SIRT1 is associated with a decrease in acute insulin secretion and a sex specific increase in risk for type 2 diabetes in Pima Indians

Yan Dong, Tingwei Guo, Michael Traurig, Clint C. Mason, Sayuko Kobes, Jessica Perez, William C. Knowler, Clifton Bogardus, Robert L. Hanson, Leslie J. Baier

Research output: Contribution to journalArticle

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Abstract

Genetic variation in SIRT1 affects obesity-related phenotypes in several populations. The purpose of this study was to determine whether variation in SIRT1 affects susceptibility to obesity or type 2 diabetes in Pima Indians, a population with very high prevalence and incidence rates of these diseases. Genotypic data from single nucleotide polymorphisms (SNPs) identified by sequencing regions of SIRT1 combined with SNPs in/near SIRT1 from a prior genome-wide association study determined that 4 tag SNPs (rs7895833, rs10509291, rs7896005, and rs4746720) could capture information across this gene and its adjacent 5' region. The tag SNPs were genotyped in a population-based sample of 3501 Pima Indians (44% had diabetes, 58% female) for association with type 2 diabetes and BMI. Metabolic trait data and adipose biopsies were available on a subset of these subjects. Two tag SNPs, rs10509291 and rs7896005, were nominally associated with type 2 diabetes (P= 0.01, OR = 1.25 95%CI 1.05-1.48, and P= 0.02, OR = 1.17 95%CI 1.02-1.34, respectively; additive P values adjusted for age, sex, birth year, and family membership), but not BMI (adjusted P values 0.52 and 0.45, respectively). Among metabolically characterized subjects with normal glucose tolerance (N = 243), those carrying the diabetes risk allele (T) for rs10509291 and (G) for rs7896005 had a reduced acute insulin response (AIR) to an intravenous glucose bolus (adjusted P= 0.045 and 0.035, respectively). SIRT1 expression in adipose biopsies was negatively correlated with BMI (adjusted P= 0.00001). We conclude that variation in SIRT1 is nominally associated with reduced AIR and increased risk for type 2 diabetes. SIRT1 expression in adipose is correlated with BMI, but it remains unknown whether this is a cause or consequence of obesity.

Original languageEnglish (US)
Pages (from-to)661-665
Number of pages5
JournalMolecular Genetics and Metabolism
Volume104
Issue number4
DOIs
StatePublished - Dec 2011
Externally publishedYes

Fingerprint

Potassium Iodide
Medical problems
Type 2 Diabetes Mellitus
Single Nucleotide Polymorphism
Polymorphism
Insulin
Nucleotides
Obesity
Biopsy
Population
Glucose
Genes
Genome-Wide Association Study
Alleles
Parturition
Phenotype
Incidence

Keywords

  • Genetic associations
  • Insulin secretion
  • SIRT1
  • Type 2 diabetes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

SIRT1 is associated with a decrease in acute insulin secretion and a sex specific increase in risk for type 2 diabetes in Pima Indians. / Dong, Yan; Guo, Tingwei; Traurig, Michael; Mason, Clint C.; Kobes, Sayuko; Perez, Jessica; Knowler, William C.; Bogardus, Clifton; Hanson, Robert L.; Baier, Leslie J.

In: Molecular Genetics and Metabolism, Vol. 104, No. 4, 12.2011, p. 661-665.

Research output: Contribution to journalArticle

Dong, Y, Guo, T, Traurig, M, Mason, CC, Kobes, S, Perez, J, Knowler, WC, Bogardus, C, Hanson, RL & Baier, LJ 2011, 'SIRT1 is associated with a decrease in acute insulin secretion and a sex specific increase in risk for type 2 diabetes in Pima Indians', Molecular Genetics and Metabolism, vol. 104, no. 4, pp. 661-665. https://doi.org/10.1016/j.ymgme.2011.08.001
Dong, Yan ; Guo, Tingwei ; Traurig, Michael ; Mason, Clint C. ; Kobes, Sayuko ; Perez, Jessica ; Knowler, William C. ; Bogardus, Clifton ; Hanson, Robert L. ; Baier, Leslie J. / SIRT1 is associated with a decrease in acute insulin secretion and a sex specific increase in risk for type 2 diabetes in Pima Indians. In: Molecular Genetics and Metabolism. 2011 ; Vol. 104, No. 4. pp. 661-665.
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AU - Perez, Jessica

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