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Endocrine, Metabolic & Immune Disorders - Drug Targets

Author(s): Safoura Khajeniazi*, Abdoljalal Marjani*, Raheleh Shakeri and Safoura Hakimi

DOI: 10.2174/1871530319666190528111225

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Polymorphism of Secretary PLA2G2A Gene Associated with Its Serum Level in Type2 Diabetes Mellitus Patients in Northern Iran

Page: [1192 - 1197] Pages: 6

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Abstract

Background: Inflammation may occur in Type2 diabetes mellitus. sPLA2 is among the factors that contribute to the activation of pathways involved in inflammation. Several agents affect serum sPLA2 level, one of which is genetic diversity.

Objective: The current study was performed to determine whether there is a relationship between sPLA2 gene (−763C > G) polymorphism and circulating sPLA2 level in patients with Type 2 diabetes.

Methods: DNA was extracted from blood samples and used for the amplification of sPLA2 gene using ARMS-PCR.

Results: A statistical analysis using SPSS (version 16) revealed a significant correlation between −763C > G sPLA2 gene polymorphisms and the disease incidence in patients with T2DM. Among the three possible genotypes (GG, CC, and CG), CG genotype was found to have a higher frequency(53%) in T2DM patients. GG and CC genotypes frequencies were 20 and 27%, respectively. In healthy individuals, the frequencies of CC, GG, and GC genotypes were 77, 9.8% and 13.2%, respectively). Patients with genotype GG had the highest level of sPLA2. We showed that C>G polymorphism at position– 763 is associated with a high level of sPLA2 in both T2DM patients and healthy individuals. The average of sPLA2 circulating level was (170.48± 84.90), (106.62 ± 74.31), in patients and normal individuals, respectively.

Conclusion: Our findings show that sPLA2 serum level is significantly higher in patients with T2DM disease than that in healthy individuals.

Keywords: Secretary phospholipase A2, type 2 diabetes mellitus, polymorphism, gene expression, inflammation, ARMS PCR.

Graphical Abstract

[1]
Huang, Q.Y.; Cheng, M.R.; Ji, S.L. Linkage and association studies of the susceptibility genes for type 2 diabetes. Yi Chuan Xue Bao, 2006, 33(7), 573-589.
[http://dx.doi.org/10.1016/S0379-4172(06)60087-5] [PMID: 16875315]
[2]
Adibhatla, R.M.; Hatcher, J.F. Phospholipase A(2), reactive oxygen species, and lipid peroxidation in CNS pathologies. BMB Rep., 2008, 41(8), 560-567.
[http://dx.doi.org/10.5483/BMBRep.2008.41.8.560] [PMID: 18755070]
[3]
Triggiani, M.; Granata, F.; Frattini, A.; Marone, G. Activation of human inflammatory cells by secreted phospholipases A2. Biochim. Biophys. Acta, 2006, 1761(11), 1289-1300.
[http://dx.doi.org/10.1016/j.bbalip.2006.07.003] [PMID: 16952481]
[4]
Six, D.A.; Dennis, E.A. The expanding superfamily of phospholipase A(2) enzymes: classification and characterization. Biochim. Biophys. Acta, 2000, 1488(1-2), 1-19.
[http://dx.doi.org/10.1016/S1388-1981(00)00105-0] [PMID: 11080672]
[5]
Kramer, R.M.; Hession, C.; Johansen, B.; Hayes, G.; McGray, P.; Chow, E.P.; Tizard, R.; Pepinsky, R.B. Structure and properties of a human non-pancreatic phospholipase A2. J. Biol. Chem., 1989, 264(10), 5768-5775.
[PMID: 2925633]
[6]
Exeter, H.J.; Folkersen, L.; Palmen, J.; Franco-Cereceda, A.; Cooper, J.A.; Kalea, A.Z.; Hooft, F.V.; Eriksson, P.; Humphries, S.E.; Talmud, P.J. Functional analysis of two PLA2G2A variants associated with secretory phospholipase A2-IIA levels. PLoS One, 2012, 7(7)e41139
[http://dx.doi.org/10.1371/journal.pone.0041139] [PMID: 22879865]
[7]
Friedman, J.E.; Kirwan, J.P.; Jing, M.; Presley, L.; Catalano, P.M. Increased skeletal muscle tumor necrosis factor-α and impaired insulin signaling persist in obese women with gestational diabetes mellitus 1 year postpartum. Diabetes, 2008, 57(3), 606-613.
[http://dx.doi.org/10.2337/db07-1356] [PMID: 18083784]
[8]
Cai, D.; Yuan, M.; Frantz, D.F.; Melendez, P.A.; Hansen, L.; Lee, J.; Shoelson, S.E. Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-kappaB. Nat. Med., 2005, 11(2), 183-190.
[http://dx.doi.org/10.1038/nm1166] [PMID: 15685173]
[9]
Shakir, K.M.M.; Reed, H. O’BRIAN, J.T. Decreased Phospholipase A2 Activity in Plasma and Liver in Uncontrolled Diabetes Mellitus. Diabetes, 1986, 35, 403-410.
[http://dx.doi.org/10.2337/diab.35.4.403] [PMID: 3956877]
[10]
Hurt-Camejo, E.; Camejo, G.; Peilot, H.; Oörni, K.; Kovanen, P. Phospholipase A(2) in vascular disease. Circ. Res., 2001, 89(4), 298-304.
[http://dx.doi.org/10.1161/hh1601.095598] [PMID: 11509445]
[11]
Nevalainen, T.J.; Haapamäki, M.M.; Grönroos, J.M. Roles of secretory phospholipases A(2) in inflammatory diseases and trauma. Biochim. Biophys. Acta, 2000, 1488(1-2), 83-90.
[http://dx.doi.org/10.1016/S1388-1981(00)00112-8] [PMID: 11080679]
[12]
Peilot, H.; Rosengren, B.; Bondjers, G.; Hurt-Camejo, E. Interferon-gamma induces secretory group IIA phospholipase A2 in human arterial smooth muscle cells. Involvement of cell differentiation, STAT-3 activation, and modulation by other cytokines. J. Biol. Chem., 2000, 275(30), 22895-22904.
[http://dx.doi.org/10.1074/jbc.M002783200] [PMID: 10811652]
[13]
Tremblay, B.L.; Cormier, H.; Rudkowska, I.; Lemieux, S.; Couture, P.; Vohl, M.C. Association between polymorphisms in phospholipase A2 genes and the plasma triglyceride response to an n-3 PUFA supplementation: a clinical trial. Lipids Health Dis., 2015, 14, 12.
[http://dx.doi.org/10.1186/s12944-015-0009-2] [PMID: 25889305]
[14]
Rosenson, R.S.; Stafforini, D.M. Modulation of oxidative stress, inflammation, and atherosclerosis by lipoprotein-associated phospholipase A2. J. Lipid Res., 2012, 53(9), 1767-1782.
[http://dx.doi.org/10.1194/jlr.R024190] [PMID: 22665167]
[15]
Eckel, R.H.; Wassef, M.; Chait, A.; Sobel, B.; Barrett, E.; King, G.; Lopes-Virella, M.; Reusch, J.; Ruderman, N.; Steiner, G.; Vlassara, H. Prevention Conference VI: Diabetes and Cardiovascular Disease: Writing Group II: pathogenesis of atherosclerosis in diabetes. Circulation, 2002, 105(18), e138-e143.
[http://dx.doi.org/10.1161/01.CIR.0000013954.65303.C5] [PMID: 11994264]
[16]
Miller, S.A.; Dykes, D.D.; Polesky, H.F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res., 1988, 16(3), 1215.
[http://dx.doi.org/10.1093/nar/16.3.1215] [PMID: 3344216]
[17]
Dutour, A.; Achard, V.; Sell, H.; Naour, N.; Collart, F.; Gaborit, B.; Silaghi, A.; Eckel, J.; Alessi, M.C.; Henegar, C.; Clément, K. Secretory type II phospholipase A2 is produced and secreted by epicardial adipose tissue and overexpressed in patients with coronary artery disease. J. Clin. Endocrinol. Metab., 2010, 95(2), 963-967.
[http://dx.doi.org/10.1210/jc.2009-1222] [PMID: 20008021]
[18]
Divchev, D.; Schieffer, B. The secretory phospholipase A2 group IIA: a missing link between inflammation, activated renin-angiotensin system, and atherogenesis? Vasc. Health Risk Manag., 2008, 4(3), 597-604.
[http://dx.doi.org/10.2147/VHRM.S2008] [PMID: 18827909]
[19]
Moses, G.S.; Jensen, M.D.; Lue, L.F.; Walker, D.G.; Sun, A.Y.; Simonyi, A.; Sun, G.Y. Secretory PLA2-IIA: a new inflammatory factor for Alzheimer’s disease. J. Neuroinflammation, 2006, 3, 28.
[http://dx.doi.org/10.1186/1742-2094-3-28] [PMID: 17026770]
[20]
Maes, M.; Kubera, M.; Obuchowiczwa, E.; Goehler, L.; Brzeszcz, J. Depression’s multiple comorbidities explained by (neuro)inflammatory and oxidative & nitrosative stress pathways. Neuroendocrinol. Lett., 2011, 32(1), 7-24. b.
[PMID: 21407167]
[21]
Paranthaman, R.; Greenstein, A.S.; Burns, A.S.; Cruickshank, J.K.; Heagerty, A.M.; Jackson, A.; Malik, R.A.; Scott, M.L.; Baldwin, R.C. Vascular function in older adults with depressive disorder. Biol. Psychiatry, 2010, 68(2), 133-139.
[http://dx.doi.org/10.1016/j.biopsych.2010.04.017] [PMID: 20609838]
[22]
Schaeffer, E.L.; da Silva, E.R. Novaes, Bde.A.; Skaf, H.D.; Gattaz, W.F. Differential roles of phospholipases A2 in neuronal death and neurogenesis: implications for Alzheimer disease. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2010, 34(8), 1381-1389.
[http://dx.doi.org/10.1016/j.pnpbp.2010.08.019] [PMID: 20804810]
[23]
Leitinger, N.; Watson, A.D.; Hama, S.Y.; Ivandic, B.; Qiao, J.H.; Huber, J.; Faull, K.F.; Grass, D.S.; Navab, M.; Fogelman, A.M.; de Beer, F.C.; Lusis, A.J.; Berliner, J.A. Role of group II secretory phospholipase A2 in atherosclerosis: 2. Potential involvement of biologically active oxidized phospholipids. Arterioscler. Thromb. Vasc. Biol., 1999, 19(5), 1291-1298.
[http://dx.doi.org/10.1161/01.ATV.19.5.1291] [PMID: 10323782]
[24]
Kaneko, K.; Sakai, M.; Matsumura, T.; Biwa, T.; Furukawa, N.; Shirotani, T. Group-II phospholipase A(2) enhances oxidized low density lipoprotein-induced macrophage growth through enhancement of GM-colony stimulating factor (CSF) release. Atherosclerosis, 2000, 153, 37-46.
[http://dx.doi.org/10.1016/S0021-9150(00)00391-9] [PMID: 11058698]
[25]
Wootton, P.; Drenos, F.; Cooper, J.; Thompson, S.; Stephens, J.; Hurt-Camejo, E.; Wiklund, O. Tagging-SNP haplotype analysis of the secretory PLA2IIa gene PLA2G2A shows strong association with serum levels of sPLA2IIa: results from the UDACS study., 2006. 15.
[26]
Sahmani, M.; Darabi, M.; Darabi, M.; Dabaghi, T.; Alizadeh, S.A.; Najafipour, R. The 763C>G Polymorphism of The Secretory PLA2IIa Gene Is Associated with Endometriosis in Iranian Women. Int. J. Fertil. Steril., 2015, 8(4), 437-444.
[PMID: 25780526]
[27]
Lin, X.H.; Xu, M.T.; Tang, J.Y.; Mai, L.F.; Wang, X.Y.; Ren, M.; Yan, L. Effect of intensive insulin treatment on plasma levels of lipoprotein-associated phospholipase A2 and secretory phospholipase A2 in patients with newly diagnosed type 2 diabetes. Lipids Health Dis., 2016, 15(1), 203.
[http://dx.doi.org/10.1186/s12944-016-0368-3] [PMID: 27881128]
[28]
Holmes, M.; Simon, T.; Exeter, H.; Folkersen, L.; Asselbergs, F.; Guardiola, M. Secretory Phospholipase A2-IIA and Cardiovascular Disease. J. Am. Coll. Cardiol., 2013, 62, 1966-1976.
[http://dx.doi.org/10.1016/j.jacc.2013.06.044] [PMID: 24315920]
[29]
Shuvalova, Y.A.; Khasanova, Z.B.; Kaminnaya, V.I.; Samoilova, E.V.; Korotaeva, A.A.; Rubanovich, A.V.; Kaminnyi, A.I. The association of PLA2G2A single nucleotide polymorphisms with type IIa secretory phospholipase A2 level but not its activity in patients with stable coronary heart disease. Gene, 2015, 564(1), 29-34.
[http://dx.doi.org/10.1016/j.gene.2015.03.030] [PMID: 25794429]
[30]
Boyanovsky, B.B.; Webb, N.R. Biology of secretory phospholipase A2. Cardiovasc. Drugs Ther., 2009, 23(1), 61-72.
[http://dx.doi.org/10.1007/s10557-008-6134-7] [PMID: 18853244]
[31]
Leung, S.Y.; Chen, X.; Chu, K.M.; Yuen, S.T.; Mathy, J.; Ji, J.; Chan, A.S.; Li, R.; Law, S.; Troyanskaya, O.G.; Tu, I.P.; Wong, J.; So, S.; Botstein, D.; Brown, P.O. Phospholipase A2 group IIA expression in gastric adenocarcinoma is associated with prolonged survival and less frequent metastasis. Proc. Natl. Acad. Sci. USA, 2002, 99(25), 16203-16208.
[http://dx.doi.org/10.1073/pnas.212646299] [PMID: 12456890]