Merih ÖZGEN, Didem Turgut COŞAN, Zeliha ATİK, Faruk SAYDAM, Emine ÇOLAK, Ahu SOYOCAK, Fulya DOĞANER, Funda BERKAN, İrfan DEĞİRMENCİ, FEZAN MUTLU

Postmenopozal Osteoporozda Paraoksonaz 1 L55M ve Q192R Polimorfizminin İ lişkisinin Değ erlendirilmesi

Osteoporoz, toplumda yaygın görünen, kemik mikro mimarisinde bozulma ve düşük kemik kütlesi ile karakterize sistemik bir hastalıktır. Çalışmamızın amacı paraoksonaz (PON1) geninin 584A>G(Gln192Arg) ve 172T>A(Leu55Met) polimorfizmleri ile postmenopozal osteoporoz ile ilişkisinin olup olmadığını saptamaktır. Eskişehir Osmangazi Üniversitesi Tıp Fakültesi Fiziksel Tıp ve Rehabilitasyon Anabilim Dalı Kliniği’nde takipli 143 postmenopozal osteoporozu olan ve 102 sağlıklı kadın çalışmaya dahil edildi. Çalışma retrospektif olarak planlandı. Genotipler alel-spesifik DNA primeri ve floresan özellikli DNA probu kullanılarak qPCR cihazında (The Applied Biosystems® StepOne™) belirlendi. PON1 584A>G polimorfizminin genotip ve alel frekanslarında gruplar arasında istatistiksel olarak anlamlı bir fark bulunmamıştır (p=0.362 ve p=0.318). PON1 172T>A polimorfizminin genotip ve alel frekansları karşılaştırıldığında ise, sağlıklı bireylere göre postmenopozal osteoporozu olanlarda T alelinin istatistiksel olarak anlamlı derecede yüksek bulunduğu (sırasıyla p

Evaluation of the Relationship of Paraoxonase 1 L55M and Q192R Polymorphism in Postmenopausal Osteoporosis

Osteoporosis is a systemic disease which is common in society, characterized by bone micro-architecture deterioration and low bone mass. The aim of our study was to determine whether paraoxonase 1 (PON1) gene correlates with 584A>G (Gln192Arg) and 172T>A (Leu55Met) polymorphisms with postmenopausal osteoporosis. A total of 143 postmenopausal osteoporosis and 102 healthy women who were followed up in Eskişehir Osmangazi University Faculty of Medicine, Department of Physical Medicine and Rehabilitation were included in the study. The study was planned retrospectively. Genotypes were identified on the qPCR (The Applied Biosystems® StepOne ™) using the allele-specific DNA primer and fluorescent-specific DNA probe. There was no statistically significant difference between the groups in the genotype and allele frequencies of PON1 584A>G polymorphism (p=0.362 and p= 0.318). When the genotype and allele frequencies of PON1 172T>A polymorphism were compared, it was observed that T allele was significantly higher in postmenopausal osteoporosis than healthy subjects (p

PDF

___

1. Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R, Reginster JY, et al. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 2013;24:23-57.
2. Zajickova K, Zofkova I. Osteoporosis: Genetic analysis of multifactorial disease. Endocr Regul 2003;37:31-44.
3. Williams FM, Spector TD. The genetics of osteoporosis. Acta Reumatol Port 2007;32:231-40.
4. Rizzoli R, Bonjour JP, Ferrari SL. Osteoporosis, genetics and hormones. J Mol Endocrinol 2001;26:79-94.
5. Uitterlinden AG, van Meurs JB, Rivadeneira F, Pols HA et al. Identifying genetic risk factors for osteoporosis. J Musculoskelet Neuronal Interact 2006;6:16-26.
6. Van Himbergen TM, Van Tits LJH, Roest M, Stalenhoef AFH. The story of PON1: how an organophosphate hydrolyzing enzyme is becoming a player in cardiovascular medicine. Neth J Med 2006;64:34-8.
7. Yilmaz N, Simsek N, Aydin O, Yardan E, Aslan S, Eren E, et al. Decreased paraoxonase 1, arylesterase enzyme activity, and enhanced oxidative stress in patients with mitral and aortic valve insufficiency. Clin Lab 2013;59:597-604.
8. Eren E, Yilmaz N, Aydin O. High density lipoprotein and it's dysfunction. Open Biochem J 2012;6:78-93.
9. Draganov DI, La Du BN. Pharmacogenetics of paraoxonases: a brief review. Naunyn Schmiedebergs Arch Pharmacol 2004;369:78- 88.
10. Yilmaz N, Eren E. Homocysteine oxidative stress and relation to bone mineral density in post-menopausal osteoporosis. Aging Clin Exp Res 2009;21:353-7.
11. Mackinnon ES, El-Sohemy A, Rao AV, Rao LG et al. Paraoxonase 1 polymorphisms 172T/A and 584A/G modify the association between serum concentrations of the antioxidant lycopene and bone turnover markers and oxidative stress parameters in women 25-70 years of age. J Nutrigenet Nutrigenomics 2010;3:1-8.
12. Deakin SP, James RW. Genetic and environmental factors modulating serum concentrations and activities of the antioxidant enzyme paraoxonase-1. Clin Sci (Lond) 2004;107:435-47.
13. Eren Z, Kantarci G, Biyikli N, Arikan H, Tuglular S, Ergen A, Isbir T, Akoglu E et al. Paraoxonase 1 polymorphisms in patients with primary glomerulonephritis: a singlecenter study in Turkey. Iran J Kidney Dis 2012 ;6:181-5.
14. Sztanek F, Seres I, Harangi M, Locsey L, Padra J, Paragh GJ, Asztalos L, Paragh G et al. Decreased paraoxonase 1 (PON1) lactonase activity in hemodialyzed and renal transplanted patients. A novel cardiovascular biomarker in end-stage renal disease. Nephrol Dial Transplant 2012;27:2866-72.
15. Cosman F, de Beur S J, LeBoff M S, Lewiecki EM, Tanner B, Randall S, Lindsay R et al. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int 2014;25: 2359–81.
16. Turgut Cosan D, Colak E, Saydam F, Yazıcı HU, Degirmenci I, Birdane A, Colak E, Gunes HV et al. Association of Paraoxonase 1 (PON1) Gene Polymorphisms and Concentration with Essential Hypertension. Clinical and Experimental Hypertension 2016;38:602-607
17. Tural Ş, Kara N, Alaylı G. Genetics of osteoporosis. Turkish Journal of Osteoporosis. 2011;17:100-9.
18. Ozgen M, Cosan DT, Doganer F, Soyocak A, Armagan O, Gunes HV, Degirmenci I, Ozkara GO, Mutlu FS et al. Relationship between plasminogen activator in hibitor type-1 (PAI 1) gene polymorphisms and osteoporosis in Turkish women. Clinics (Sao Paulo) 2012;67:1299-302.
19. Ozgen M, Cosan DT, Doganer F, Soyocak A, Armagan O,Kuzgun S, Aydogan AM, Gunes HV, Degirmenci I, Mutlu FS et al. Is there any association between osteoporotic vertebral fracture and vitamin K epoxide reductase complex subunit-1 polymorphism in Turkish society? A pilot study. Clinics 2019;74:e739.
20. Yamada Y, Ando F, Niino N, Miki T, Shimokata H et al. Association of polymorphisms of paraoxonase 1 and 2 genes, alone or in combination, with bone mineral density in community-dwelling Japanese. J Hum Genet 2003;48:469-75.
21. Toptaş B, Kurt Ö, Aydoğan HY, Yaylim I, Zeybek Ü, Can A, et al. Investigation of the common paraoxonase 1 variants with paraoxonase activity on bone fragility in Turkish patients. Mol Biol Rep 2013;40:6519- 24.
22. Verit FF, Celik H,Yazgan P,Erel O,Geyikli I et al. Paraoxonase-1 activity as a marker of atherosclerosis is not associated with low bone mineral density in healthy postmenopausal women. Arch Gynecol Obstet. 2007;275:353- 9.
23. Mazière C, Salle V, Gomila C, Mazière JC et al. Oxidized low density lipoprotein enhanced RANKL expression in human osteoblastlike cells. Involvement of ERK, NFkappaB and NFAT. Biochim Biophys Acta 2013;1832:1756-64.
24. Almeida M, Han L, Martin-Millan M, O'Brien CA, Manolagas SC et al. Oxidative stress antagonizes Wnt signaling in osteoblast precursors by diverting beta-catenin from T cell factor- to forkhead box O-mediated transcription. J Biol Chem 2007;282:27298- 305.
25. Xiong J, O'Brien CA. Osteocyte RANKL: new insights into the control of bone remodeling. J Bone Miner Res 2012;27:499-505.
26. Yilmaz N, Kepkep N, Ciçek HK, Celik A, Meram I et al. Relation of parity and homocysteine to bone mineral density of postmenopausal women. Clin Lab 2006;52:49- 56.
27. Eren E, Ellidag HY, Aydin O, Yılmaz N et al. Homocysteine, paraoxonase-1 and vascular endothelial dysfunction: Omnibus viis Romam Pervenitur. J Clin Diagn Res 2014;8:CE01-4.
28. Lobo V, Patil A, Phatak A, Chandra N et al. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn Rev 2010;4:118-26.
29. Almeida M. Aging mechanisms in bone. Bonekey Rep 2012;1. pii: 102. DOI:10.1038/bonekey.2012.102
30. Weitzmann MN, Pacifici R. Estrogen deficiency and bone loss: an inflammatory tale. J Clin Invest 2006;116:1186-94.
31. Lv H, Ma X, Che T, Chen Y et al. Methylation of the promoter A of estrogen receptor alpha gene in hBMSC and osteoblasts and its correlation with homocysteine. Mol Cell Biochem 2011;355:35-45.
32. Yilmaz N. Relationship between paraoxonase and homocysteine: crossroads of oxidative diseases. Arch Med Sci 2012;8:138-53.
33. Mackness B, Mackness MI, Arrol S, Turkie W, Durrington PN et al. Effect of the human serum paraoxonase 55 and 192 genetic polymorphisms on the protection by high density lipoprotein against low density lipoprotein oxidative modification. FEBS Lett 1998;423: 57–60.