Sex-specific effects of naturally occurring variants in the dopamine receptor D2 locus on insulin secretion and Type 2 diabetes susceptibility
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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. / 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, Niels; Jørgensen, Torben; Witte, D R; Lauritzen, T; Hansen, Torben; 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.
In: Diabetic Medicine, Vol. 31, No. 8, 08.2014, p. 1001-8.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Sex-specific effects of naturally occurring variants in the dopamine receptor D2 locus on insulin secretion and Type 2 diabetes susceptibility
AU - Guigas, B
AU - de Leeuw van Weenen, J E
AU - van Leeuwen, N
AU - Simonis-Bik, A M
AU - van Haeften, T W
AU - Nijpels, G
AU - Houwing-Duistermaat, J J
AU - Beekman, M
AU - Deelen, J
AU - Havekes, L M
AU - Penninx, B W J H
AU - Vogelzangs, N
AU - van 't Riet, E
AU - Dehghan, A
AU - Hofman, A
AU - Witteman, J C
AU - Uitterlinden, A G
AU - Grarup, Niels
AU - Jørgensen, Torben
AU - Witte, D R
AU - Lauritzen, T
AU - Hansen, Torben
AU - Pedersen, O
AU - Hottenga, J
AU - Romijn, J A
AU - Diamant, M
AU - Kramer, M H H
AU - Heine, R J
AU - Willemsen, G
AU - Dekker, J M
AU - Eekhoff, E M
AU - Pijl, H
AU - de Geus, E J
AU - Slagboom, P E
AU - 't Hart, L M
N1 - © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
U2 - 10.1111/dme.12464
DO - 10.1111/dme.12464
M3 - Journal article
C2 - 24724616
VL - 31
SP - 1001
EP - 1008
JO - Diabetic Medicine
JF - Diabetic Medicine
SN - 0742-3071
IS - 8
ER -
ID: 120783562