{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T05:24:44Z","timestamp":1774329884269,"version":"3.50.1"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lipoprotein-associated phospholipase A2 (Lp-PLA<jats:sub>2<\/jats:sub>) levels are associated with the development of atherosclerosis. We aimed to assess the genetic determinants of Lp-PLA<jats:sub>2<\/jats:sub> activity and mass by genotyping multiple polymorphisms in <jats:italic>PLA2G7<\/jats:italic>, the gene encoding Lp-PLA<jats:sub>2<\/jats:sub>, among 1258 participants from the Chinese Multi-provincial Cohort Study-Beijing Project. The Sequenom MassARRAY system, Taqman assay and direct sequencing were adopted. For the first time, the rs13218408 polymorphism was found to be significantly associated with reduced Lp-PLA<jats:sub>2<\/jats:sub> levels. We also confirmed the significant association of previously validated polymorphisms (rs1421378, rs1805018, rs16874954 and rs2216465), even after adjusting for traditional cardiovascular risk factors and for Bonferroni correction. Percentages of variance attributable to rs13218408 were 7.2% for activity and 13.3% for mass, and were secondary to those of rs16874954 (8.1% for activity and 16.9% for mass). A significant joint effect of rs13218408 and rs16874954 was observed on Lp-PLA<jats:sub>2<\/jats:sub> activity (<jats:italic>P<\/jats:italic>\u2009=\u20090.058) and mass (<jats:italic>P<\/jats:italic>\u2009=\u20090.003), with their minor alleles together linking to the largest reduction in Lp-PLA<jats:sub>2<\/jats:sub> levels (37.8% reduction in activity and 41.6% reduction in mass). Taken together, our findings show a significant association of a <jats:italic>PLA2G7<\/jats:italic> polymorphism with Lp-PLA<jats:sub>2<\/jats:sub> levels, which was previously unreported in any population. The functionality of this genetic variation deserves further investigations.<\/jats:p>","DOI":"10.1038\/srep37465","type":"journal-article","created":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T11:01:21Z","timestamp":1480590081000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A previously unreported impact of a PLA2G7 gene polymorphism on the plasma levels of lipoprotein-associated phospholipase A2 activity and mass"],"prefix":"10.1038","volume":"6","author":[{"given":"Yue","family":"Qi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhangrong","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayi","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wuxiang","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,12,1]]},"reference":[{"key":"BFsrep37465_CR1","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1161\/01.ATV.0000160551.21962.a7","volume":"25","author":"A Zalewski","year":"2005","unstructured":"Zalewski, A. & Macphee, C. Role of lipoprotein-associated phospholipase A2 in atherosclerosis: biology, epidemiology, and possible therapeutic target. Arterioscler Thromb Vasc Biol 25, 923\u2013931 (2005).","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"BFsrep37465_CR2","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1097\/CRD.0b013e3181b2434e","volume":"17","author":"H Khakpour","year":"2009","unstructured":"Khakpour, H. & Frishman, W. H. Lipoprotein-associated phospholipase A2: an independent predictor of cardiovascular risk and a novel target for immunomodulation therapy. Cardiol Rev 17, 222\u2013229 (2009).","journal-title":"Cardiol Rev"},{"key":"BFsrep37465_CR3","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1038\/nm.1870","volume":"14","author":"RL Wilensky","year":"2008","unstructured":"Wilensky, R. L. et al. Inhibition of lipoprotein-associated phospholipase A2 reduces complex coronary atherosclerotic plaque development. Nat Med 14, 1059\u20131066 (2008).","journal-title":"Nat Med"},{"key":"BFsrep37465_CR4","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1161\/CIRCULATIONAHA.108.771899","volume":"118","author":"PW Serruys","year":"2008","unstructured":"Serruys, P. W. et al. Effects of the direct lipoprotein-associated phospholipase A(2) inhibitor darapladib on human coronary atherosclerotic plaque. Circulation 118, 1172\u20131182 (2008).","journal-title":"Circulation"},{"key":"BFsrep37465_CR5","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.1016\/S0140-6736(10)60319-4","volume":"375","author":"A Thompson","year":"2010","unstructured":"Thompson, A. et al. Lipoprotein-associated phospholipase A(2) and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies. Lancet 375, 1536\u20131544 (2010).","journal-title":"Lancet"},{"key":"BFsrep37465_CR6","doi-asserted-by":"publisher","first-page":"2642","DOI":"10.2337\/dc10-1388","volume":"33","author":"A Saremi","year":"2010","unstructured":"Saremi, A. et al. Rates and determinants of coronary and abdominal aortic artery calcium progression in the Veterans Affairs Diabetes Trial (VADT). Diabetes Care 33, 2642\u20132647 (2010).","journal-title":"Diabetes Care"},{"key":"BFsrep37465_CR7","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1089\/dia.2010.0175","volume":"13","author":"GL Kinney","year":"2011","unstructured":"Kinney, G. L. et al. Lipoprotein-associated phospholipase A(2) activity predicts progression of subclinical coronary atherosclerosis. Diabetes Technol Ther 13, 381\u2013387 (2011).","journal-title":"Diabetes Technol Ther"},{"key":"BFsrep37465_CR8","doi-asserted-by":"publisher","first-page":"532","DOI":"10.5551\/jat.22772","volume":"21","author":"J Liu","year":"2014","unstructured":"Liu, J. et al. Association between the lipoprotein-associated phospholipase A2 activity and the progression of subclinical atherosclerosis. J Atheroscler Thromb 21, 532\u2013542 (2014).","journal-title":"J Atheroscler Thromb"},{"key":"BFsrep37465_CR9","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.atherosclerosis.2014.07.011","volume":"236","author":"Y Pokharel","year":"2014","unstructured":"Pokharel, Y. et al. Association between lipoprotein associated phospholipase A2 mass and subclinical coronary and carotid atherosclerosis in Retired National Football League players. Atherosclerosis 236, 251\u2013256 (2014).","journal-title":"Atherosclerosis"},{"key":"BFsrep37465_CR10","doi-asserted-by":"publisher","first-page":"1702","DOI":"10.1056\/NEJMoa1315878","volume":"370","author":"HD White","year":"2014","unstructured":"White, H. D. et al. Darapladib for preventing ischemic events in stable coronary heart disease. N Engl J Med 370, 1702\u20131711 (2014).","journal-title":"N Engl J Med"},{"key":"BFsrep37465_CR11","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1001\/jama.2014.11061","volume":"312","author":"ML O\u2032Donoghue","year":"2014","unstructured":"O\u2032Donoghue, M. L. et al. Effect of darapladib on major coronary events after an acute coronary syndrome: the SOLID-TIMI 52 randomized clinical trial. JAMA 312, 1006\u20131015 (2014).","journal-title":"JAMA"},{"key":"BFsrep37465_CR12","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.atherosclerosis.2008.08.045","volume":"205","author":"L Lenzini","year":"2009","unstructured":"Lenzini, L. et al. A twin study of heritability of plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity. Atherosclerosis 205, 181\u2013185 (2009).","journal-title":"Atherosclerosis"},{"key":"BFsrep37465_CR13","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1093\/eurheartj\/ehr372","volume":"33","author":"H Grallert","year":"2012","unstructured":"Grallert, H. et al. 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\u2013251 (2012).","journal-title":"Eur Heart J"},{"key":"BFsrep37465_CR14","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1016\/j.cca.2009.12.021","volume":"411","author":"JK Paik","year":"2010","unstructured":"Paik, J. K. et al. Effects of V279F in the Lp-PLA(2) gene on markers of oxidative stress and inflammation in Koreans. Clin Chim Acta 411, 486\u2013493 (2010).","journal-title":"Clin Chim Acta"},{"key":"BFsrep37465_CR15","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1291\/hypres.30.403","volume":"30","author":"SY Zhang","year":"2007","unstructured":"Zhang, S. Y. et al. Comprehensive evaluation of genetic and environmental factors influencing the plasma lipoprotein-associated phospholipase A2 activity in a Japanese population. Hypertens Res 30, 403\u2013409 (2007).","journal-title":"Hypertens Res"},{"key":"BFsrep37465_CR16","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/s00439-008-0587-4","volume":"125","author":"L Hou","year":"2009","unstructured":"Hou, L. et al. 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\u201320 (2009).","journal-title":"Hum Genet"},{"key":"BFsrep37465_CR17","doi-asserted-by":"publisher","first-page":"2591","DOI":"10.1001\/jama.291.21.2591","volume":"291","author":"J Liu","year":"2004","unstructured":"Liu, J. et al. Predictive value for the Chinese population of the Framingham CHD risk assessment tool compared with the Chinese Multi-Provincial Cohort Study. JAMA 291, 2591\u20132599 (2004).","journal-title":"JAMA"},{"key":"BFsrep37465_CR18","doi-asserted-by":"crossref","unstructured":"World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 310, 2191\u20132194 (2013).","DOI":"10.1001\/jama.2013.281053"},{"key":"BFsrep37465_CR19","doi-asserted-by":"publisher","first-page":"2560","DOI":"10.1001\/jama.289.19.2560","volume":"289","author":"AV Chobanian","year":"2003","unstructured":"Chobanian, A. V. et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 289, 2560\u20132572 (2003).","journal-title":"JAMA"},{"key":"BFsrep37465_CR20","doi-asserted-by":"crossref","unstructured":"Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 26 Suppl 1, S5\u201320 (2003).","DOI":"10.2337\/diacare.26.2007.S5"},{"key":"BFsrep37465_CR21","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/j.atherosclerosis.2006.02.016","volume":"190","author":"M Persson","year":"2007","unstructured":"Persson, M., Nilsson, J. A., Nelson, J. J., Hedblad, B. & Berglund, G. The epidemiology of Lp-PLA(2): distribution and correlation with cardiovascular risk factors in a population-based cohort. Atherosclerosis 190, 388\u2013396 (2007).","journal-title":"Atherosclerosis"},{"key":"BFsrep37465_CR22","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1093\/ajcp\/20.11_ts.1059","volume":"20","author":"S Levey","year":"1950","unstructured":"Levey, S. & Jennings, E. R. The use of control charts in the clinical laboratory. Am J Clin Pathol 20, 1059\u20131066 (1950).","journal-title":"Am J Clin Pathol"},{"key":"BFsrep37465_CR23","doi-asserted-by":"publisher","first-page":"e1000928","DOI":"10.1371\/journal.pgen.1000928","volume":"6","author":"S Suchindran","year":"2010","unstructured":"Suchindran, S. et al. Genome-wide association study of Lp-PLA(2) activity and mass in the Framingham Heart Study. PLoS Genet 6, e1000928 (2010).","journal-title":"PLoS Genet"},{"key":"BFsrep37465_CR24","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1161\/CIRCULATIONAHA.109.923383","volume":"121","author":"JP Casas","year":"2010","unstructured":"Casas, J. P. et al. 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\u20132293 (2010).","journal-title":"Circulation"},{"key":"BFsrep37465_CR25","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/j.thromres.2010.09.009","volume":"126","author":"Q Wang","year":"2010","unstructured":"Wang, Q. et al. PLA2G7 gene polymorphisms and coronary heart disease risk: a meta-analysis. Thromb Res 126, 498\u2013503 (2010).","journal-title":"Thromb Res"},{"key":"BFsrep37465_CR26","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1093\/bioinformatics\/bth457","volume":"21","author":"JC Barrett","year":"2005","unstructured":"Barrett, J. C., Fry, B., Maller, J. & Daly, M. J. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21, 263\u2013265 (2005).","journal-title":"Bioinformatics"},{"key":"BFsrep37465_CR27","unstructured":"Gauderman, W. J. & Morrison, J. QUANTO 1.1: A computer program for power and sample size calculations for genetic-epidemiology studies. http:\/\/hydra.usc.edu\/gxe (2006)."},{"key":"BFsrep37465_CR28","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.1172\/JCI113818","volume":"82","author":"M Miwa","year":"1988","unstructured":"Miwa, M. et al. Characterization of serum platelet-activating factor (PAF) acetylhydrolase. Correlation between deficiency of serum PAF acetylhydrolase and respiratory symptoms in asthmatic children. J Clin Invest 82, 1983\u20131991 (1988).","journal-title":"J Clin Invest"},{"key":"BFsrep37465_CR29","doi-asserted-by":"publisher","first-page":"2784","DOI":"10.1172\/JCI118733","volume":"97","author":"DM Stafforini","year":"1996","unstructured":"Stafforini, D. M. et al. Platelet-activating factor acetylhydrolase deficiency. A missense mutation near the active site of an anti-inflammatory phospholipase. J Clin Invest 97, 2784\u20132791 (1996).","journal-title":"J Clin Invest"},{"key":"BFsrep37465_CR30","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1007\/s10038-004-0151-6","volume":"49","author":"M Ishihara","year":"2004","unstructured":"Ishihara, M. et al. Functional impairment of two novel mutations detected in lipoprotein-associated phospholipase A2 (Lp-PLA2) deficiency patients. J Hum Genet 49, 302\u2013307 (2004).","journal-title":"J Hum Genet"},{"key":"BFsrep37465_CR31","doi-asserted-by":"publisher","first-page":"25935","DOI":"10.1074\/jbc.R400008200","volume":"279","author":"K Zhang","year":"2004","unstructured":"Zhang, K. & Kaufman, R. J. Signaling the unfolded protein response from the endoplasmic reticulum. J Biol Chem 279, 25935\u201325938 (2004).","journal-title":"J Biol Chem"},{"key":"BFsrep37465_CR32","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/j.clinbiochem.2014.01.010","volume":"47","author":"X Liu","year":"2014","unstructured":"Liu, X. et al. Association of PLA2G7 gene polymorphisms with ischemic stroke in northern Chinese Han population. Clin Biochem 47, 404\u2013408 (2014).","journal-title":"Clin Biochem"},{"key":"BFsrep37465_CR33","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1111\/j.1538-7836.2008.03216.x","volume":"7","author":"MM Hoffmann","year":"2009","unstructured":"Hoffmann, M. M. et al. Genetic variants and haplotypes of lipoprotein associated phospholipase A2 and their influence on cardiovascular disease (The Ludwigshafen Risk and Cardiovascular Health Study). J Thromb Haemost 7, 41\u201348 (2009).","journal-title":"J Thromb Haemost"},{"key":"BFsrep37465_CR34","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1111\/j.1538-7836.2006.01895.x","volume":"4","author":"PY Liu","year":"2006","unstructured":"Liu, P. Y. et al. 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\u20131028 (2006).","journal-title":"J Thromb Haemost"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep37465.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep37465","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep37465.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T02:33:09Z","timestamp":1672885989000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep37465"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,1]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,23]]}},"alternative-id":["BFsrep37465"],"URL":"https:\/\/doi.org\/10.1038\/srep37465","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,1]]},"assertion":[{"value":"15 April 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 October 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"37465"}}