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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

Talmud, PJ; Palmen, J; Luan, JN; Flavell, D; Byrne, CD; Waterworth, DM; Wareham, NJ; (2001) 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. BBA-MOL BASIS DIS , 1537 (3) 239 - 244.

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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. (C) 2001 Elsevier Science B.V. All rights reserved.

Type:Article
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
Keywords:hormone sensitive lipase, insulin resistance, fasting insulin levels, genetic polymorphism, FATTY-ACIDS, DIABETES-MELLITUS, ADIPOSE-TISSUE, GLUCOSE, RESISTANCE, SECRETION, LIPOLYSIS, OBESITY, IDENTIFICATION, MECHANISMS
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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