Investigation into the role of the hormone sensitive lipase -60C>G promoter variant in morbid obesity.
BACKGROUND
Hormone sensitive lipase (HSL) plays a central role in free fatty acid homeostasis in adipose tissue and in pancreatic beta-cells, where it contributes to the control of insulin secretion by generating long-chain fatty acids.


OBJECTIVE
We examined the frequency and association of the functional HSL promoter variant, -60C>G, in a German cohort of morbidly obese women (N=239) and men (N=55) and compared the frequency to a cohort of 199 blood donors, recruited from the same region.


RESULTS
The rare allele frequency of -60C>G, in the obese individuals was significantly lower 0.031 (95% CI 0.02, 0.04), than that in the blood donors 0.061 (95% CI 0.04, 0.08) p=0.05. The association of the HSL -60C>G with lipid and glucose parameters was examined in the obese women (there were too few men for comparative analysis). In the obese women, those heterozygous for the -60G had significantly higher glucose levels compared to CC women, 142.71 (+/-16.23) mg/dl vs. 110.34 (+/-1.79) mg/dl, respectively (p=0.0001). There was no statistically significant difference in other parameters.


CONCLUSIONS
This study confirms a role for HSL in glucose homeostasis and the reduced frequency of the low expressing -60G promoter variant in obese individuals, together with existing published data, suggests that this allele might be protective against obesity.
Talmud
Philippa J
PJ
Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Department of Medicine, The Rayne Institute, Royal Free and University College Medical School, London WC1E 6JF, UK. p.talmud@ucl.ac.uk
Palmen
Jutta
J
Wolf
Anna M
AM
Beisiegel
Ulrike
U
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D007328:Insulin / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008049:Lipase / Q000097:blood* / Q000235:genetics*; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*
D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D008049:Lipase