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Disease Report for: Suceptibility to asthma and atopy, Platelet-activating factor acetylhydrolase (PLA2G7) deficiency (PAFAD) coronary artery disease risk factor

Alternative name(s)|Phospholipase A2 group VII deficiency
PLA2G7 deficiency
PAFAH deficiency
Platelet-activating factor acetylhydrolase deficiency
Mutation|9 mutations (e.g. : A379V_human-PLA2G7, D166E_human-PLA2G7, I198T_human-PLA2G7... more)
OMIM: |601690, 600807, 147050, 614278

(from OMIM) Platelet-activating factor (PAF) is a biologically active phospholipid with diverse potent biologic effects. Stafforini et al. (1996) noted that PAF has been implicated as a mediator of physiologic processes, such as signaling and activation of proinflammatory cells, alteration of vascular permeability, and stimulation of glycogen metabolism among many others. In addition to its role as a physiologic mediator, PAF is associated with a pathology of several human diseases, particularly allergy and inflammation, affecting the respiratory, vascular, digestive, and reproductive systems.PAF is degraded to inactive products by hydrolysis of the acetyl group at the sn-2 position to produce the biologically inactive products LYSO-PAF and acetate. This reaction is catalyzed by PAF acetylhydrolase. Miwa et al. (1988) described an autosomal recessive form of PAF acetylhydrolase deficiency which has been observed only in Japanese. PAF acetylhydrolase activity was absent in 4% of the Japanese population. Previously known loss-of-function mutations were not found but 3 common variants of the PAFAH gene were identified: arg92 to his (exon 4), ile198 to thr (exon 7), and ala379 to val (exon 11). The variant allele thr198 was found to be highly associated with total IgE concentrations in an atopic population and with 'asthma' in an asthmatic population. The variant allele val379 was found to be highly associated with 'specific sensitization' in the atopic population and with 'asthma' in the asthmatic population. There is an association between lipoprotein-associated phospholipase A2 gene polymorphism and coronary artery disease

    Title: Association Lp-PLA2 Gene Polymorphisms with Coronary Heart Disease
    Ma S, Ding L, Cai M, Chen L, Yan B, Yang J
    Ref: Dis Markers, 2022:9775699, 2022 : PubMed


    Title: Structural Modeling of Wild and Mutant Forms of Human Plasma Platelet Activating Factor-Acetyl Hydrolase Enzyme
    Khan MI, Hariprasad G
    Ref: J Inflamm Res, 13:1125, 2020 : PubMed


    Title: Phospholipase A2 is an Inflammatory Predictor in Cardiovascular Diseases: Is there any Spacious Room to Prove the Causation?
    Santoso A, Heriansyah T, Rohman MS
    Ref: Curr Cardiol Rev, 16:3, 2020 : PubMed


    Title: The association between the D166E polymorphism of the lipoprotein associated phospholipase A2 and risk of myocardial infarction
    Zhang MM, Zhang CG, Yang CJ, Zhao P, Li YL
    Ref: Eur Rev Med Pharmacol Sci, 23:3960, 2019 : PubMed


    Title: Interaction between nonsynonymous polymorphisms in PLA2G7 gene and smoking on the risk of coronary heart disease in a Chinese population
    Chi Y, Shi C, Zhang X, Xi Y
    Ref: J Thromb Thrombolysis, 46:125, 2018 : PubMed


    Title: Genetic invalidation of Lp-PLA(2) as a therapeutic target: Large-scale study of five functional Lp-PLA(2)-lowering alleles
    Gregson JM, Freitag DF, Surendran P, Stitziel NO, Chowdhury R, Burgess S, Kaptoge S, Gao P, Staley JR and Danesh J <51 more author(s)>
    Ref: Eur J Prev Cardiol, 24:492, 2017 : PubMed


    Title: Effects of overweight and the PLA2G7 V279F polymorphism on the association of age with systolic blood pressure
    Kim M, Yoo HJ, Jang HY, Lee SH, Lee JH
    Ref: PLoS ONE, 12:e0173611, 2017 : PubMed


    Title: Association of Lp-PLA2 G994T gene polymorphism with risk of ischemic stroke in Chinese population
    Ni J, Gu H, Hu W, Zhou F, Zhu X, Wang K
    Ref: J Biochem Mol Toxicol, 31:, 2017 : PubMed


    Title: Associations between four types of single-nucleotide polymorphisms in PLA2G7 gene and clinical atherosclerosis: a meta-analysis
    Santoso A, Maulana R, Alzahra F, Maghfirah I, Putrinarita AD, Heriansyah T
    Ref: Am J Cardiovasc Dis, 7:122, 2017 : PubMed


    Title: Association between Lp-PLA2 and coronary heart disease in Chinese patients
    Yang L, Liu Y, Wang S, Liu T, Cong H
    Ref: J Internal Medicine Res, 45:159, 2017 : PubMed


    Title: Pharmacogenetic meta-analysis of baseline risk factors, pharmacodynamic, efficacy and tolerability endpoints from two large global cardiovascular outcomes trials for darapladib
    Yeo A, Li L, Warren L, Aponte J, Fraser D, King K, Johansson K, Barnes A, Macphee C and Waterworth D <6 more author(s)>
    Ref: PLoS ONE, 12:e0182115, 2017 : PubMed


    Title: Val279Phe variant of Lp-PLA2 is a risk factor for a subpopulation of Indonesia patients with acute myocardial infarction
    Cahyaningtias M, Rohman MS, Widodo, Wahjono Adi A, Yuda R, Indrayana Y, Putri JF, Rusdianto, Lukitasari M, Hendrawan D
    Ref: Genes Dis, 3:289, 2016 : PubMed


    Title: Association between Ala379Val polymorphism of lipoprotein-associated phospholipase A2 and migraine without aura in Iranian population
    Haghdoost F, Gharzi M, Faez F, Hosseinzadeh E, Tajaddini M, Ra Ei L, Asgari F, Banihashemi M, Masjedi SS and Haghjooy-Javanmard S <1 more author(s)>
    Ref: Iran Journal of Neurology, 15:80, 2016 : PubMed


    Title: A phenome-wide association study of a lipoprotein-associated phospholipase A2 loss-of-function variant in 90 000 Chinese adults
    Millwood IY, Bennett DA, Walters RG, Clarke R, Waterworth D, Johnson T, Chen Y, Yang L, Guo Y and Chen Z <10 more author(s)>
    Ref: Int J Epidemiol, 45:1588, 2016 : PubMed


    Title: Naturally Occurring Missense Mutation in Plasma PAF-AH Among the Japanese Population
    Karasawa K
    Ref: Enzymes, 38:117, 2015 : PubMed


    Title: Carriage of the V279F null allele within the gene encoding Lp-PLA(2) is protective from coronary artery disease in South Korean males
    Jang Y, Waterworth D, Lee JE, Song K, Kim S, Kim HS, Park KW, Cho HJ, Oh IY and Mooser V <12 more author(s)>
    Ref: PLoS ONE, 6:e18208, 2011 : PubMed


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


    Title: Lipoprotein-associated phospholipase A2 gene V279F polymorphisms and coronary heart disease: a meta-analysis
    Zheng GH, Chen HY, Xiong SQ, Chu JF
    Ref: Mol Biol Rep, 38:4089, 2011 : PubMed


    Title: Identification of the G994T polymorphism in exon 9 of plasma platelet-activating factor acetylhydrolase gene as a risk factor for polycystic ovary syndrome
    Fan P, Liu Hw, Wang XS, Zhang F, Song Q, Li Q, Wu HM, Bai H
    Ref: Hum Reprod, 25:1288, 2010 : PubMed


    Title: PLA2G7 gene polymorphisms and coronary heart disease risk: a meta-analysis
    Wang Q, Hao Y, Mo X, Wang L, Lu X, Huang J, Cao J, Li H, Gu D
    Ref: Thromb Res, 126:498, 2010 : PubMed


    Title: Genetic variants and haplotypes of lipoprotein associated phospholipase A2 and their influence on cardiovascular disease (The Ludwigshafen Risk and Cardiovascular Health Study)
    Hoffmann MM, Winkler K, Renner W, Winkelmann BR, Seelhorst U, Wellnitz B, Boehm BO, Marz W
    Ref: J Thromb Haemost, 7:41, 2009 : PubMed


    Title: 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
    Hou L, Chen S, Yu H, Lu X, Chen J, Wang L, Huang J, Fan Z, Gu D
    Ref: Hum Genet, 125:11, 2009 : PubMed


    Title: Inter-individual variability of plasma PAF-acetylhydrolase activity in ARDS patients and PAFAH genotype
    Li S, Stuart L, Zhang Y, Meduri GU, Umberger R, Yates CR
    Ref: J Clin Pharm Ther, 34:447, 2009 : PubMed


    Title: Effects of G994T in the Lp-PLA2 gene on the plasma oxidized LDL level and carotid intima-media thickness in Japanese: the Shimane study
    Wang T, Karino K, Yamasaki M, Zhang Y, Masuda J, Yamaguchi S, Shiwaku K, Nabika T
    Ref: Am J Hypertens, 22:742, 2009 : PubMed


    Title: Comprehensive genetic analysis of the platelet activating factor acetylhydrolase (PLA2G7) gene and cardiovascular disease in case-control and family datasets
    Sutton BS, Crosslin DR, Shah SH, Nelson SC, Bassil A, Hale AB, Haynes C, Goldschmidt-Clermont PJ, Vance JM and Hauser ER <3 more author(s)>
    Ref: Hum Mol Genet, 17:1318, 2008 : PubMed


    Title: Comprehensive evaluation of genetic and environmental factors influencing the plasma lipoprotein-associated phospholipase A2 activity in a Japanese population
    Zhang SY, Shibata H, Karino K, Wang BY, Kobayashi S, Masuda J, Nabika T
    Ref: Hypertens Res, 30:403, 2007 : PubMed


    Title: The Val279Phe variant of the lipoprotein-associated phospholipase A2 gene is associated with catalytic activities and cardiovascular disease in Korean men
    Jang Y, Kim OY, Koh SJ, Chae JS, Ko YG, Kim JY, Cho H, Jeong TS, Lee WS and Lee JH <1 more author(s)>
    Ref: J Clinical Endocrinology Metab, 91:3521, 2006 : PubMed


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


    Title: Association of platelet-activating factor acetylhydrolase gene polymorphism with premature coronary artery disease in Turkish patients
    Sekuri C, Cam FS, Tengiz I, Ercan E, Bayturan O, Berdeli A
    Ref: Anadolu Kardiyol Derg, 6:132, 2006 : PubMed


    Title: Vasospastic angina and microvascular angina are differentially influenced by PON1 A632G polymorphism in the Japanese
    Mashiba J, Koike G, Kamiunten H, Ikeda M, Sunagawa K
    Ref: Circ J, 69:1466, 2005 : PubMed


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


    Title: Association between the Ala379Val variant of the lipoprotein associated phospholipase A2 and risk of myocardial infarction in the north and south of Europe
    Abuzeid AM, Hawe E, Humphries SE, Talmud PJ
    Ref: Atherosclerosis, 168:283, 2003 : PubMed


    Title: Association of plasma PAF acetylhydrolase gene polymorphism with IMT of carotid arteries in Japanese type 2 diabetic patients
    Yamamoto I, Fujitsu J, Nohnen S, Igarashi T, Motomura T, Inaba M, Tsubakimori S, Azuma J
    Ref: Diabetes Res Clin Pract, 59:219, 2003 : PubMed


    Title: Evidence for the existence of the PAF acetylhydrolase mutation (Val279Phe) in non-Japanese populations: a preliminary study in Turkey, Azerbaijan, and Kyrgyzstan
    Balta G, Gurgey A, Kudayarov DK, Tunc B, Altay C
    Ref: Thromb Res, 101:231, 2001 : PubMed


    Title: The Ile198Thr and Ala379Val variants of plasmatic PAF-acetylhydrolase impair catalytical activities and are associated with atopy and asthma
    Kruse S, Mao XQ, Heinzmann A, Blattmann S, Roberts MH, Braun S, Gao PS, Forster J, Kuehr J and Deichmann KA <2 more author(s)>
    Ref: American Journal of Human Genetics, 66:1522, 2000 : PubMed


    Title: Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. West of Scotland Coronary Prevention Study Group
    Packard CJ, O'Reilly DS, Caslake MJ, McMahon AD, Ford I, Cooney J, Macphee CH, Suckling KE, Krishna M and Lowe GD <2 more author(s)>
    Ref: N Engl J Med, 343:1148, 2000 : PubMed


    Title: Platelet-activating factor acetylhydrolase gene mutation in Japanese children with Escherichia coli O157-associated hemolytic uremic syndrome
    Xu H, Iijima K, Shirakawa T, Shiozawa S, Miwa M, Yamaoka K, Kawamura N, Nakamura H, Yoshikawa N
    Ref: Am J Kidney Dis, 36:42, 2000 : PubMed


    Title: Deficiency of platelet-activating factor acetylhydrolase is a severity factor for asthma
    Stafforini DM, Numao T, Tsodikov A, Vaitkus D, Fukuda T, Watanabe N, Fueki N, McIntyre TM, Zimmerman GA and Prescott SM <1 more author(s)>
    Ref: J Clinical Investigation, 103:989, 1999 : PubMed


    Title: Role of platelet-activating factor acetylhydrolase gene mutation in Japanese childhood IgA nephropathy
    Tanaka R, Iijima K, Xu H, Inoue Y, Murakami R, Shirakawa T, Nishiyama K, Miwa M, Shiozawa S and Yoshikawa N <1 more author(s)>
    Ref: Am J Kidney Dis, 34:289, 1999 : PubMed


    Title: A genome-wide search for linkage to asthma. German Asthma Genetics Group
    Wjst M, Fischer G, Immervoll T, Jung M, Saar K, Rueschendorf F, Reis A, Ulbrecht M, Gomolka M and Wichmann HE <18 more author(s)>
    Ref: Genomics, 58:1, 1999 : PubMed


    Title: Genome-wide search for asthma susceptibility loci in a founder population. The Collaborative Study on the Genetics of Asthma
    Ober C, Cox NJ, Abney M, Di Rienzo A, Lander ES, Changyaleket B, Gidley H, Kurtz B, Lee J and Parry R <7 more author(s)>
    Ref: Hum Mol Genet, 7:1393, 1998 : PubMed


    Title: Platelet-activating factor acetylhydrolase gene mutation in Japanese nephrotic children
    Xu H, Iijima K, Shiozawa S, Tanaka SS, Inoue Y, Shirakawa T, Nishiyama K, Miwa M, Nakamura H, Yoshikawa N
    Ref: Kidney Int, 54:1867, 1998 : PubMed


    Title: Systematic screening of the LDL-PLA2 gene for polymorphic variants and case-control analysis in schizophrenia
    Bell R, Collier DA, Rice SQ, Roberts GW, Macphee CH, Kerwin RW, Price J, Gloger IS
    Ref: Biochemical & Biophysical Research Communications, 241:630, 1997 : PubMed


    Title: A mutation in plasma platelet-activating factor acetylhydrolase (Val279-->Phe) is a genetic risk factor for stroke
    Hiramoto M, Yoshida H, Imaizumi T, Yoshimizu N, Satoh K
    Ref: Stroke, 28:2417, 1997 : PubMed


    Title: Genetics reveals importance of platelet activating factor in asthma and possibly other inflammatory states
    Nadel JA
    Ref: J Clinical Investigation, 97:2689, 1996 : PubMed


    Title: Platelet-activating factor acetylhydrolase deficiency. A missense mutation near the active site of an anti-inflammatory phospholipase
    Stafforini DM, Satoh K, Atkinson DL, Tjoelker LW, Eberhardt C, Yoshida H, Imaizumi T, Takamatsu S, Zimmerman GA and Prescott SM <2 more author(s)>
    Ref: J Clinical Investigation, 97:2784, 1996 : PubMed


    Title: Anti-inflammatory properties of a platelet-activating factor acetylhydrolase
    Tjoelker LW, Wilder C, Eberhardt C, Stafforini DM
    Ref: Nature, 374:549, 1995 : PubMed


    Title: Characterization of serum platelet-activating factor (PAF) acetylhydrolase. Correlation between deficiency of serum PAF acetylhydrolase and respiratory symptoms in asthmatic children
    Miwa M, Miyake T, Yamanaka T, Sugatani J, Suzuki Y, Sakata S, Araki Y, Matsumoto M
    Ref: J Clinical Investigation, 82:1983, 1988 : PubMed


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