Hepatic lipase, genetically elevated high-density lipoprotein, and risk of ischemic cardiovascular disease.
BACKGROUND
Hepatic lipase influences metabolism of high-density lipoprotein (HDL), a risk factor for ischemic cardiovascular disease (ICD: ischemic heart disease and ischemic cerebrovascular disease).


OBJECTIVE
We tested the hypothesis that genetic variation in the hepatic lipase genetic variants V73M, N193S, S267F, L334F, T383M, and -480c>t influence levels of lipids, lipoproteins, and apolipoproteins and risk of ICD.


METHODS
For the cross-sectional study, we genotyped 9003 individuals from the Copenhagen City Heart Study; hereof were 8971 individuals included in the prospective study, 1747 of whom had incident ICD during 28 yr of follow-up. For the case-control studies, 2110 ischemic heart disease patients vs. 4899 controls and 769 ischemic cerebrovascular disease patients vs. 2836 controls, respectively, were genotyped. Follow-up was 100% complete.


RESULTS
HDL cholesterol was higher by 0.21 mmol/liter in S267F heterozygotes, by 0.06 mmol/liter in -480c>t heterozygotes, and by 0.13 mmol/liter in -480c>t homozygotes, as compared with noncarriers. These HDL increases theoretically predicted hazard ratios for ICD of 0.87 [95% confidence interval (CI) 0.84-0.90], 0.96 (95% CI 0.95-0.97), and 0.91 (95% CI 0.89-0.94), respectively; this calculation assumes that genetically elevated HDL levels confer decreased risk similar to common HDL elevations. In contrast, when all cases and controls were combined, the observed odds ratios for ICD for these three genetic variants vs. noncarriers were 1.19 (0.76-1.88), 1.04 (0.96-1.13), and 1.08 (0.89-1.30), respectively. Hazard/odds ratios for ICD in carriers vs. noncarriers of the four remaining hepatic lipase genetic variants did not differ consistently from 1.0.


CONCLUSIONS
Hepatic lipase genetic variants with elevated levels of HDL cholesterol did not associate with risk of ICD.
Johannsen
Trine Holm
TH
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
Kamstrup
Pia R
PR
Andersen
Rolf V
RV
Jensen
Gorm B
GB
Sillesen
Henrik
H
Tybjaerg-Hansen
Anne
A
Nordestgaard
Børge G
BG
D000328:Adult; D019943:Amino Acid Substitution; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000235:genetics; D002543:Cerebral Hemorrhage / Q000453:epidemiology / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006580:Genetic Carrier Screening; D014644:Genetic Variation; D006801:Humans; D008049:Lipase / Q000097:blood* / Q000235:genetics*; D008075:Lipoproteins, HDL / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics; D017202:Myocardial Ischemia / Q000097:blood* / Q000235:genetics*; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000235:genetics
D008076:Cholesterol, HDL; C504173:LIPC protein, human; D008075:Lipoproteins, HDL; D008049:Lipase