The hormone-sensitive lipase C-60G promoter polymorphism is associated with increased waist circumference in normal-weight subjects.
Author
Summary, in English
OBJECTIVE: Hormone-sensitive lipase (HSL) is a key enzyme in the mobilization of fatty acids from triglyceride stores in adipocytes. The aim of the present study was to investigate the role of the HSL gene promoter variant C-60G, a polymorphism which previously has been associated with reduced promoter activity in vitro, in obesity and type 2 diabetes. DESIGN: We genotyped two materials consisting of obese subjects and non-obese controls, one material with offspring-parents trios, where the offspring was abdominally obese and one material with trios, where the offspring had type 2 diabetes or impaired glucose homeostasis. HSL promoter containing the HSL C-60G G-allele was generated and tested against a construct with the C-allele in HeLa cells and primary rat adipocytes. HSL mRNA levels were quantified in subcutaneous and visceral fat from 33 obese subjects. RESULTS: We found that the common C-allele was associated with increased waist circumference and WHR in lean controls, but there was no difference in genotype frequency between obese and non-obese subjects. There was a significant increased transmission of C-alleles to the abdominally obese offspring but no increased transmission of C-alleles was observed to offspring with impaired glucose homeostasis. The G-allele showed reduced transcription in HeLa cells and primary rat adipocytes. HSL mRNA levels were significantly higher in subcutaneous compared to visceral fat from obese subjects. CONCLUSION: The HSL C-60G polymorphism is associated with increased waist circumference in non-obese subjects.
Department/s
- Translational Muscle Research
- Diabetes - Epigenetics
- Molecular Endocrinology
- Diabetes - Clinical Obesity
Publishing year
2006
Language
English
Pages
1442-1448
Publication/Series
International Journal of Obesity
Volume
30
Issue
9
Links
Document type
Journal article
Publisher
Nature Publishing Group
Topic
- Nutrition and Dietetics
Keywords
- transmission
- case-control association study
- hormone-sensitive lipase
- disequilibrium test
- adipose tissue
Status
Published
Research group
- Genomics, Diabetes and Endocrinology
- Diabetes - Epigenetics
- Molecular Endocrinology
- Diabetes - Clinical Obesity
ISBN/ISSN/Other
- ISSN: 1476-5497