title: Variation in the promoter of the human hormone sensitive lipase gene shows gender specific effects on insulin and lipid levels: results from the Ely study.
abstract: We previously identified a hormone sensitive lipase (HSL) promoter variant, -60C>G, which in vitro exhibits 40% reduced promoter activity. In this study we examined the effect of the -60C>G on glycemic and lipid measures in the population based Ely study of metabolic function and insulin resistance in 218 middle-aged men and 276 middle-aged women. Adipose tissue HSL is the rate-limiting step in triglyceride lipolysis, generating free fatty acids for energy utilization. HSL is also expressed in pancreatic beta-cells where its activity therefore may affect insulin secretion. In the women, carriers of the HSL -60G allele had significantly lower fasting insulin levels (P=0.0005) and a lower total area under the curve for insulin during the oral glucose tolerance test (P=0.005). There was no demonstrable association in men with these measures of insulin sensitivity but carriers of the -60G allele had significantly lower fasting non-esterified fatty acid (NEFA) levels (P=0.025) and higher low density lipoprotein cholesterol levels (P=0.02) than men who were non-carriers. This study provides additional evidence for a role for HSL in the development of insulin resistance, from which carriers of the -60G allele, associated here with markers of insulin sensitivity in women, and with lower NEFA levels in men, might be protected.
authors.affiliation: Division of Cardiovascular Genetics, Department of Medicine, Royal Free and University College Medical School, The Rayne Institute, London, UK. p.talmud@ucl.ac.uk
authors.forename: P J
authors.initials: PJ
authors.lastname: Talmud
authors.forename: J
authors.initials: J
authors.lastname: Palmen
authors.forename: J
authors.initials: J
authors.lastname: Luan
authors.forename: D
authors.initials: D
authors.lastname: Flavell
authors.forename: C D
authors.initials: CD
authors.lastname: Byrne
authors.forename: D M
authors.initials: DM
authors.lastname: Waterworth
authors.forename: N J
authors.initials: NJ
authors.lastname: Wareham
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D005260:Female; D014644:Genetic Variation; D005951:Glucose Tolerance Test; D006579:Heterozygote; D006801:Humans; D007328:Insulin / Q000097:blood* / Q000493:pharmacokinetics; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D012737:Sex Factors; D002787:Sterol Esterase / Q000097:blood / Q000235:genetics*
chemical_list: D007328:Insulin; D008055:Lipids; D002787:Sterol Esterase