Sex-specific effects of naturally occurring variants in the dopamine receptor D2 locus on insulin secretion and Type 2 diabetes susceptibility

B. Guigas; J. de Leeuw van Weenen; N. van Leeuwen; A.M.C. Bik-Simonis; 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. Jørgensen; D.R. Witte; T. Lauritzen; T. Hansen; O. Pedersen; J.J. Hottenga; J.A. Romijn; M. Diamant; M.H.H. Kramer; R.J. Heine; G. Willemsen; J.M. Dekker; E.M.W. Eekhoff; H. Pijl; E.J.C. de Geus; P.E. Slagboom; L.M. 't Hart

doi:10.1111/dme.12464

Sex-specific effects of naturally occurring variants in the dopamine receptor D2 locus on insulin secretion and Type 2 diabetes susceptibility

B. Guigas
, J. de Leeuw van Weenen
, N. van Leeuwen
, A.M.C. Bik-Simonis
, 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. Jørgensen
, D.R. Witte

T. Lauritzen, T. Hansen, O. Pedersen, J.J. Hottenga, J.A. Romijn, M. Diamant, M.H.H. Kramer, R.J. Heine, G. Willemsen, J.M. Dekker, E.M.W. Eekhoff, H. Pijl, E.J.C. de Geus, P.E. Slagboom, L.M. 't Hart

Biological Psychology

Research output: Contribution to Journal › Article › Academic › peer-review

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

Original language	English
Pages (from-to)	1001-1008
Number of pages	8
Journal	Diabetic Medicine
Volume	31
Issue number	8
DOIs	https://doi.org/10.1111/dme.12464
Publication status	Published - 2014

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.1111/dme.12464

http://www.tweelingenregister.org/publicaties

Persistent URL (handle)

Persistent link

Cite this

Guigas, B., de Leeuw van Weenen, J., van Leeuwen, N., Bik-Simonis, A. M. C., 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., ... '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, 31(8), 1001-1008. https://doi.org/10.1111/dme.12464

@article{b39d3cdcc3f945baa81a0252e45c0d6e,

title = "Sex-specific effects of naturally occurring variants in the dopamine receptor D2 locus on insulin secretion and Type 2 diabetes susceptibility",

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",

author = "B. Guigas and \{de Leeuw van Weenen\}, J. and \{van Leeuwen\}, N. and A.M.C. Bik-Simonis and \{van Haeften\}, T.W. and G. Nijpels and J.J. Houwing-Duistermaat and M. Beekman and J. Deelen and L.M. Havekes and B.W.J.H. Penninx and N. Vogelzangs and \{van 't Riet\}, E. and A. Dehghan and A. Hofman and J.C. Witteman and A.G. Uitterlinden and N. Grarup and T. J{\o}rgensen and D.R. Witte and T. Lauritzen and T. Hansen and O. Pedersen and J.J. Hottenga and J.A. Romijn and M. Diamant and M.H.H. Kramer and R.J. Heine and G. Willemsen and J.M. Dekker and E.M.W. Eekhoff and H. Pijl and \{de Geus\}, E.J.C. and P.E. Slagboom and \{'t Hart\}, L.M.",

year = "2014",

doi = "10.1111/dme.12464",

language = "English",

volume = "31",

pages = "1001--1008",

journal = "Diabetic Medicine",

issn = "0742-3071",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "8",

}

Guigas, B, de Leeuw van Weenen, J, van Leeuwen, N, Bik-Simonis, AMC, van Haeften, TW, Nijpels, G, Houwing-Duistermaat, JJ, Beekman, M, Deelen, J, Havekes, LM, Penninx, BWJH, Vogelzangs, N, van 't Riet, E, Dehghan, A, Hofman, A, Witteman, JC, Uitterlinden, AG, Grarup, N, Jørgensen, T, Witte, DR, Lauritzen, T, Hansen, T, Pedersen, O, Hottenga, JJ, Romijn, JA, Diamant, M, Kramer, MHH, Heine, RJ, Willemsen, G, Dekker, JM, Eekhoff, EMW, Pijl, H, de Geus, EJC, Slagboom, PE & 't Hart, LM 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. 1001-1008. https://doi.org/10.1111/dme.12464

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.

AU - van Leeuwen, N.

AU - Bik-Simonis, A.M.C.

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, N.

AU - Jørgensen, T.

AU - Witte, D.R.

AU - Lauritzen, T.

AU - Hansen, T.

AU - Pedersen, O.

AU - Hottenga, J.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.W.

AU - Pijl, H.

AU - de Geus, E.J.C.

AU - Slagboom, P.E.

AU - 't Hart, L.M.

PY - 2014

Y1 - 2014

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

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

U2 - 10.1111/dme.12464

DO - 10.1111/dme.12464

M3 - Article

SN - 0742-3071

VL - 31

SP - 1001

EP - 1008

JO - Diabetic Medicine

JF - Diabetic Medicine

IS - 8

ER -

Sex-specific effects of naturally occurring variants in the dopamine receptor D2 locus on insulin secretion and Type 2 diabetes susceptibility

Abstract

UN SDGs

Access to Document

Persistent URL (handle)

Fingerprint

Cite this