabolizer phenotype and extensive metabolizer phenotype were significantly different among Ex group, Ut group, and In group (all P<0.05).
  
  
  CONCLUSIONS
  We found no evidence that CYP2C19 polymorphisms are associated with susceptibility to POAG. However, different CYP2C19 metabolizer phenotypes were identified and observed to have important effects on the individual differences in drug treatment response.
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Beihua University, Jilin City, Jilin, China (mainland).
authors.forename: Xiang-Long
authors.initials: XL
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, Central Hospital of Jilin, Jilin City, Jilin, China (mainland).
authors.forename: Qiu-Ju
authors.initials: QJ
authors.lastname: Jia
authors.affiliation: Department of Ophthalmology, China-Japan Union Hospital of Jilin University, Jilin City, Jilin, China (mainland).
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Jilin Cancer Hospital, Changchun, Jilin, China (mainland).
authors.forename: Zong-Ming
authors.initials: ZM
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, The First People's Hospital of Yueyang, Yueyang, Hunan, China (mainland).
authors.forename: Hai
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, The First People's Hospital of Yueyang, Yueyang, Hunan, China (mainland).
authors.forename: Xuan-Chu
authors.initials: XC
authors.lastname: Duan
authors.affiliation: Department of Ophthalmology, China-Japan Union Hospital of Jilin University, Jilin City, Jilin, China (mainland).
authors.forename: Xue-Man
authors.initials: XM
authors.lastname: Lyu
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005902:Glaucoma, Open-Angle / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013999:Timolol / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D013999:Timolol; D065731:Cytochrome P-450 CYP2C19
references.citation: J Ocul Pharmacol Ther. 2009 Apr;25(2):163-71
references.pmid: 19284319
references.citation: Biochem J. 2010 Aug 1;429(3):435-49
references.pmid: 20626352
references.citation: J Ocul Pharmacol Ther. 2013 Sep;29(7):639-45
references.pmid: 23530946
references.citation: Ophthalmology. 2014 Aug;121(8):1558-65
references.pmid: 24746386
references.citation: JACC Cardiovasc Interv. 2012 Dec;5(12):1280-7
references.pmid: 23257377
references.citation: PLoS One. 2013;8(3):e58657
references.pmid: 23536807
references.citation: Invest Ophthalmol Vis Sci. 2011;52(11):7817-21
references.pmid: 21873661
references.citation: J Glaucoma. 2016 Feb;25(2):149-54
references.pmid: 25333612
references.citation: Invest Ophthalmol Vis Sci. 2010 Mar;51(3):1289-96
references.pmid: 19850848
references.citation: Pharmacol Ther. 2013 Apr;138(1):103-41
references.pmid: 23333322
references.citation: Am J Ophthalmol. 2011 Apr;151(4):671-81
references.pmid: 21257146
references.citation: BMC Ophthalmol. 2011;11:23
references.pmid: 21851642
references.citation: Clin Ophthalmol. 2014 Aug 25;8:1579-90
references.pmid: 25210425
references.citation: Eur Heart J. 2010 Dec;31(24):3046-53
references.pmid: 20833683
references.citation: Clin Pharmacol Ther. 2011 Aug;90(2):328-32
references.pmid: 21716271
references.citation: Basic Clin Pharmacol Toxicol. 2010 Apr;106(4):302-9
references.pmid: 19912165
references.citation: Iran J Pharm Res. 2014 Spring;13(2):599-612
references.pmid: 25237356
references.citation: PLoS Genet. 2012;8(5):e1002611
references.pmid: 22570627
references.citation: Basic Clin Pharmacol Toxicol. 2011 May;108(5):297-303
references.pmid: 21385322
references.citation: Invest Ophthalmol Vis Sci. 2012 May;53(6):3221-5
references.pmid: 22511635
references.citation: Pharmacogenomics J. 2013 Feb;13(1):1-11
references.pmid: 23089672
references.citation: JAMA. 2011 Dec 28;306(24):2704-14
references.pmid: 22203539
references.citation: Clin Pharmacol Ther. 2011 Oct;90(4):561-7
references.pmid: 21918510
references.citation: Acta Ophthalmol. 2014 Mar;92(2):e133-40
references.pmid: 24020826
references.citation: Circ Cardiovasc Interv. 2011 Dec 1;4(6):585-94
references.pmid: 22045970
references.citation: Clin Pharmacokinet. 2009;48(11):689-723
references.pmid: 19817501
references.citation: JAMA. 2011 Nov 23;306(20):2221-8
references.pmid: 22088980
references.citation: Br J Clin Pharmacol. 2012 Jan;73(1):93-105
references.pmid: 21689142
references.citation: Med Sci Monit. 2014;20:2213-8
references.pmid: 25381554