PMID- 21633322
OWN - NLM
STAT- MEDLINE
DCOM- 20111101
LR  - 20221207
IS  - 1744-6880 (Electronic)
IS  - 1744-6872 (Linking)
VI  - 21
IP  - 8
DP  - 2011 Aug
TI  - Genetic risk factors for type 2 diabetes mellitus and response to sulfonylurea 
      treatment.
PG  - 461-8
LID - 10.1097/FPC.0b013e3283478173 [doi]
AB  - OBJECTIVE: After the identification of type 2 diabetes mellitus (T2DM) risk 
      alleles from genome-wide association studies, models have been developed to 
      identify subjects at high risk to develop T2DM. We hypothesize that a panel of 20 
      repeatedly associated T2DM risk alleles influences response to sulfonylureas 
      (SUs). METHODS: Two hundred and seven incident SU (tolbutamide, glibenclamide, 
      glimepiride, gliclazide) users with T2DM were recruited from four primary care 
      centers. A genetic risk score per patient was calculated based on the number of 
      risk-alleles. With this score, patients were categorized into three predefined 
      genetic risk groups. The effect of the genetic risk group on the achievement of 
      stable SU dose, prescribed stable SU dose, and time to stable SU dose was 
      analyzed. RESULTS: Carriers of more than 17 T2DM risk alleles had a 1.7-fold 
      reduced likelihood to achieve stable SU dose (P=0.044). No significant effect of 
      the number of T2DM risk alleles on prescribed dose was found. Carriers of more 
      than 17 T2DM risk alleles showed a marginally significant increased time to 
      stable dose (hazard ratio: 0.81; 95% confidence interval, 0.75-1.01, P=0.058). 
      CONCLUSION: T2DM risk alleles are associated with response to SUs in primary care 
      T2DM patients. This suggests that individualization of T2DM treatment according 
      to genetic profile may be an opportunity to improve clinical outcome.
FAU - Swen, Jesse J
AU  - Swen JJ
AD  - Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 
      Leiden, The Netherlands.
FAU - Guchelaar, Henk-Jan
AU  - Guchelaar HJ
FAU - Baak-Pablo, Renee F
AU  - Baak-Pablo RF
FAU - Assendelft, Willem J J
AU  - Assendelft WJ
FAU - Wessels, Judith A M
AU  - Wessels JA
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Pharmacogenet Genomics
JT  - Pharmacogenetics and genomics
JID - 101231005
RN  - 0 (Biomarkers, Pharmacological)
RN  - 0 (Sulfonylurea Compounds)
SB  - IM
EIN - Pharmacogenet Genomics. 2012 Apr;22(4):325
MH  - Aged
MH  - *Biomarkers, Pharmacological
MH  - Diabetes Mellitus, Type 2/*drug therapy/*genetics
MH  - Female
MH  - Genetic Association Studies
MH  - Genetic Variation
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide
MH  - Risk Factors
MH  - Sulfonylurea Compounds/*therapeutic use
MH  - White People
EDAT- 2011/06/03 06:00
MHDA- 2011/11/02 06:00
CRDT- 2011/06/03 06:00
PHST- 2011/06/03 06:00 [entrez]
PHST- 2011/06/03 06:00 [pubmed]
PHST- 2011/11/02 06:00 [medline]
AID - 10.1097/FPC.0b013e3283478173 [doi]
PST - ppublish
SO  - Pharmacogenet Genomics. 2011 Aug;21(8):461-8. doi: 10.1097/FPC.0b013e3283478173.