Impact of PTBP1 rs11085226 on glucose-stimulated insulin release in adult Danes

Tue Haldor Hansen; Henrik Vestergaard; Torben Jørgensen; Marit Eika Jørgensen; Torsten Lauritzen; Ivan Brandslund; Cramer Christensen; Oluf Borbye Pedersen; Torben Hansen; Anette Marianne Prior Gjesing

doi:10.1186/s12881-015-0160-7

Impact of PTBP1 rs11085226 on glucose-stimulated insulin release in adult Danes

Tue Haldor Hansen, Henrik Vestergaard, Torben Jørgensen, Marit Eika Jørgensen, Torsten Lauritzen, Ivan Brandslund, Cramer Christensen, Oluf Borbye Pedersen, Torben Hansen, Anette Marianne Prior Gjesing

Department of Public Health

1 Citation (Scopus)

Abstract

Background: The variant rs11085226 (G) within the gene encoding polypyrimidine tract binding protein 1 (PTBP1) was reported to associate with reduced insulin release determined by an oral glucose tolerance test (OGTT) as well as an intravenous glucose tolerance test (IVGTT). The aim of the present study was to validate the association of the rs11085226 G-allele of PTBP1 with previously investigated OGTT- and IVGTT-derived diabetes-related metabolic quantitative phenotypes, to conduct exploratory analyses of additional measures of beta-cell function, and to further investigate a potential association with type 2 diabetes. Methods: PTBP1 rs11085226 was genotyped in 20,911 individuals of Danish Caucasian ethnicity ascertained from 9 study samples. Case control analysis was performed on 5,634 type 2 diabetic patients and 11,319 individuals having a normal fasting glucose level as well as 4,641 glucose tolerant controls, respectively. Quantitative trait analyses were performed in up to 13,605 individuals subjected to an OGTT or blood samples obtained after an overnight fast, as well as in 596 individuals subjected to an IVGTT. Results: Analyses of fasting and OGTT-derived quantitative traits did not show any significant associations with the PTBP1 rs11085226 variant. Meta-analysis of IVGTT-derived quantitative traits showed a nominally significant association between the variant and reduced beta-cell responsiveness to glucose (β=-0.1 mmol.kg<sup>-1</sup>.min<sup>-1</sup>; 95% CI: -0.200.20 - -0.024; P=0.01) assuming a dominant model of inheritance, but failed to replicate a previously reported association with area under the curve (AUC) for insulin. Case control analysis did not show an association of the PTBP1 rs11085226 variant with type 2 diabetes. Conclusions: Despite failure to replicate the previously reported associations of PTBP1 rs11085226 with OGTT- and IVGTT-derived measures of beta-cell function, we did find a nominally significant association with reduced beta-cell responsiveness to glucose during an IVGTT, a trait not previously investigated, leaving the potential influence of this variant in PTBP1 on glucose stimulated insulin release open for further investigation. However, the present study does not support the hypothesis that the variant confers risk of type 2 diabetes.

Original language	English
Article number	17
Journal	BMC Medical Genetics
Volume	16
Pages (from-to)	1-9
Number of pages	9
ISSN	1471-2350
DOIs	https://doi.org/10.1186/s12881-015-0160-7
Publication status	Published - 20 Mar 2015

Keywords

Beta-cell function
Genetics
Insulin release
Polypyrimidine tract binding protein 1
Type 2 diabetes

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10.1186/s12881-015-0160-7

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@article{540f6bde9d154c5a925afb0c1929bd91,

title = "Impact of PTBP1 rs11085226 on glucose-stimulated insulin release in adult Danes",

abstract = "Background: The variant rs11085226 (G) within the gene encoding polypyrimidine tract binding protein 1 (PTBP1) was reported to associate with reduced insulin release determined by an oral glucose tolerance test (OGTT) as well as an intravenous glucose tolerance test (IVGTT). The aim of the present study was to validate the association of the rs11085226 G-allele of PTBP1 with previously investigated OGTT- and IVGTT-derived diabetes-related metabolic quantitative phenotypes, to conduct exploratory analyses of additional measures of beta-cell function, and to further investigate a potential association with type 2 diabetes. Methods: PTBP1 rs11085226 was genotyped in 20,911 individuals of Danish Caucasian ethnicity ascertained from 9 study samples. Case control analysis was performed on 5,634 type 2 diabetic patients and 11,319 individuals having a normal fasting glucose level as well as 4,641 glucose tolerant controls, respectively. Quantitative trait analyses were performed in up to 13,605 individuals subjected to an OGTT or blood samples obtained after an overnight fast, as well as in 596 individuals subjected to an IVGTT. Results: Analyses of fasting and OGTT-derived quantitative traits did not show any significant associations with the PTBP1 rs11085226 variant. Meta-analysis of IVGTT-derived quantitative traits showed a nominally significant association between the variant and reduced beta-cell responsiveness to glucose (β=-0.1 mmol.kg-1.min-1; 95% CI: -0.200.20 - -0.024; P=0.01) assuming a dominant model of inheritance, but failed to replicate a previously reported association with area under the curve (AUC) for insulin. Case control analysis did not show an association of the PTBP1 rs11085226 variant with type 2 diabetes. Conclusions: Despite failure to replicate the previously reported associations of PTBP1 rs11085226 with OGTT- and IVGTT-derived measures of beta-cell function, we did find a nominally significant association with reduced beta-cell responsiveness to glucose during an IVGTT, a trait not previously investigated, leaving the potential influence of this variant in PTBP1 on glucose stimulated insulin release open for further investigation. However, the present study does not support the hypothesis that the variant confers risk of type 2 diabetes.",

keywords = "Beta-cell function, Genetics, Insulin release, Polypyrimidine tract binding protein 1, Type 2 diabetes",

author = "Hansen, {Tue Haldor} and Henrik Vestergaard and Torben J{\o}rgensen and J{\o}rgensen, {Marit Eika} and Torsten Lauritzen and Ivan Brandslund and Cramer Christensen and Pedersen, {Oluf Borbye} and Torben Hansen and Gjesing, {Anette Marianne Prior}",

year = "2015",

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day = "20",

doi = "10.1186/s12881-015-0160-7",

language = "English",

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journal = "BMC Medical Genetics",

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T1 - Impact of PTBP1 rs11085226 on glucose-stimulated insulin release in adult Danes

AU - Hansen, Tue Haldor

AU - Vestergaard, Henrik

AU - Jørgensen, Torben

AU - Jørgensen, Marit Eika

AU - Lauritzen, Torsten

AU - Brandslund, Ivan

AU - Christensen, Cramer

AU - Pedersen, Oluf Borbye

AU - Hansen, Torben

AU - Gjesing, Anette Marianne Prior

PY - 2015/3/20

Y1 - 2015/3/20

N2 - Background: The variant rs11085226 (G) within the gene encoding polypyrimidine tract binding protein 1 (PTBP1) was reported to associate with reduced insulin release determined by an oral glucose tolerance test (OGTT) as well as an intravenous glucose tolerance test (IVGTT). The aim of the present study was to validate the association of the rs11085226 G-allele of PTBP1 with previously investigated OGTT- and IVGTT-derived diabetes-related metabolic quantitative phenotypes, to conduct exploratory analyses of additional measures of beta-cell function, and to further investigate a potential association with type 2 diabetes. Methods: PTBP1 rs11085226 was genotyped in 20,911 individuals of Danish Caucasian ethnicity ascertained from 9 study samples. Case control analysis was performed on 5,634 type 2 diabetic patients and 11,319 individuals having a normal fasting glucose level as well as 4,641 glucose tolerant controls, respectively. Quantitative trait analyses were performed in up to 13,605 individuals subjected to an OGTT or blood samples obtained after an overnight fast, as well as in 596 individuals subjected to an IVGTT. Results: Analyses of fasting and OGTT-derived quantitative traits did not show any significant associations with the PTBP1 rs11085226 variant. Meta-analysis of IVGTT-derived quantitative traits showed a nominally significant association between the variant and reduced beta-cell responsiveness to glucose (β=-0.1 mmol.kg-1.min-1; 95% CI: -0.200.20 - -0.024; P=0.01) assuming a dominant model of inheritance, but failed to replicate a previously reported association with area under the curve (AUC) for insulin. Case control analysis did not show an association of the PTBP1 rs11085226 variant with type 2 diabetes. Conclusions: Despite failure to replicate the previously reported associations of PTBP1 rs11085226 with OGTT- and IVGTT-derived measures of beta-cell function, we did find a nominally significant association with reduced beta-cell responsiveness to glucose during an IVGTT, a trait not previously investigated, leaving the potential influence of this variant in PTBP1 on glucose stimulated insulin release open for further investigation. However, the present study does not support the hypothesis that the variant confers risk of type 2 diabetes.

AB - Background: The variant rs11085226 (G) within the gene encoding polypyrimidine tract binding protein 1 (PTBP1) was reported to associate with reduced insulin release determined by an oral glucose tolerance test (OGTT) as well as an intravenous glucose tolerance test (IVGTT). The aim of the present study was to validate the association of the rs11085226 G-allele of PTBP1 with previously investigated OGTT- and IVGTT-derived diabetes-related metabolic quantitative phenotypes, to conduct exploratory analyses of additional measures of beta-cell function, and to further investigate a potential association with type 2 diabetes. Methods: PTBP1 rs11085226 was genotyped in 20,911 individuals of Danish Caucasian ethnicity ascertained from 9 study samples. Case control analysis was performed on 5,634 type 2 diabetic patients and 11,319 individuals having a normal fasting glucose level as well as 4,641 glucose tolerant controls, respectively. Quantitative trait analyses were performed in up to 13,605 individuals subjected to an OGTT or blood samples obtained after an overnight fast, as well as in 596 individuals subjected to an IVGTT. Results: Analyses of fasting and OGTT-derived quantitative traits did not show any significant associations with the PTBP1 rs11085226 variant. Meta-analysis of IVGTT-derived quantitative traits showed a nominally significant association between the variant and reduced beta-cell responsiveness to glucose (β=-0.1 mmol.kg-1.min-1; 95% CI: -0.200.20 - -0.024; P=0.01) assuming a dominant model of inheritance, but failed to replicate a previously reported association with area under the curve (AUC) for insulin. Case control analysis did not show an association of the PTBP1 rs11085226 variant with type 2 diabetes. Conclusions: Despite failure to replicate the previously reported associations of PTBP1 rs11085226 with OGTT- and IVGTT-derived measures of beta-cell function, we did find a nominally significant association with reduced beta-cell responsiveness to glucose during an IVGTT, a trait not previously investigated, leaving the potential influence of this variant in PTBP1 on glucose stimulated insulin release open for further investigation. However, the present study does not support the hypothesis that the variant confers risk of type 2 diabetes.

KW - Beta-cell function

KW - Genetics

KW - Insulin release

KW - Polypyrimidine tract binding protein 1

KW - Type 2 diabetes

U2 - 10.1186/s12881-015-0160-7

DO - 10.1186/s12881-015-0160-7

M3 - Journal article

C2 - 25927630

AN - SCOPUS:84927946420

SN - 1471-2350

VL - 16

SP - 1

EP - 9

JO - BMC Medical Genetics

JF - BMC Medical Genetics

M1 - 17

ER -

Impact of PTBP1 rs11085226 on glucose-stimulated insulin release in adult Danes

Abstract

Keywords

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