Lack of association between common genetic variation in endothelial lipase (LIPG) and the risk for CAD and DVT.
OBJECTIVE
Low levels of high-density lipoprotein cholesterol (HDL-C) are a risk factor for coronary artery disease (CAD) and possibly for deep venous thrombosis (DVT). Endothelial lipase is involved in HDL-C metabolism. Common variants in the endothelial lipase gene (LIPG) have been reported to be associated with HDL-C levels and atherothrombosis, but these findings were not consistent. We determined whether five tagging single nucleotide polymorphisms (SNP) in LIPG were associated with lipid parameters, the risk of CAD and the risk of DVT.


METHODS
We used the prospective case-control study nested in the EPIC-Norfolk cohort (1138 CAD cases, 2237 matched controls) for the initial association study and, subsequently, the ACT study (185 patients with documented DVT, 586 patients in which DVT was ruled out) to replicate our findings regarding DVT risk.


RESULTS
In EPIC-Norfolk, we found that the minor allele of one SNP, rs2000813 (p.T111I), was associated with moderately higher HDL-C and apolipoprotein A-I levels, higher HDL particle number and larger HDL size. No variants were associated with CAD risk, but three variants were associated with DVT risk (odds ratios 0.60 [95%CI 0.43-0.84], 2.04 [95%CI 1.40-2.98] and 1.67 [95%CI 1.18-2.38] per minor allele for rs2000813, rs6507931 and rs2097055 respectively, p<0.005 for each). However, the association between LIPG SNPs and DVT risk could not be replicated in the ACT study.


CONCLUSIONS
Our data support a modest association between the LIPG rs2000813 variant and parameters of HDL metabolism, but no association between common genetic variants in LIPG and CAD or DVT risk.
Vergeer
Menno
M
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. m.vergeer@amc.uva.nl
Cohn
Danny M
DM
Boekholdt
S Matthijs
SM
Sandhu
Manjinder S
MS
Prins
Hester M
HM
Ricketts
Sally L
SL
Wareham
Nicholas J
NJ
Kastelein
John J P
JJ
Khaw
Kay-Tee
KT
Kamphuisen
Pieter W
PW
Dallinga-Thie
Geesje M
GM
D000368:Aged; D000483:Alleles; D008076:Cholesterol, HDL / Q000378:metabolism; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D013927:Thrombosis / Q000235:genetics; D020246:Venous Thrombosis / Q000235:genetics*
D008076:Cholesterol, HDL; C410382:LIPG protein, human; D008049:Lipase