The effects of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 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.


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.
de Rooij
Susanne R
SR
Academic Medical Centre, Department of Clinical Epidemiology and Biostatistics, Room nr J1B-210-1, Meibergdreef 9, P.O. Box 22660, 1100 DD, Amsterdam, Netherlands. s.r.derooij@amc.uva.nl
Painter
Rebecca C
RC
Phillips
David I W
DI
Osmond
Clive
C
Tanck
Michael W T
MW
Defesche
Joep C
JC
Bossuyt
Patrick M M
PM
Michels
Robert P J
RP
Bleker
Otto P
OP
Roseboom
Tessa J
TJ
D000368:Aged; D000409:Alanine; D001786:Blood Glucose / Q000378:metabolism; D017931:DNA Primers; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D008423:Maternal Age; D009426:Netherlands; D047495:PPAR gamma / Q000235:genetics*; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011392:Proline; D013217:Starvation
D001786:Blood Glucose; D017931:DNA Primers; D007328:Insulin; D047495:PPAR gamma; D011392:Proline; D000409:Alanine