Abstract
Endothelial lipase (LIPG) is a member of the triglyceride lipase family which includes hepatic lipase and lipoprotein lipase. Its activity is related to clinically important parameters like blood lipid levels, hypertension, and obesity. In this work, we investigated the association of a LIPG promoter polymorphism, rs9958947C>T, with susceptibility to ischemic stroke in a Korean population. A total of 1,144 subjects (656 cerebral infarction patients and 488 controls) were enrolled on a voluntary basis. The rs9958947C>T polymorphism was genotyped using the single-base extension method. The association of rs9958947C>T with disease status was evaluated by statistical analyses. The frequencies of the rs9958947 C and T alleles were significantly different between the stroke patient group and control group (OR [95% CI], 1.300 [1.000–1.691], P=0.0449). A significantly higher frequency of the CT+TT genotype was observed in the patient group compared to the control group (CC/CT+TT, OR [95% CI], 1.632 [1.094–2.435], P=0.0164). The results suggest that the T allele of the LIPG promoter polymorphism rs9958947C>T should be considered as a genetic risk factor for ischemic stroke. Further association studies in other ethnic populations would help to generalize this hypothesis.
Similar content being viewed by others
References
Aulchenko YS, Ripatti S, Lindqvist I, Boomsma D, Heid IM, Pramstaller PP, et al. (2009) Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. Nat. Genet. 41: 47–55.
Edmondson AC, Brown RJ, Kathiresan S, Cupples LA, Demissie S, Manning AK, et al. (2009) Loss-of-function variants in endothelial lipase are a cause of elevated HDL cholesterol in humans. J. Clin. Invest. 119: 1042–1050.
Gretarsdottir S, Thorleifsson G, Reynisdottir ST, Manolescu A, Jonsdottir S, Jonsdottir T, et al. (2003) The gene encoding phosphodiesterase 4D confers risk of ischemic stroke. Nat. Genet. 35: 131–138.
Heid IM, Boes E, Müller M, Kollerits B, Lamina C, Coassin S, et al. (2008) Genome-wide association analysis of high-density lipoprotein cholesterol in the population-based KORA study sheds new light on intergenic regions. Circ. Cardiovasc. Genet. 1: 10–20.
Helgadottir A, Manolescu A, Thorleifsson G, Gretarsdottir S, Jonsdottir H, Thorsteinsdottir U, et al. (2004) The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke. Nat. Genet. 36: 233–239.
Ishida T, Choi S, Kundu RK, Hirata K, Rubin EM, Cooper AD, et al. (2003) Endothelial lipase is a major determinant of HDL level. J. Clin. Invest. 111: 347–355.
Ishida T, Choi SY, Kundu RK, Spin J, Yamashita T, Hirata K, et al. (2004) Endothelial lipase modulates susceptibility to atherosclerosis in apolipoprotein-E-deficient mice. J. Biol. Chem. 279: 45085–4509
Jaye M, Lynch KJ, Krawiec J, Marchadier D, Maugeais C, Doan K, et al. (1999) A novel endothelial-derived lipase that modulates HDL metabolism. Nat. Genet. 21: 424–428.
Jensen MK, Rimm EB, Mukamal KJ, Edmondson AC, Rader DJ, Vogel U, et al. (2009) The T111I variant in the endothelial lipase gene and risk of coronary heart disease in three independent populations. Eur. Heart J. 30: 1584–1589.
Kathiresan S, Melander O, Guiducci C, Surti A, Burtt NP, Rieder MJ, et al. (2008) Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat. Genet. 40: 189–197.
Kathiresan S, Willer CJ, Peloso GM, Demissie S, Musunuru K, Schadt EE, et al. (2009) Common variants at 30 loci contribute to polygenic dyslipidemia. Nat. Genet. 41: 56–65.
Kim NS, Ko MM, Cha MH, Oh SM and Bang OS (2010) Age and sex dependent genetic effects of neuropeptide Y promoter polymorphism on susceptibility to ischemic stroke in Koreans. Clin. Chim. Acta 411: 1243–1247.
Kim NS, Oh SM, Ko MM, Cha MH, Kang BK and Bang OS (2009) Association of the C-399T promoter polymorphism of neuropeptide Y with susceptibility to ischemic stroke. Clin. Biochem. 42: 1699–1704.
Krug T, Manso H, Gouveia L, Sobral J, Xavier JM, Albergaria I, et al. (2010) Kalirin: a novel genetic risk factor for ischemic stroke. Hum. Genet. 127: 513–523.
Kubo M, Hata J, Ninomiya T, Matsuda K, Yonemoto K, Nakano T, et al. (2007) A nonsynonymous SNP in PRKCH (protein kinase C eta) increases the risk of cerebral infarction. Nat. Genet. 39: 212–217.
Lee C and Kong M (2007) An interactive association of common sequence variants in the neuropeptide Y gene with susceptibility to ischemic stroke. Stroke 38: 2663–2669.
Linsel-Nitschke P and Tall AR (2005) HDL as a target in the treatment of atherosclerotic cardiovascular disease. Nat. Rev. Drug Discov. 4: 193–205.
Ma L, Yang J, Runesha HB, Tanaka T, Ferrucci L, Bandinelli S, et al. (2010) Genome-wide association analysis of total cholesterol and high-density lipoprotein cholesterol levels using the Framingham heart study data. BMC Med. Genet. 11: 55.
Mank-Seymour AR, Durham KL, Thompson JF, Seymour AB and Milos PM (2004) Association between single-nucleotide polymorphisms in the endothelial lipase (LIPG) gene and high-density lipoprotein cholesterol levels. Biochim. Biophys. Acta 1636:40–46.
Maugeais C, Tietge UJ, Broedl UC, Marchadier D, Cain W, McCoy MG, et al. (2003) Dose-dependent acceleration of high-density lipoprotein catabolism by endothelial lipase. Circulation 108: 2121–2126.
Otokozawa S, Ai M, Asztalos BF, White CC, Demissie-Banjaw S, Cupples LA, et al. (2010) Direct assessment of plasma low density lipoprotein and high density lipoprotein cholesterol levels and coronary heart disease: Results from the Framingham Offspring Study. Atherosclerosis 213: 251–255.
Santamar’ia A, Mateo J, Tirado I, Oliver A, Belv’is R, Mart’i-F’abregas J, et al. (2004) Homozygosity of the T allele of the 46 C→T polymorphism in the F12 gene is a risk factor for ischemic stroke in the Spanish population. Stroke 35: 1795–1799.
Shimokawa Y, Hirata K, Ishida T, Kojima Y, Inoue N, Quertermous T, et al. (2005) Increased expression of endothelial lipase in rat models of hypertension. Cardiovasc. Res. 66: 594–600.
Strang AC, Hovingh GK, Stroes ES and Kastelein JJ (2009) The genetics of high-density lipoprotein metabolism: clinical relevance for therapeutic approaches. Am. J. Cardiol. 104: 22E–31E.
Vergeer M, Cohn DM, Boekholdt SM, Sandhu MS, Prins HM, Ricketts SL, et al. (2010) Lack of association between common genetic variation in endothelial lipase (LIPG) and the risk for CAD and DVT. Atherosclerosis 211: 558–564.
Willer CJ, Sanna S, Jackson AU, Scuteri A, Bonnycastle LL, Clarke R, et al. (2008) Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat. Genet. 40: 161–169.
Wu X, Huang H, Tang F, Le K, Xu S and Liu P (2010) Regulated expression of endothelial lipase in atherosclerosis. Mol. Cell. Endocrinol. 315: 233–238.
Yamaguchi S, Yamada Y, Metoki N, Yoshida H, Satoh K, Ichihara S, et al. (2006) Genetic risk for atherothrombotic cerebral infarction in individuals stratified by sex or conventional risk factors for atherosclerosis. Int. J. Mol. Med. 18: 871–883.
Yu JT, Yu NN, Gao SS, Song JH, Ma T, Wang ND, et al. (2010) Neuropeptide Y polymorphisms and ischemic stroke in Chinese population. Clin. Chim. Acta 411: 242–245.
Zeljkovic A, Vekic J, Spasojevic-Kalimanovska V, Jelic-Ivanovic Z, Bogavac-Stanojevic N, Gulan B, et al. (2010) LDL and HDL subclasses in acute ischemic stroke: prediction of risk and short-term mortality. Atherosclerosis 210: 548–554.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kim, N.S., Ko, M.M., Cha, M.H. et al. LIPG promoter polymorphism is associated with ischemic stroke in Korean population. Genes Genom 34, 165–171 (2012). https://doi.org/10.1007/s13258-011-0197-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13258-011-0197-8