Variants in the SIRT1 gene may affect diabetes risk in interaction with prenatal exposure to famine.
OBJECTIVE
To investigate whether SIRT1, a nutrient-sensing histone deacetylase, influences fetal programming during malnutrition.


METHODS
In 793 individuals of the Dutch Famine Birth Cohort, we analyzed the interaction between three SIRT1 single nucleotide polymorphisms (SNPs) and prenatal exposure to famine on type 2 diabetes risk.


RESULTS
In the total population (exposed and unexposed), SIRT1 variants were not associated with type 2 diabetes. A significant interaction was found between two SIRT1 SNPs and exposure to famine in utero on type 2 diabetes risk (P = 0.03 for rs7895833; P = 0.01 for rs1467568). Minor alleles of these SNPs were associated with a lower prevalence of type 2 diabetes only in individuals who had been exposed to famine prenatally (odds ratio for rs7895833 0.50 [95% CI 0.24-1.03], P = 0.06; for rs1467568 0.48 [0.25-0.91], P = 0.02).


CONCLUSIONS
SIRT1 may be an important genetic factor involved in fetal programming during malnutrition, influencing type 2 diabetes risk later in life.
Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
Ilse P G
IP
Botden
M Carola
MC
Zillikens
Susanne R
SR
de Rooij
Janneke G
JG
Langendonk
A H Jan
AH
Danser
Eric J G
EJ
Sijbrands
Tessa J
TJ
Roseboom
D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D044342:Malnutrition / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics; D056564:Sirtuin 1 / Q000235:genetics*
C447939:SIRT1 protein, human; D056564:Sirtuin 1