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Variation in CDKAL1 gene is associated with therapeutic response to sulphonylureas.
MedLine Citation:
PMID:  22292718     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The aim of the present pilot pharmacogenetic study was to analyse quantitative effects of sulphonylurea treatment in addition to metformin on parameters of glycaemic control with respect to CDKAL1 genotypes in patients with type 2 diabetes. Effect of 6-month sulphonylurea therapy on glycaemic control according to CDKAL1 genotypes was evaluated in 101 patients with type 2 diabetes who failed to achieve glycaemic control on metformin monotherapy. CDKAL1 rs7756992 polymorphism was determined by melting curve analysis of small amplicon following real-time PCR. After sulphonylurea treatment fasting plasma glucose (FPG) levels were significantly different (p=0.045) among three CDKAL1 genotype groups (AA: n=49; AG: n=36; GG: n=16). In a dominant genetic model, carriers of the G-allele (AG+GG, n=52) achieved significantly lower FPG levels in comparison with patients with the AA genotype (6.90+/-1.08 vs. 7.48+/-1.12 mmol/l, p=0.013). Consequently, adjusted deltaFPG was significantly higher in the AG+GG compared to the AA group (1.48+/-1.51 vs. 1.02+/-1.33 mmol/l, p=0.022). Similar trend was observed for HbA(1c) levels, but the difference between the genotype groups did not reach the level of statistical significance. Relatively small number of included patients is a limitation of the present study. In conclusion, our results suggest that the magnitude of FPG reduction after 6-month sulphonylurea treatment in patients with type 2 diabetes is related to the variation in CDKAL1.
Authors:
Z Schroner; M Javorský; J Halušková; L Klimčáková; E Babjaková; M Fabianová; E Slabá; M Kozárová; I Tkáč
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-31
Journal Detail:
Title:  Physiological research / Academia Scientiarum Bohemoslovaca     Volume:  -     ISSN:  1802-9973     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-2-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9112413     Medline TA:  Physiol Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Internal Medicine 4, L. Pasteur University Hospital, Košice, Slovakia. ivantkac@lf.upjs.sk.
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