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SIRT1 protects cells against oxidative stress and aging. Its activity may be modulated by dietary niacin (vitamin B3) intake. We studied the association of SIRT1 genetic variation with mortality in subjects with increased oxidative stress (type 2 diabetes and smokers) in relation to dietary niacin. In 4573 participants from the Rotterdam Study, including 413 subjects with prevalent and 378 with incident type 2 diabetes, three SIRT1 tagging SNPs were genotyped and all-cause mortality was studied (average follow-up 12 years). We found no association between SIRT1 variation and mortality in the total population or in smokers. In subjects with prevalent type 2 diabetes, homozygous carriers of the most common SIRT1 haplotype, 1, had 1.5 times (95%CI 1.1-2.1) increased mortality risk compared to noncarriers. This risk further increased among smokers and those with low niacin intake. In the lowest tertile of niacin intake, mortality risk was increased 2.3 (95%CI 1.1-4.9) and 5.7 (95%CI 2.5-13.1) times for heterozygous and homozygous carriers of haplotype 1. Subjects with incident diabetes showed similar findings but only when they smoked. We conclude that in subjects with type 2 diabetes, SIRT1 genetic variation influences survival in interaction with dietary niacin and smoking. Correction of niacin deficiency and SIRT1 modulators may prolong the life span of patients with diabetes.

Original publication

DOI

10.1016/j.freeradbiomed.2008.12.022

Type

Journal article

Journal

Free radical biology & medicine

Publication Date

03/2009

Volume

46

Pages

836 - 841

Addresses

Department of Internal Medicine, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands. m.c.zillikens@erasmusmc.nl

Keywords

Humans, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Niacin, Survival Analysis, Cohort Studies, Follow-Up Studies, Smoking, Oxidative Stress, Aging, Cytoprotection, Genotype, Haplotypes, Polymorphism, Single Nucleotide, Dietary Supplements, Aged, Middle Aged, Female, Male, Sirtuin 1