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SIRT1 is associated with a decrease in acute insulin secretion and a sex specific increase in risk for type 2
Yan Dong1, Tingwei Guo, Michael Traurig
1Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
Molecular Genetics and Metabolism
|August 30, 2011
Summary
Genetic variations in SIRT1 are linked to type 2 diabetes risk and reduced insulin response in Pima Indians. SIRT1 expression in adipose tissue correlates with BMI, but its role in obesity remains unclear.
Area of Science:
- Genetics
- Metabolic Diseases
- Obesity Research
Background:
- Genetic variation in SIRT1 is implicated in obesity-related phenotypes.
- Pima Indians exhibit high rates of obesity and type 2 diabetes, making them a key population for study.
Purpose of the Study:
- To investigate the association between SIRT1 gene variation and susceptibility to obesity and type 2 diabetes in Pima Indians.
- To explore the relationship between SIRT1 variation, metabolic traits, and adipose tissue expression.
Main Methods:
- Genotyping of 4 tag SNPs in SIRT1 and its 5' region in 3501 Pima Indians.
- Association analysis with type 2 diabetes and Body Mass Index (BMI).
- Analysis of metabolic traits, insulin response, and adipose SIRT1 expression in subsets.
Main Results:
- Two tag SNPs (rs10509291, rs7896005) showed nominal association with type 2 diabetes risk.
- Carriers of risk alleles for these SNPs had reduced acute insulin response (AIR) in individuals with normal glucose tolerance.
- SIRT1 expression in adipose tissue was negatively correlated with BMI.
Conclusions:
- SIRT1 genetic variation is nominally associated with reduced AIR and increased type 2 diabetes risk.
- SIRT1 adipose expression correlates with BMI, suggesting a potential role in obesity, though causality is undetermined.
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