OBJECTIVE - To investigate whether SIRT1, a nutrient-sensing histone deacetylase, influences fetal programming during malnutrition. RESEARCH DESIGN AND 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.

dx.doi.org/10.2337/dc11-1203, hdl.handle.net/1765/68535
Diabetes Care
Department of Internal Medicine

Botden, I.P.G, Danser, A.H.J, Zillikens, M.C, Sijbrands, E.J.G, de Rooij, S.R, Roseboom, T.J, & Langendonk, J.G. (2012). Variants in the SIRT1 gene may affect diabetes risk in interaction with prenatal exposure to famine. Diabetes Care, 35(2), 424–426. doi:10.2337/dc11-1203