The hormone-sensitive lipase C-60G promoter polymorphism is associated with increased waist circumference in normal-weight subjects

• Published in: INTERNATIONAL JOURNAL OF OBESITY 2006-09, Vol.30 (9), p.1442-1448
• Main Authors: Carlsson, E, Johansson, L E, Ström, K, Hoffstedt, J, Groop, L, Holm, C, Ridderstråle, M
• Format: Article
• Language: English
• Subjects: Adipocytes; adipose tissue; Adult; Age; Biological and medical sciences; Body Height; Body Weight; case-control association study; Cohort Studies; Diabetes; Diabetes Mellitus, Type 2 - genetics; disequilibrium test; Endocrinology; Enzymes; Epidemiology; Fatty acids; Female; Gastrointestinal surgery; Genotype; Glucose; Health Promotion and Disease Prevention; Health Sciences; Homeostasis; hormone-sensitive lipase; Humans; Hälsovetenskap; Internal Medicine; Male; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolism; Middle Aged; Nutrition and Dietetics; Näringslära; Obesity; Obesity - genetics; Offspring; original-article; Phosphorylation; Polymorphism; Polymorphism, Genetic - genetics; Promoter Regions, Genetic - genetics; Public Health; RNA, Messenger - genetics; Sterol Esterase - genetics; transmission; Waist-Hip Ratio
• ISSN: 0307-0565; 1476-5497; 1476-5497
• DOI: 10.1038/sj.ijo.0803299

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.