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, Philippa J., Palmen, Jutta, Luan, Jian'an, Flavell, Dave, Byrne, Christopher D., Waterworth, Dawn M. and Wareham, Nicholas J. (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. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1537 (3), 239-244. (doi:10.1016/S0925-4439(01)00076-X).

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 ?-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.

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Contributors

Author: Christopher D. Byrne

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