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Nonsynonymous polymorphisms in PLA2G7 gene are associated with the risk of coronary heart disease in a southern Chinese population

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Abstract

Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays an important role in coronary heart disease (CHD). This study was aimed to investigate the associations of polymorphisms (R92H, V279F, I198T, and A379V) in PLA2G7 with CHD. A total of 322 patients with CHD and 414 CHD-free controls were included in the study. Polymorphisms in PLA2G7 were sequenced by DNA Sequencer and statistical analyses were performed to study the associations between polymorphisms and CHD. RH + HH genotype, RH genotype, and H allele of R92H were significantly associated with an increased risk of CHD (P = 0.005, P = 0.009, and P = 0.003, respectively), while no associations were observed between V279F and I198T and CHD (A379V was not analyzed because of deviation from Hardy–Weinberg equilibrium). Correlations between R92H and CHD still existed after adjustment for confounding risk factors of CHD (P = 0.001). Furthermore, stratified analyses showed subgroups of the senior, hypertension, non-smoking, non-diabetics, and male subjects brought a higher risk for CHD (P = 0.015, P = 0.001, P = 0.001, P = 0.002, and P = 0.004, respectively). We also observed a lower level of protective factor HDL-C in CHD patients carrying genotype RH + HH than patients with RR (P = 0.047). Furthermore, we conducted haplotype analysis and detected more harmful effects of haplotypes HVI and RVT as compared with other haplotypes (P = 2.538 × 10−3 and P = 0.031). These findings indicated that R92H variant in PLA2G7 gene might contribute to CHD susceptibility in a southern Chinese population.

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References

  • Cai A, Zheng D, Qiu R, Mai W, Zhou Y (2013) Lipoprotein-associated phospholipase A2 (Lp-PLA(2)): a novel and promising biomarker for cardiovascular risks assessment. Dis Markers 34:323–331

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Casas JP, Ninio E, Panayiotou A, Palmen J, Cooper JA, Ricketts SL, Sofat R, Nicolaides AN, Corsetti JP, Fowkes FG, Tzoulaki I, Kumari M, Brunner EJ, Kivimaki M, Marmot MG, Hoffmann MM, Winkler K, Marz W, Ye S, Stirnadel HA, Boekholdt SM, Khaw KT, Humphries SE, Sandhu MS, Hingorani AD, Talmud PJ (2010) PLA2G7 genotype, lipoprotein-associated phospholipase A2 activity, and coronary heart disease risk in 10,494 cases and 15,624 controls of European Ancestry. Circulation 121:2284–2293

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Charniot JC, Khani-Bittar R, Albertini JP, Giral P, Cherfils C, Cosson C, Guillerm E, Leprince P, Gandjbakhch I, Bonnefont-Rousselot D (2013) Interpretation of lipoprotein-associated phospholipase A2 levels is influenced by cardiac disease, comorbidities, extension of atherosclerosis and treatments. Int J Cardiol 168:132–138

    Article  CAS  PubMed  Google Scholar 

  • Chu AY, Guilianini F, Grallert H, Dupuis J, Ballantyne CM, Barratt BJ, Nyberg F, Chasman DI, Ridker PM (2012) Genome-wide association study evaluating lipoprotein-associated phospholipase A2 mass and activity at baseline and after rosuvastatin therapy. Circulation 5:676–685

    CAS  PubMed  Google Scholar 

  • Corson MA, Jones PH, Davidson MH (2008) Review of the evidence for the clinical utility of lipoprotein-associated phospholipase A2 as a cardiovascular risk marker. Am J Cardiol 101:41F–50F

    Article  CAS  PubMed  Google Scholar 

  • Dada N, Kim NW, Wolfert RL (2002) Lp-PLA2: an emerging biomarker of coronary heart disease. Expert Rev Mol Diagn 2:17–22

    Article  CAS  PubMed  Google Scholar 

  • Daida H, Iwase T, Yagi S, Ando H, Nakajima H (2013) Effect of darapladib on plasma lipoprotein-associated phospholipase A2 activity in Japanese dyslipidemic patients, with exploratory analysis of a PLA2G7 gene polymorphism of Val279Phe. Circ J 77:1518–1525

    Article  CAS  PubMed  Google Scholar 

  • Dohi T, Miyauchi K, Okazaki S, Yokoyama T, Ohkawa R, Nakamura K, Yanagisawa N, Tsuboi S, Ogita M, Yokoyama K, Kurata T, Yatomi Y, Daida H (2011) Decreased circulating lipoprotein-associated phospholipase A2 levels are associated with coronary plaque regression in patients with acute coronary syndrome. Atherosclerosis 219:907–912

    Article  CAS  PubMed  Google Scholar 

  • Elkind MS, Tai W, Coates K, Paik MC, Sacco RL (2006) High-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2, and outcome after ischemic stroke. Arch Intern Med 166:2073–2080

    Article  CAS  PubMed  Google Scholar 

  • Ferreira-Gonzalez I (2014) The epidemiology of coronary heart disease. Rev Esp Cardiol 67:139–144

    Article  PubMed  Google Scholar 

  • Finn AV, Nakano M, Narula J, Kolodgie FD, Virmani R (2010) Concept of vulnerable/unstable plaque. Arterioscler Thromb Vasc Biol 30:1282–1292

    Article  CAS  PubMed  Google Scholar 

  • Garza CA, Montori VM, McConnell JP, Somers VK, Kullo IJ, Lopez-Jimenez F (2007) Association between lipoprotein-associated phospholipase A2 and cardiovascular disease: a systematic review. Mayo Clin Proc 82:159–165

    Article  CAS  PubMed  Google Scholar 

  • Grallert H, Dupuis J, Bis JC, Dehghan A, Barbalic M, Baumert J, Lu C, Smith NL, Uitterlinden AG, Roberts R, Khuseyinova N, Schnabel RB, Rice KM, Rivadeneira F, Hoogeveen RC, Fontes JD, Meisinger C, Keaney JF Jr, Lemaitre R, Aulchenko YS, Vasan RS, Ellis S, Hazen SL, van Duijn CM, Nelson JJ, Marz W, Schunkert H, McPherson RM, Stirnadel-Farrant HA, Psaty BM, Gieger C, Siscovick D, Hofman A, Illig T, Cushman M, Yamamoto JF, Rotter JI, Larson MG, Stewart AF, Boerwinkle E, Witteman JC, Tracy RP, Koenig W, Benjamin EJ, Ballantyne CM (2012) Eight genetic loci associated with variation in lipoprotein-associated phospholipase A2 mass and activity and coronary heart disease: meta-analysis of genome-wide association studies from five community-based studies. Eur Heart J 33:238–251

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Guerra R, Zhao B, Mooser V, Stafforini D, Johnston JM, Cohen JC (1997) Determinants of plasma platelet-activating factor acetylhydrolase: heritability and relationship to plasma lipoproteins. J Lipid Res 38:2281–2288

    CAS  PubMed  Google Scholar 

  • Hou L, Chen S, Yu H, Lu X, Chen J, Wang L, Huang J, Fan Z, Gu D (2009) Associations of PLA2G7 gene polymorphisms with plasma lipoprotein-associated phospholipase A2 activity and coronary heart disease in a Chinese Han population: the Beijing atherosclerosis study. Hum Genet 125:11–20

    Article  CAS  PubMed  Google Scholar 

  • Investigators S, White HD, Held C, Stewart R, Tarka E, Brown R, Davies RY, Budaj A, Harrington RA, Steg PG, Ardissino D, Armstrong PW, Avezum A, Aylward PE, Bryce A, Chen H, Chen MF, Corbalan R, Dalby AJ, Danchin N, De Winter RJ, Denchev S, Diaz R, Elisaf M, Flather MD, Goudev AR, Granger CB, Grinfeld L, Hochman JS, Husted S, Kim HS, Koenig W, Linhart A, Lonn E, Lopez-Sendon J, Manolis AJ, Mohler ER 3rd, Nicolau JC, Pais P, Parkhomenko A, Pedersen TR, Pella D, Ramos-Corrales MA, Ruda M, Sereg M, Siddique S, Sinnaeve P, Smith P, Sritara P, Swart HP, Sy RG, Teramoto T, Tse HF, Watson D, Weaver WD, Weiss R, Viigimaa M, Vinereanu D, Zhu J, Cannon CP, Wallentin L (2014) Darapladib for preventing ischemic events in stable coronary heart disease. N Engl J Med 370:1702–1711

    Article  Google Scholar 

  • Jabor B, Choi H, Ruel I, Hafiane A, Mourad W, Genest J (2013) Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) in acute coronary syndrome: relationship with low-density lipoprotein cholesterol. Can J Cardiol 29:1679–1686

    Article  PubMed  Google Scholar 

  • Jang Y, Waterworth D, Lee JE, Song K, Kim S, Kim HS, Park KW, Cho HJ, Oh IY, Park JE, Lee BS, Ku HJ, Shin DJ, Lee JH, Jee SH, Han BG, Jang HY, Cho EY, Vallance P, Whittaker J, Cardon L, Mooser V (2011) Carriage of the V279F null allele within the gene encoding Lp-PLA(2) is protective from coronary artery disease in South Korean males. PLoS One 6:e18208

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Johnson JL, Shi Y, Snipes R, Janmohamed S, Rolfe TE, Davis B, Postle A, Macphee CH (2014) Effect of darapladib treatment on endarterectomy carotid plaque lipoprotein-associated phospholipase A2 activity: a randomized, controlled trial. PLoS One 9:e89034

    Article  PubMed Central  PubMed  Google Scholar 

  • Kruse S, Mao XQ, Heinzmann A, Blattmann S, Roberts MH, Braun S, Gao PS, Forster J, Kuehr J, Hopkin JM, Shirakawa T, Deichmann KA (2000) The Ile198Thr and Ala379 Val variants of plasmatic PAF-acetylhydrolase impair catalytical activities and are associated with atopy and asthma. Am J Hum Genet 66:1522–1530

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Li L, Qi L, Lv N, Gao Q, Cheng Y, Wei Y, Ye J, Yan X, Dang A (2011) Association between lipoprotein-associated phospholipase A2 gene polymorphism and coronary artery disease in the Chinese Han population. Ann Hum Genet 75:605–611

    Article  CAS  PubMed  Google Scholar 

  • Liu PY, Li YH, Wu HL, Chao TH, Tsai LM, Lin LJ, Shi GY, Chen JH (2006) Platelet-activating factor-acetylhydrolase A379V (exon 11) gene polymorphism is an independent and functional risk factor for premature myocardial infarction. J Thromb Haemost 4:1023–1028

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Wang W, Qi Y, Yong Q, Zhou G, Wang M, Sun J, Liu J, Jia Z, Zhao D (2014a) Association between the lipoprotein-associated phospholipase A2 activity and the progression of subclinical atherosclerosis. J Atheroscler Thromb 21:532–542

    CAS  PubMed  Google Scholar 

  • Liu X, Zhu RX, Tian YL, Li Q, Li L, Deng SM, He ZY (2014b) Association of PLA2G7 gene polymorphisms with ischemic stroke in northern Chinese Han population. Clin Biochem 47:404–408

    Article  CAS  PubMed  Google Scholar 

  • Lloyd-Jones DM, Larson MG, Beiser A, Levy D (1999) Lifetime risk of developing coronary heart disease. Lancet 353:89–92

    Article  CAS  PubMed  Google Scholar 

  • Maiolino G, Lenzini L, Pedon L, Cesari M, Seccia TM, Frigo AC, Rossitto G, Caroccia B, Rossi GP (2015) Lipoprotein-associated phospholipase A2 single-nucleotide polymorphisms and cardiovascular events in patients with coronary artery disease. J Cardiovasc Med 16:29–36

    Article  CAS  Google Scholar 

  • National Cholesterol Education Program Expert Panel on Detection E, Treatment of High Blood Cholesterol in A (2002) 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) final report. Circulation 106:3143–3421

    Google Scholar 

  • Nichols M, Townsend N, Scarborough P, Rayner M (2013) European cardiovascular disease statistics 4th edition 2012: EuroHeart II. Eur Heart J 34:3007

    Article  Google Scholar 

  • Ninio E, Tregouet D, Carrier JL, Stengel D, Bickel C, Perret C, Rupprecht HJ, Cambien F, Blankenberg S, Tiret L (2004) Platelet-activating factor-acetylhydrolase and PAF-receptor gene haplotypes in relation to future cardiovascular event in patients with coronary artery disease. Hum Mol Genet 13:1341–1351

    Article  CAS  PubMed  Google Scholar 

  • Serruys PW, Garcia-Garcia HM, Buszman P, Erne P, Verheye S, Aschermann M, Duckers H, Bleie O, Dudek D, Botker HE, von Birgelen C, D’Amico D, Hutchinson T, Zambanini A, Mastik F, van Es GA, van der Steen AF, Vince DG, Ganz P, Hamm CW, Wijns W, Zalewski A, Integrated B, Imaging Study I (2008) Effects of the direct lipoprotein-associated phospholipase A(2) inhibitor darapladib on human coronary atherosclerotic plaque. Circulation 118:1172–1182

    Article  CAS  PubMed  Google Scholar 

  • Shimokata K, Yamada Y, Kondo T, Ichihara S, Izawa H, Nagata K, Murohara T, Ohno M, Yokota M (2004) Association of gene polymorphisms with coronary artery disease in individuals with or without nonfamilial hypercholesterolemia. Atherosclerosis 172:167–173

    Article  CAS  PubMed  Google Scholar 

  • Suchindran S, Rivedal D, Guyton JR, Milledge T, Gao X, Benjamin A, Rowell J, Ginsburg GS, McCarthy JJ (2010) Genome-wide association study of Lp-PLA(2) activity and mass in the Framingham Heart Study. PLoS Genet 6:e1000928

    Article  PubMed Central  PubMed  Google Scholar 

  • Sutton BS, Crosslin DR, Shah SH, Nelson SC, Bassil A, Hale AB, Haynes C, Goldschmidt-Clermont PJ, Vance JM, Seo D, Kraus WE, Gregory SG, Hauser ER (2008) Comprehensive genetic analysis of the platelet activating factor acetylhydrolase (PLA2G7) gene and cardiovascular disease in case-control and family datasets. Hum Mol Genet 17:1318–1328

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tselepis AD, Karabina SA, Stengel D, Piedagnel R, Chapman MJ, Ninio E (2001) N-linked glycosylation of macrophage-derived PAF-AH is a major determinant of enzyme association with plasma HDL. J Lipid Res 42:1645–1654

    CAS  PubMed  Google Scholar 

  • Wang Q, Hao Y, Mo X, Wang L, Lu X, Huang J, Cao J, Li H, Gu D (2010) PLA2G7 gene polymorphisms and coronary heart disease risk: a meta-analysis. Thromb Res 126:498–503

    Article  CAS  PubMed  Google Scholar 

  • Wang WY, Zhang J, Wu WY, Li J, Ma YL, Chen WH, Yan H, Wang K, Xu WW, Shen JH, Wang YP (2011) Inhibition of lipoprotein-associated phospholipase A2 ameliorates inflammation and decreases atherosclerotic plaque formation in ApoE-deficient mice. PLoS One 6:e23425

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wilensky RL, Shi Y, Mohler ER 3rd, Hamamdzic D, Burgert ME, Li J, Postle A, Fenning RS, Bollinger JG, Hoffman BE, Pelchovitz DJ, Yang J, Mirabile RC, Webb CL, Zhang L, Zhang P, Gelb MH, Walker MC, Zalewski A, Macphee CH (2008) Inhibition of lipoprotein-associated phospholipase A2 reduces complex coronary atherosclerotic plaque development. Nat Med 14:1059–1066

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Winkler K, Hoffmann MM, Winkelmann BR, Friedrich I, Schafer G, Seelhorst U, Wellnitz B, Wieland H, Boehm BO, Marz W (2007) Lipoprotein-associated phospholipase A2 predicts 5-year cardiac mortality independently of established risk factors and adds prognostic information in patients with low and medium high-sensitivity C-reactive protein (the Ludwigshafen risk and cardiovascular health study). Clin Chem 53:1440–1447

    Article  CAS  PubMed  Google Scholar 

  • Xu L, Zhou J, Huang S, Huang Y, Le Y, Jiang D, Wang F, Yang X, Xu W, Huang X, Dong C, Zhang L, Ye M, Lian J, Duan S (2013) An association study between genetic polymorphisms related to lipoprotein-associated phospholipase A(2) and coronary heart disease. Exp Ther Med 5:742–750

    PubMed Central  PubMed  Google Scholar 

  • Zheng GH, Chen HY, Xiong SQ, Chu JF (2011) Lipoprotein-associated phospholipase A2 gene V279F polymorphisms and coronary heart disease: a meta-analysis. Mol Biol Rep 38:4089–4099

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by Nature Science Foundation of Jiangsu Province, China (BK 2009450) and Social Development Foundation of Jiangsu, China (BE 2011804).

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Correspondence to Xiang Lu.

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Hong, M., Zhang, M. & Lu, X. Nonsynonymous polymorphisms in PLA2G7 gene are associated with the risk of coronary heart disease in a southern Chinese population. Mamm Genome 26, 191–199 (2015). https://doi.org/10.1007/s00335-015-9559-x

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  • DOI: https://doi.org/10.1007/s00335-015-9559-x

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