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

Emma A Nilsson, L Johansson, Kristoffer Ström, J Hoffstedt, Leif Groop, Cecilia Holm, Martin Ridderstråle

Research output: Contribution to journalArticlepeer-review

13 Citations (SciVal)

Abstract

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.
Original languageEnglish
Pages (from-to)1442-1448
JournalInternational Journal of Obesity
Volume30
Issue number9
DOIs
Publication statusPublished - 2006

Bibliographical note

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Department of Experimental Medical Science (013210000), Pediatrics/Urology/Gynecology/Endocrinology (013240400), Endocrinology (013241500), Molecular Endocrinology (013212018), Epigenetics and Diabetes (013241505), Diabetes and Endocrinology (013241530), Clinical Obesity (013241521)

Subject classification (UKÄ)

  • Nutrition and Dietetics

Keywords

  • transmission
  • case-control association study
  • hormone-sensitive lipase
  • disequilibrium test
  • adipose tissue

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