The common SLC30A8 Arg325Trp variant is associated with reduced first-phase insulin release in 846 non-diabetic offspring of type 2 diabetes patients--the EUGENE2 study

T W Boesgaard; J Zilinskaite; M Vänttinen; M Laakso; P-A Jansson; A Hammarstedt; U Smith; N Stefan; A Fritsche; H Häring; M Hribal; G Sesti; D P Zobel; Oluf Pedersen; T Hansen; EUGENE 2 Consortium

doi:10.1007/s00125-008-0955-6

The common SLC30A8 Arg325Trp variant is associated with reduced first-phase insulin release in 846 non-diabetic offspring of type 2 diabetes patients--the EUGENE2 study

T W Boesgaard, J Zilinskaite, M Vänttinen, M Laakso, P-A Jansson, A Hammarstedt, U Smith, N Stefan, A Fritsche, H Häring, M Hribal, G Sesti, D P Zobel, Oluf Pedersen, T Hansen, EUGENE 2 Consortium

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

113 Citationer (Scopus)

Abstract

Udgivelsesdato: 2008-May

Originalsprog	Engelsk
Tidsskrift	Diabetologia
Vol/bind	51
Udgave nummer	5
Sider (fra-til)	816-20
Antal sider	4
ISSN	0012-186X
DOI	https://doi.org/10.1007/s00125-008-0955-6
Status	Udgivet - 2008

Bibliografisk note

Keywords: Adult; Amino Acid Substitution; Carrier State; Cation Transport Proteins; Diabetes Mellitus, Type 2; Female; Genotype; Homozygote; Humans; Insulin; Male; Middle Aged; Nuclear Family; Reference Values

Adgang til dokumentet

10.1007/s00125-008-0955-6

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Citationsformater

Boesgaard, T. W., Zilinskaite, J., Vänttinen, M., Laakso, M., Jansson, P.-A., Hammarstedt, A., Smith, U., Stefan, N., Fritsche, A., Häring, H., Hribal, M., Sesti, G., Zobel, D. P., Pedersen, O., Hansen, T., & EUGENE 2 Consortium (2008). The common SLC30A8 Arg325Trp variant is associated with reduced first-phase insulin release in 846 non-diabetic offspring of type 2 diabetes patients--the EUGENE2 study. Diabetologia, 51(5), 816-20. https://doi.org/10.1007/s00125-008-0955-6

Boesgaard, TW, Zilinskaite, J, Vänttinen, M, Laakso, M, Jansson, P-A, Hammarstedt, A, Smith, U, Stefan, N, Fritsche, A, Häring, H, Hribal, M, Sesti, G, Zobel, DP, Pedersen, O , Hansen, T & EUGENE 2 Consortium 2008, 'The common SLC30A8 Arg325Trp variant is associated with reduced first-phase insulin release in 846 non-diabetic offspring of type 2 diabetes patients--the EUGENE2 study', Diabetologia, bind 51, nr. 5, s. 816-20. https://doi.org/10.1007/s00125-008-0955-6

@article{c090dda0eedf11ddbf70000ea68e967b,

title = "The common SLC30A8 Arg325Trp variant is associated with reduced first-phase insulin release in 846 non-diabetic offspring of type 2 diabetes patients--the EUGENE2 study",

abstract = "AIMS/HYPOTHESIS: A recent genome-wide association study identified the SLC30A8 rs13266634 polymorphism encoding an Arg325Trp polymorphism in the zinc transporter protein member 8 (ZnT-8) to be associated with type 2 diabetes. Here, we investigate whether the polymorphism is related to altered insulin release in response to intravenous and oral glucose loads in non-diabetic offspring of type 2 diabetic patients. METHODS: We genotyped SLC30A8 rs13266634 in 846 non-diabetic offspring of type 2 diabetic patients from five different white populations: Danish (n = 271), Finnish (n = 217), German (n = 149), Italian (n = 109) and Swedish (n = 100). Participants were subjected to both IVGTTs and OGTTs, and measurements of insulin sensitivity. RESULTS: Homozygous carriers of the major type 2 diabetes C risk-allele showed a 19% decrease in first-phase insulin release (0-10 min) measured during the IVGTT (CC 3,624 +/- 3,197; CT 3,763 +/- 2,674; TT 4,478 +/- 3,032 pmol l(-1) min(-1), mean +/- SD; p = 0.007). We found no significant genotype effect on insulin release measured during the OGTT or on estimates of insulin sensitivity. CONCLUSIONS/INTERPRETATION: Of European non-diabetic offspring of type 2 diabetes patients, 46% are homozygous carriers of the Arg325Trp polymorphism in ZnT-8, which is known to associate with type 2 diabetes. These diabetes-prone offspring are characterised by a 19% decrease in first-phase insulin release following an intravenous glucose load, suggesting a role for this variant in the pathogenesis of pancreatic beta cell dysfunction.",

author = "Boesgaard, {T W} and J Zilinskaite and M V{\"a}nttinen and M Laakso and P-A Jansson and A Hammarstedt and U Smith and N Stefan and A Fritsche and H H{\"a}ring and M Hribal and G Sesti and Zobel, {D P} and Oluf Pedersen and T Hansen and {EUGENE 2 Consortium}",

note = "Keywords: Adult; Amino Acid Substitution; Carrier State; Cation Transport Proteins; Diabetes Mellitus, Type 2; Female; Genotype; Homozygote; Humans; Insulin; Male; Middle Aged; Nuclear Family; Reference Values",

year = "2008",

doi = "10.1007/s00125-008-0955-6",

language = "English",

volume = "51",

pages = "816--20",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer",

number = "5",

}

TY - JOUR

T1 - The common SLC30A8 Arg325Trp variant is associated with reduced first-phase insulin release in 846 non-diabetic offspring of type 2 diabetes patients--the EUGENE2 study

AU - Boesgaard, T W

AU - Zilinskaite, J

AU - Vänttinen, M

AU - Laakso, M

AU - Jansson, P-A

AU - Hammarstedt, A

AU - Smith, U

AU - Stefan, N

AU - Fritsche, A

AU - Häring, H

AU - Hribal, M

AU - Sesti, G

AU - Zobel, D P

AU - Pedersen, Oluf

AU - Hansen, T

AU - EUGENE 2 Consortium

N1 - Keywords: Adult; Amino Acid Substitution; Carrier State; Cation Transport Proteins; Diabetes Mellitus, Type 2; Female; Genotype; Homozygote; Humans; Insulin; Male; Middle Aged; Nuclear Family; Reference Values

PY - 2008

Y1 - 2008

N2 - AIMS/HYPOTHESIS: A recent genome-wide association study identified the SLC30A8 rs13266634 polymorphism encoding an Arg325Trp polymorphism in the zinc transporter protein member 8 (ZnT-8) to be associated with type 2 diabetes. Here, we investigate whether the polymorphism is related to altered insulin release in response to intravenous and oral glucose loads in non-diabetic offspring of type 2 diabetic patients. METHODS: We genotyped SLC30A8 rs13266634 in 846 non-diabetic offspring of type 2 diabetic patients from five different white populations: Danish (n = 271), Finnish (n = 217), German (n = 149), Italian (n = 109) and Swedish (n = 100). Participants were subjected to both IVGTTs and OGTTs, and measurements of insulin sensitivity. RESULTS: Homozygous carriers of the major type 2 diabetes C risk-allele showed a 19% decrease in first-phase insulin release (0-10 min) measured during the IVGTT (CC 3,624 +/- 3,197; CT 3,763 +/- 2,674; TT 4,478 +/- 3,032 pmol l(-1) min(-1), mean +/- SD; p = 0.007). We found no significant genotype effect on insulin release measured during the OGTT or on estimates of insulin sensitivity. CONCLUSIONS/INTERPRETATION: Of European non-diabetic offspring of type 2 diabetes patients, 46% are homozygous carriers of the Arg325Trp polymorphism in ZnT-8, which is known to associate with type 2 diabetes. These diabetes-prone offspring are characterised by a 19% decrease in first-phase insulin release following an intravenous glucose load, suggesting a role for this variant in the pathogenesis of pancreatic beta cell dysfunction.

AB - AIMS/HYPOTHESIS: A recent genome-wide association study identified the SLC30A8 rs13266634 polymorphism encoding an Arg325Trp polymorphism in the zinc transporter protein member 8 (ZnT-8) to be associated with type 2 diabetes. Here, we investigate whether the polymorphism is related to altered insulin release in response to intravenous and oral glucose loads in non-diabetic offspring of type 2 diabetic patients. METHODS: We genotyped SLC30A8 rs13266634 in 846 non-diabetic offspring of type 2 diabetic patients from five different white populations: Danish (n = 271), Finnish (n = 217), German (n = 149), Italian (n = 109) and Swedish (n = 100). Participants were subjected to both IVGTTs and OGTTs, and measurements of insulin sensitivity. RESULTS: Homozygous carriers of the major type 2 diabetes C risk-allele showed a 19% decrease in first-phase insulin release (0-10 min) measured during the IVGTT (CC 3,624 +/- 3,197; CT 3,763 +/- 2,674; TT 4,478 +/- 3,032 pmol l(-1) min(-1), mean +/- SD; p = 0.007). We found no significant genotype effect on insulin release measured during the OGTT or on estimates of insulin sensitivity. CONCLUSIONS/INTERPRETATION: Of European non-diabetic offspring of type 2 diabetes patients, 46% are homozygous carriers of the Arg325Trp polymorphism in ZnT-8, which is known to associate with type 2 diabetes. These diabetes-prone offspring are characterised by a 19% decrease in first-phase insulin release following an intravenous glucose load, suggesting a role for this variant in the pathogenesis of pancreatic beta cell dysfunction.

U2 - 10.1007/s00125-008-0955-6

DO - 10.1007/s00125-008-0955-6

M3 - Journal article

C2 - 18324385

SN - 0012-186X

VL - 51

SP - 816

EP - 820

JO - Diabetologia

JF - Diabetologia

IS - 5

ER -