Document Detail

Genetic risk factors for type 2 diabetes mellitus and response to sulfonylurea treatment.
MedLine Citation:
PMID:  21633322     Owner:  NLM     Status:  MEDLINE    
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.
Jesse J Swen; Henk-Jan Guchelaar; Renée F Baak-Pablo; Willem J J Assendelft; Judith A M Wessels
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Pharmacogenetics and genomics     Volume:  21     ISSN:  1744-6880     ISO Abbreviation:  Pharmacogenet. Genomics     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-07-12     Completed Date:  2011-11-01     Revised Date:  2012-04-24    
Medline Journal Info:
Nlm Unique ID:  101231005     Medline TA:  Pharmacogenet Genomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  461-8     Citation Subset:  IM    
Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
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MeSH Terms
Biomarkers, Pharmacological*
Diabetes Mellitus, Type 2 / drug therapy*,  genetics*
European Continental Ancestry Group
Genetic Association Studies
Genetic Variation
Middle Aged
Polymorphism, Single Nucleotide
Risk Factors
Sulfonylurea Compounds / therapeutic use*
Reg. No./Substance:
0/Biomarkers, Pharmacological; 0/Sulfonylurea Compounds
Erratum In:
Pharmacogenet Genomics. 2012 Apr;22(4):325

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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