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Articles by E. van t Riet
Total Records ( 1 ) for E. van t Riet
  B. Guigas , J. E. de Leeuw van Weenen , N. van Leeuwen , A. M. Simonis-Bik , T. W. van Haeften , G. Nijpels , J. J. Houwing-Duistermaat , M. Beekman , J. Deelen , L. M. Havekes , B. W. J. H. Penninx , N. Vogelzangs , E. van t Riet , A. Dehghan , A. Hofman , J. C. Witteman , A. G. Uitterlinden , N. Grarup , T. Jorgensen , D. R. Witte , T. Lauritzen , T. Hansen , O. Pedersen , J. Hottenga , J. A. Romijn , M. Diamant , M. H. H. Kramer , R. J. Heine , G. Willemsen , J. M. Dekker , E. M. Eekhoff , H. Pijl , E. J. de Geus , P. E. Slagboom and L. M. t Hart
 

Aims

Modulation of dopamine receptor D2 (DRD2) activity affects insulin secretion in both rodents and isolated pancreatic β-cells. We hypothesized that single nucleotide polymorphisms in the DRD2/ANKK1 locus may affect susceptibility to Type 2 diabetes in humans.

Methods

Four potentially functional variants in the coding region of the DRD2/ANKK1 locus (rs1079597, rs6275, rs6277, rs1800497) were genotyped and analysed for Type 2 diabetes susceptibility in up to 25 000 people (8148 with Type 2 diabetes and 17687 control subjects) from two large independent Dutch cohorts and one Danish cohort. In addition, 340 Dutch subjects underwent a 2-h hyperglycaemic clamp to investigate insulin secretion. Since sexual dimorphic associations related to DRD2 polymorphisms have been previously reported, we also performed a gender-stratified analysis.

Results

rs1800497 at the DRD2/ANKK1 locus was associated with a significantly increased risk for Type 2 diabetes in women (odds ratio 1.14 (1.06-1.23); = 4.1*10−4) but not in men (odds ratio 1.00 (95% CI 0.93-1.07); = 0.92) or the combined group. Although rs1800497 was not associated with insulin secretion, we did find another single nucleotide polymorphism in this locus, rs6275, to be associated with increased first-phase glucose-stimulated insulin secretion in women (= 5.5*10−4) but again not in men (= 0.34).

Conclusion

The present data identify DRD2/ANKK1 as a potential sex-specific Type 2 diabetes susceptibility gene.

 
 
 
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