PMID- 19891554
OWN - NLM
STAT- MEDLINE
DCOM- 20100112
LR  - 20141120
IS  - 1744-8042 (Electronic)
IS  - 1462-2416 (Linking)
VI  - 10
IP  - 11
DP  - 2009 Nov
TI  - Presence of CYP2C9*3 allele increases risk for hypoglycemia in Type 2 diabetic 
      patients treated with sulfonylureas.
PG  - 1781-7
LID - 10.2217/pgs.09.96 [doi]
AB  - AIMS: Hypoglycemia is a common adverse effect of sulfonylurea oral hypoglycemic 
      agents. Impaired metabolism of sulfonylureas due to gene polymorphisms in the 
      metabolic enzyme CYP2C9 might lead to hypoglycemia. In the present study we 
      explored the association of the CYP2C9 variant alleles CYP2C9*2 and CYP2C9*3 with 
      the incidence of hypoglycemic events in diabetic patients receiving the 
      sulfonylureas glimepiride and gliclazide. MATERIALS & METHODS: A total of 92 Type 
      2 diabetes mellitus (T2DM) patients receiving sulfonylurea and reporting 
      drug-associated hypoglycemia, and 84 T2DM patients receiving sulfonylurea and 
      having never experienced hypoglycemia were included in the study. A sample of 283 
      nondiabetic controls that had been genotyped earlier served as a second control 
      group. CYP2C9*2 and *3 alleles were detected by use of PCR-RFLP analysis. 
      RESULTS: Frequencies of CYP2C9*1/*3 genotype and CYP2C9*3 allele were 
      significantly lower in T2DM patients than nondiabetic controls (p = 0.003 and p = 
      0.017, respectively). A total of 11 out of 92 subjects (12%) experiencing 
      hypoglycemia carried the CYP2C9*3 allele, as opposed to only 1 out of 84 subjects 
      (1.2%) free of sulfonylurea-induced hypoglycemia. In a model adjusted for age, 
      BMI, mean daily dose of sulfonylurea, duration of T2DM and renal function, 
      CYP2C9*1/*3 genotype increased the hypoglycemia risk in response to sulfonylurea 
      (odds ratio: 1.687; p = 0.011). However, no differences in CYP2C9*2 allele 
      frequency between the two groups were found. DISCUSSION & CONCLUSION: The 
      presence of CYP2C9*3 appears to be protective for development of T2DM. 
      Furthermore, in T2DM patients, CYP2C9*3 increases the risk of hypoglycemia when 
      they are treated with sulfonylureas, possibly due to impaired metabolism of these 
      drugs. CYP2C9 genotyping might thus be a useful tool for predicting adverse 
      effects caused by sulfonylureas and help clinicians in safer prescribing of oral 
      hypoglycemic agents. The potential T2DM protective effect of CYP2C9*3 allele 
      requires further investigation.
FAU - Ragia, Georgia
AU  - Ragia G
AD  - Laboratory of Pharmacology, Medical School, Democritus University of Thrace, 
      Dragana Campus, 68100 Alexandroupolis, Greece.
FAU - Petridis, Ioannis
AU  - Petridis I
FAU - Tavridou, Anna
AU  - Tavridou A
FAU - Christakidis, Dimitrios
AU  - Christakidis D
FAU - Manolopoulos, Vangelis G
AU  - Manolopoulos VG
LA  - eng
PT  - Journal Article
PL  - England
TA  - Pharmacogenomics
JT  - Pharmacogenomics
JID - 100897350
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Sulfonylurea Compounds)
RN  - EC 1.14.13.- (CYP2C9 protein, human)
RN  - EC 1.14.13.- (Cytochrome P-450 CYP2C9)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Alleles
MH  - Aryl Hydrocarbon Hydroxylases/*genetics
MH  - Case-Control Studies
MH  - Cytochrome P-450 CYP2C9
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Hypoglycemia/etiology/*genetics
MH  - Hypoglycemic Agents/adverse effects
MH  - Male
MH  - Middle Aged
MH  - Risk
MH  - Sulfonylurea Compounds/*adverse effects
EDAT- 2009/11/07 06:00
MHDA- 2010/01/13 06:00
CRDT- 2009/11/07 06:00
PHST- 2009/11/07 06:00 [entrez]
PHST- 2009/11/07 06:00 [pubmed]
PHST- 2010/01/13 06:00 [medline]
AID - 10.2217/pgs.09.96 [doi]
PST - ppublish
SO  - Pharmacogenomics. 2009 Nov;10(11):1781-7. doi: 10.2217/pgs.09.96.