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The effects of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ2 gene on glucose/insulin metabolism interact with prenatal exposure to famine

The effects of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ2 gene on glucose/insulin metabolism interact with prenatal exposure to famine
The effects of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ2 gene on glucose/insulin metabolism interact with prenatal exposure to famine

OBJECTIVE: An adverse fetal environment may permanently modify the effects of specific genes on glucose tolerance, insulin secretion, and insulin sensitivity. In the present study, we assessed a possible interaction of the peroxisome proliferator-activated receptor (PPAR)-gamma2 Pro12Ala polymorphism with prenatal exposure to famine on glucose and insulin metabolism.

RESEARCH DESIGN AND METHODS: We measured plasma glucose and insulin concentrations after an oral glucose tolerance test and determined the PPAR-gamma2 genotype among 675 term singletons born around the time of the 1944-1945 Dutch famine.

RESULTS: A significant interaction effect between exposure to famine during midgestation and the PPAR-gamma2 Pro12Ala polymorphism was found on the prevalence of impaired glucose tolerance and type 2 diabetes. The Ala allele of the PPAR-gamma2 gene was associated with a higher prevalence of impaired glucose tolerance and type 2 diabetes but only in participants who had been prenatally exposed to famine during midgestation. Similar interactions were found for area under the curve for insulin and insulin increment ratio, which were lower for Ala carriers exposed to famine during midgestation.

CONCLUSIONS: The effects of the PPAR-gamma2 Pro12Ala polymorphism on glucose and insulin metabolism may be modified by prenatal exposure to famine during midgestation. This is possibly due to a combined deficit in insulin secretion, as conferred by pancreatic beta-cell maldevelopment and carrier type of the Ala allele in the PPAR-gamma2 gene.

aged, alanine, blood, blood glucose, design, diabetes, DNA primers, environment, epidemiology, exposure, female, fetal, genetics, genotype, glucose, glucose tolerance, glucose tolerance test, humans, insulin, male, maternal age, metabolism, methods, netherlands, plasma, polymorphism, genetic, PPAR gamma, pregnancy, prenatal exposure delayed effects, prevalence, proline, research support, non-US gov't, starvation, time
1935-5548
1052-1057
de Rooij, Susanne R
d81597b8-478e-406a-b48b-b6700e52b467
Painter, Rebecca C
9c48514b-b4e8-438a-940c-bbfc7e11a1ac
Phillips, David I W
29b73be7-2ff9-4fff-ae42-d59842df4cc6
Osmond, Clive
2677bf85-494f-4a78-adf8-580e1b8acb81
Tanck, Michael W T
1bc26c04-df90-4691-82cc-788faefade37
Defesche, Joep C
827a5a75-cb78-4298-b456-d33e979125e4
Bossuyt, Patrick M M
8a2ec9f4-db0d-40e7-9592-363cf379bd4c
Michels, Robert P J
f5e8137e-7c8e-435b-b37f-352c7abc78f1
Bleker, Otto P
047c2fa6-5b66-4c7b-98a9-51ed4a1e3b08
Roseboom, Tessa J
ca016399-99d7-4918-9572-e3d37d20f1b6
de Rooij, Susanne R
d81597b8-478e-406a-b48b-b6700e52b467
Painter, Rebecca C
9c48514b-b4e8-438a-940c-bbfc7e11a1ac
Phillips, David I W
29b73be7-2ff9-4fff-ae42-d59842df4cc6
Osmond, Clive
2677bf85-494f-4a78-adf8-580e1b8acb81
Tanck, Michael W T
1bc26c04-df90-4691-82cc-788faefade37
Defesche, Joep C
827a5a75-cb78-4298-b456-d33e979125e4
Bossuyt, Patrick M M
8a2ec9f4-db0d-40e7-9592-363cf379bd4c
Michels, Robert P J
f5e8137e-7c8e-435b-b37f-352c7abc78f1
Bleker, Otto P
047c2fa6-5b66-4c7b-98a9-51ed4a1e3b08
Roseboom, Tessa J
ca016399-99d7-4918-9572-e3d37d20f1b6

de Rooij, Susanne R, Painter, Rebecca C, Phillips, David I W, Osmond, Clive, Tanck, Michael W T, Defesche, Joep C, Bossuyt, Patrick M M, Michels, Robert P J, Bleker, Otto P and Roseboom, Tessa J (2006) The effects of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ2 gene on glucose/insulin metabolism interact with prenatal exposure to famine. Diabetes Care, 29 (5), 1052-1057. (doi:10.2337/diacare.2951052).

Record type: Article

Abstract

OBJECTIVE: An adverse fetal environment may permanently modify the effects of specific genes on glucose tolerance, insulin secretion, and insulin sensitivity. In the present study, we assessed a possible interaction of the peroxisome proliferator-activated receptor (PPAR)-gamma2 Pro12Ala polymorphism with prenatal exposure to famine on glucose and insulin metabolism.

RESEARCH DESIGN AND METHODS: We measured plasma glucose and insulin concentrations after an oral glucose tolerance test and determined the PPAR-gamma2 genotype among 675 term singletons born around the time of the 1944-1945 Dutch famine.

RESULTS: A significant interaction effect between exposure to famine during midgestation and the PPAR-gamma2 Pro12Ala polymorphism was found on the prevalence of impaired glucose tolerance and type 2 diabetes. The Ala allele of the PPAR-gamma2 gene was associated with a higher prevalence of impaired glucose tolerance and type 2 diabetes but only in participants who had been prenatally exposed to famine during midgestation. Similar interactions were found for area under the curve for insulin and insulin increment ratio, which were lower for Ala carriers exposed to famine during midgestation.

CONCLUSIONS: The effects of the PPAR-gamma2 Pro12Ala polymorphism on glucose and insulin metabolism may be modified by prenatal exposure to famine during midgestation. This is possibly due to a combined deficit in insulin secretion, as conferred by pancreatic beta-cell maldevelopment and carrier type of the Ala allele in the PPAR-gamma2 gene.

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More information

Published date: 15 May 2006
Keywords: aged, alanine, blood, blood glucose, design, diabetes, DNA primers, environment, epidemiology, exposure, female, fetal, genetics, genotype, glucose, glucose tolerance, glucose tolerance test, humans, insulin, male, maternal age, metabolism, methods, netherlands, plasma, polymorphism, genetic, PPAR gamma, pregnancy, prenatal exposure delayed effects, prevalence, proline, research support, non-US gov't, starvation, time

Identifiers

Local EPrints ID: 44227
URI: http://eprints.soton.ac.uk/id/eprint/44227
ISSN: 1935-5548
PURE UUID: dfdc6527-803c-49a0-b20e-3404248278a6
ORCID for Clive Osmond: ORCID iD orcid.org/0000-0002-9054-4655

Catalogue record

Date deposited: 20 Feb 2007
Last modified: 24 Oct 2024 01:34

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Contributors

Author: Susanne R de Rooij
Author: Rebecca C Painter
Author: David I W Phillips
Author: Clive Osmond ORCID iD
Author: Michael W T Tanck
Author: Joep C Defesche
Author: Patrick M M Bossuyt
Author: Robert P J Michels
Author: Otto P Bleker
Author: Tessa J Roseboom

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