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Sex-specific effects of naturally occurring variants in the dopamine receptor D2 locus on insulin secretion and Type 2 diabetes susceptibility
- Source :
- Guigas , B , de Leeuw van Weenen , J E , van Leeuwen , N , Simonis-Bik , A M , van Haeften , T W , Nijpels , G , Houwing-Duistermaat , J J , Beekman , M , Deelen , J , Havekes , L M , Penninx , B W J H , Vogelzangs , N , van 't Riet , E , Dehghan , A , Hofman , A , Witteman , J C , Uitterlinden , A G , Grarup , N , Jørgensen , T , Witte , D R , Lauritzen , T , Hansen , T , Pedersen , O , Hottenga , J , Romijn , J A , Diamant , M , Kramer , M H H , Heine , R J , Willemsen , G , Dekker , J M , Eekhoff , E M , Pijl , H , de Geus , E J , Slagboom , P E & 't Hart , L M 2014 , ' Sex-specific effects of naturally occurring variants in the dopamine receptor D2 locus on insulin secretion and Type 2 diabetes susceptibility ' , Diabetic Medicine , vol. 31 , no. 8 , pp. 1001-8 .
- Publication Year :
- 2014
-
Abstract
- 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); P = 4.1*10(-4) ) but not in men (odds ratio 1.00 (95% CI 0.93-1.07); P = 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 (P = 5.5*10(-4) ) but again not in men (P = 0.34).CONCLUSION: The present data identify DRD2/ANKK1 as a potential sex-specific Type 2 diabetes susceptibility gene.
Details
- Database :
- OAIster
- Journal :
- Guigas , B , de Leeuw van Weenen , J E , van Leeuwen , N , Simonis-Bik , A M , van Haeften , T W , Nijpels , G , Houwing-Duistermaat , J J , Beekman , M , Deelen , J , Havekes , L M , Penninx , B W J H , Vogelzangs , N , van 't Riet , E , Dehghan , A , Hofman , A , Witteman , J C , Uitterlinden , A G , Grarup , N , Jørgensen , T , Witte , D R , Lauritzen , T , Hansen , T , Pedersen , O , Hottenga , J , Romijn , J A , Diamant , M , Kramer , M H H , Heine , R J , Willemsen , G , Dekker , J M , Eekhoff , E M , Pijl , H , de Geus , E J , Slagboom , P E & 't Hart , L M 2014 , ' Sex-specific effects of naturally occurring variants in the dopamine receptor D2 locus on insulin secretion and Type 2 diabetes susceptibility ' , Diabetic Medicine , vol. 31 , no. 8 , pp. 1001-8 .
- Notes :
- English
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.ocn937366596
- Document Type :
- Electronic Resource