Background: Left main (LM) disease is rare but the most hazardous phenotype of coronary artery disease (CAD). Thus, early detection of participants at high risk of developing left main coronary heart disease (LM-CAD) is crucial. The aim of this study was to identify gene polymorphisms which could distinguish participants who are at high risk of developing LM-CAD. Such a candidate can be the prostaglandin I2 or prostacyclin (PGI2) gene. Methods: The DNA of 254 participants (151 participants with angiographically documented LM-CAD and 103 healthy controls) was analyzed for the frequency of C1117A polymorphism in the gene coding CYP8A1. Results: The genotype distribution was different between the LM-CAD and the control group. Particularly, the CC genotype of CYP8A1 was commoner in the LM-CAD than in the healthy group (P < .001). Allele frequencies were also differently distributed between the 2 groups. C allele frequency was higher in LM-CAD group (P = .016). Conclusions: The CC genotype of C1117A polymorphism is associated with higher risk of LM-CAD, which prospectively may have potential importance in screening high-risk populations. However, further investigations in larger populations are required to confirm these findings.
KitsiosGDDahabrehIJTrikalinosTASchmidCHHugginsGSKentDM. Heterogenity of the phenotypic definition of coronary artery disease and its impact on genetic association studies. Circ Cardiovasc Genet. 2011;4(1):58–67.
2.
FischerMMayerBBaesslerA. Familial aggregation of left main coronary artery disease and future risk of coronary events in asymptomatic siblings of affected patients. Eur Heart J. 2007;28(20):2432–2437.
3.
SheaSOttmanRGabrieliCSteinZNicholsA. Family history as an independent risk factor for coronary artery disease. J Am Coll Cardiol. 1984;4(4):793–801.
4.
UenoYKoikeHAnnohSNishioS. Anti-inflammator effects of beraprost sodium, a stable analogue of PGI2, and its mechanisms. Prostaglandins. 1997;53(4):279–89.
5.
ZhouWHashimotoKGoleniewskaK. Prostaglandin I2 analogs inhibit proinflammatory cytokine production and tcell stimulatory function of dendritic cells. J Immunol. 2007;178(2):702–710.
6.
HashimotoKGrahamBSGeraciMW. Signaling through the prostaglandin I2 receptor IP protects against respiratory syncytial virus-induced illness. J Virol. 2004;78(19):10303–10309.
7.
BoieYRushmoreTHDarmon-GoodwinA. Cloning and expression of a cDNA for the human prostanoid IP receptor. J Biol Chem. 1994;269(16):12173–12178.
8.
NakagawaOTanakaIUsuiT. Molecular cloning of human prostacyclin receptor cDNA and its gene expression in the cardiovascular system. Circulation. 1994;90(4):1643–1647.
9.
LuttmannWHerzogVVirchowJCJrMatthysHThierauchKHKroegelC. Prostacyclin modulates granulocyte/macrophage colony-stimulating factor release by human blood mononuclear cells. Pulm Pharmacol. 1996;9(1):43–48.
10.
YokoyamaCYabukiTInoueH. Human gene encoding prostacyclin synthase (PTGIS): genomic organization, chromosomal localization and promoter activity. Genomics. 1996;36(2):296–304.
11.
IwaiNKatsuyaTIshikawaK. Human prostacyclin synthase gene and hypertension: the Suita Study. Circulation. 1999;100(22):2231–2236.
12.
NakayamaTSomaMRehemudulaD. Association of 5’upstream promoter region of prostacyclin synthase gene variant with cerebral infarction. Am J Hypertens. 2000;13(12):1263–1267.
13.
NakayamaTSomaMSaitoS. Association of a novel single nucleotide polymorphism of the prostacyclin synthase gene with myocardial infarction. Am Heart J. 2002;143(5):797–801.
14.
KolovouGVasiliadisIKolovouV. The role of common variants of the cholesteryl ester transfer protein gene in left main coronary artery disease. Lipids Health Dis. 2011;10:156.
15.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486–2497.
16.
FaulFErdfelderELangAGBuchnerA. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39(2):175–191.
17.
GiannoglouGDAntoniadisAPChatzizisisYSDamvopoulouEParcharidisGELouridasGE. Prevalence of narrowing ≥50% of the left main coronary artery among 17,300 patients having coronary angiography. Am J Cardiol. 2006;98(9):120.
18.
SoleimaniAAbbasiAKazzaziEH. Prevalence of left main coronary artery disease among patients with ischemic heart disease: insights from the Tehran angiography registry. Minerva Cardioangiol. 2009;57(2):175–183.
19.
CohenMVGorlioR. Main left coronary artery disease. Circulation. 1975;52(2):275.
20.
CrittinJWaiersDDTherouxPMizgalaHF. Left main coronary artery stenosis in young patients. Chest. 1979;76(5):608.
21.
VelicanCVelicanD. Natural resistance to atherosclerosis exhibited by the first centimeter of left and right coronary arteries. Atherosclerosis. 1984;50(2):173–181.
22.
HirakowR. Development of the cardiac blood vessels in staged human embryos. Acta Anat (Basel). 1983;115(3):220–230.
23.
RongishBJTorryRJTuckerDCTomanekRJ. Neovascularization of embryonic rat hearts cultured in oculo closely mimics in utero coronary vessel development. J Vasc Res. 1994;31(4):205–215.
24.
RatajskaAFiejkaE. Prenatal development of coronary arteries in the rat: morphologic patterns. Anat Embryol (Berl). 1999;200(5):533–540.
25.
BogersAJGittenberger-de GrootACPoelmannREPéaultBMHuysmansHA. Development of the origin of the coronary arteries, a matter of ingrowth or outgrowth?Anat Embryol (Berl). 1989;180(5):437–441.
26.
WaldoKLWillnerWKirbyML. Origin of the proximal coronary artery stems and a review of ventricular vascularization in the chick embryo. Am J Anat. 1990;188(2):109–120.
27.
FischerMBroeckelUHolmerS. Distinct heritable patterns of angiographic coronary artery disease in families with myocardial infarction. Circulation. 2005;111(7):855–862.
28.
FriedmanMHHutchinsGMBargeronCBDetersOJMarkFF. Correlation between intimal thickness and fluid shear in human arteries. Atherosclerosis. 1981;39(3):425.
29.
KawabeJUshikubiFHasebeN. Prostacyclin in vascular diseases-recent insights and future perspectives. Circ J. 2010;74(5):836–843.
30.
XiangXieMaYTFuZY. Haplotype analysis of the CYP8A1 gene associated with myocardial infarction. Clin Appl Thromb Hemost. 2009;15(5):574–580.
31.
El-MenyarAAAl SuwaidiJHolmesDRJr. Left main coronary artery stenosis: state-of-the-art. Curr Probl Cardiol. 2007;32(3):103–193.
32.
KolovouGDAnagnostopoulouKKMikhailidisDP. Association of apolipoprotein E genotype with early onset of coronary heart disease in Greek men. Angiology. 2005;56(6):663–670.
