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

Nilsson, Emma A LU orcid ; Johansson, L ; Ström, Kristoffer LU ; Hoffstedt, J ; Groop, Leif LU ; Holm, Cecilia LU and Ridderstråle, Martin LU (2006) In International Journal of Obesity 30(9). p.1442-1448
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... (More)
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. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
transmission, case-control association study, hormone-sensitive lipase, disequilibrium test, adipose tissue
in
International Journal of Obesity
volume
30
issue
9
pages
1442 - 1448
publisher
Nature Publishing Group
external identifiers
  • wos:000240063200017
  • scopus:33748112924
ISSN
1476-5497
DOI
10.1038/sj.ijo.0803299
language
English
LU publication?
yes
additional info
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)
id
b979245d-e4cc-4c0d-9e81-a0c1b691fb47 (old id 154647)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16534522&dopt=Abstract
date added to LUP
2016-04-01 12:31:00
date last changed
2024-01-08 23:10:13
@article{b979245d-e4cc-4c0d-9e81-a0c1b691fb47,
  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.}},
  author       = {{Nilsson, Emma A and Johansson, L and Ström, Kristoffer and Hoffstedt, J and Groop, Leif and Holm, Cecilia and Ridderstråle, Martin}},
  issn         = {{1476-5497}},
  keywords     = {{transmission; case-control association study; hormone-sensitive lipase; disequilibrium test; adipose tissue}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{1442--1448}},
  publisher    = {{Nature Publishing Group}},
  series       = {{International Journal of Obesity}},
  title        = {{The hormone-sensitive lipase C-60G promoter polymorphism is associated with increased waist circumference in normal-weight subjects.}},
  url          = {{http://dx.doi.org/10.1038/sj.ijo.0803299}},
  doi          = {{10.1038/sj.ijo.0803299}},
  volume       = {{30}},
  year         = {{2006}},
}