Yıl 2018, Cilt 15 , Sayı 3, Sayfalar 176 - 181 2018-12-12

The Association Between Blood Homocystein-Paraoxonase Levels and the Polymorphisms of Methylenetetrahydrofolate Reductase and Paraoxonase 1 Genes in Alzheimer Disease Patients
ALZHEİMER HASTALARINDA SERUM HOMOSİSTEİN VE PARAOKSONAZ SEVİYELERİ İLE MTHFR VE PON 1 GEN POLİMORFİZMİNİN KLİNİK İLE KORELASYONU

Hasan BAYINDIR [1] , Gülay GÜLEÇ CEYLAN [2] , Salim NEŞELİOĞLU [3]


Background: The aim of this study is to detect serum homocysteine increase (Hcy) and paraoxonase decrease together with methylenetetrahydrofolate reductase (MTHFR) and paraoxonase 1 (PON1) gene polymorphisms in Alzheimer's patients and to evaluate the correlation with clinic in these patients.

Material and Methods: In our study; total 103 individuals were included and 51 of them had Alzheimer's disease (AD) diagnosis clinically according to DSM-IV criteria and 52 of them did not have AD. In patient and control group; Hcy levels and paraoxonase activity, MTHFR C677T – A1298C and PON1 L55M - Q192R gene polymorphisms were investigated.

Results: Average age of the patients in our study was found as 73.67±7.91 years. In patient group; Hcy level was significantly high (p:0,024) and paraoxonase activity was found low in patient group (p:0,047). In patients with MTHFR C677T and A1298C polymorphism, Hcy levels were high but there was no significant difference between groups (p>0,05). In PON1 L55M polymorphism PON levels were low (p<0,009). In patients with Q192R polymorphism PON levels were significantly high especially in heterozygote group (p:0,024).

Conclusion: It was seen that Hcy levels were high and PON activity was low in Alzheimer's disease. MTHFR C677T and A1298C polymorphism could not be associated with AD but it was observed that the polymorphism could increase Hcy levels. As a result; PON 1 L55M polymorphism was thought to be a risk factor in AD and on the other hand Q192R polymorphism was thought to be a protective factor.


Amaç: Bu çalışmanın amacı Alzheimer hastalarında, serum homosistein (Hcy) yüksekliği ve paraoksonaz düşüklüğü ile metilentetrahidrofolat redüktaz (MTHFR) ve paraoksonaz 1 (PON1) gen polimorfizmlerinin tespit edilmesi, bu hastalarda klinik ile korelasyonunun değerlendirilmesidir.

Materyal ve metod: Çalışmaya klinik olarak Alzheimer hastalığı (AH) tanısı DSM-IV kriterlerine göre konulan 51 hasta ve AH olmayan 52 kişi olmak üzere toplam 103 olgu alındı.  Hasta ve kontrol grubunda, Hcy düzeyleri ve paraoksonaz aktiviteleri, MTHFR C677T – A1298C ve PON1 L55M - Q192R gen polimorfizmleri incelendi.

Bulgular: Çalışmamızda hastaların yaş ortalaması 73.67±7.91 yıl olarak bulundu. Hasta grupta Hcy düzeyi anlamlı olarak yüksek iken (p:0,024), paraoksonaz aktivitesi hasta grupta düşük olarak bulundu (p:0,047). MTHFR C677T ve A1298C polimorfizmi olanlarda Hcy seviyeleri yüksekti ancak gruplar arasında anlamlı bir fark yoktu (p>0,05). PON1 L55M polimorfizminde PON düzeyleri düşüktü (p<0,009). Q192R polimorfizmi olanlarda PON düzeyi heterezigot grupta daha belirgin olmak üzere yüksekti (p:0,024).

Sonuç: Alzheimer hastalığında Hcy düzeylerinde yükseklik ve PON aktivitesinde düşüklük olduğu görüldü. MTHFR C677T ve A1298C polimorfizmi AH ile ilişkili bulunmadı, ancak Hcy düzeylerini arttırdığı gözlendi. PON 1 L55M polimorfizmi AH da risk faktörü, Q192R polimorfizminin ise koruyucu faktör olabileceği sonucuna varıldı.

  • REFERENCES1- Shobab LA, Hsiung GY, Feldman HH. Cholesterol in Alzheimer's disease. Lancet Neurol 2005; 4: 841-52.2- Yamada M, Sasaki H, Mimori Y, Kasagi F. Prevalence and risks of dementia in the Japanese population: RERF's adult health study Hiroshima subjects. Radiation Effects Research Foundation. J Am Geriatr Soc. 1999;47:189-95.3- Jara-Prado A, Ortega-Vazguez A, Martinez –Ruano L, Rios C, Santamaria A. Homocysteine-induced brain lipd peroxidation: effect of NMDA receptor blockade, antioxidant treatment, and nitric oxide synthase inhibition. Neuroyox Res 2003; 5:237-2434- Lustbader JW et al. ABAD directly links Abeta to mitochondrial toxicity in Alzheimer’s disease. Science 2004; 304:448-452.5- Dorszewska J, Florezak J, Rozycka A, Kempisty B,Oxidative DNA damage and level of thiols as related to polymorphisms of MTHFR, MTR, MTHFD1 in Alzheimer’s and Parkinson’s diseases. Acta Neurobiol Exp 2007,67:113-1296- Fodinger M, Horl WH, Sunder-Plassman G. Molecular biology of 5,10- methylenetetrahydrofolate reductase. J Nephrol, 2000;13:20-33.7- Otocka A, Orlowska M, The role of genetic (PON1 polymorphism) and environmental factors, especially physical activity, in antioxidant function of paraoxonase. Postepy Hig Med Dosw. 2009; 63: 668-6778- Kelada S N, Costa-Mallen P, Checkoway H, Viernes H A, Farin F M, Smith-Weller T, Franklin G M, Costa L G. Paraoxonase 1 promoter and coding region polymorphisms in Parkinson’s disease. J Neurol Neurosurg Psychiatry 2003;74:545–5489- Yue Zhang M, Miao L, Sheng Li Y, Yuan Hu G. Meta-analysis of the methylene tetra hydrofolate reductase C677T polymorphism and susceptibility to Alzheimer’s disease. Neuroscience Research. 2010;68, 142–150.10- Van Oijen M, Arp P.P, De Jong F.J, Hofmann A,Koudstaal P.J, Uitterlinden A.G, Breteler M.M. Polymorphisms in the interleukin 6 and transforming growth factor beta 1 gene and risk of dementia. The Rotterdam Study Neurescience Lett. 2006;402,113-117.11- Beilby J, Rossi E. Number 58: homocysteine and disease. Pathology. 2000;32,262-273. 12- Kumar J, Das S.K, Sharma P, Karthikeyan G, Ramakrishman L, Sengrupta S. Homoccysteine levels are associated with MTHFR A1298 polymorphism in indian population. J. Hum. Genet. 2005;50,655-663.13- Dufouil C, Alperovitch A, Ducros V, Tzourio C. Homocysteine white matter hyperintensities and cognition in healthy elderly people. Ann. Neurol.2003;53,214-221.14- Zhang Y.D, Ke X.Y, Shen W, Liu Y. Relationship of homocysteine and gene polymorphisms of its related metabolic enzymes with Alzheimer’s disease. Chin. Med. Sci.2005;20,247-251.15- Mansoori N, Tripathi M, Luthra K, Alam R, Lakshmy R, Sharma S, Arulselvi S, Parveen S, Mukhopadhyay AK. MTHFR (677 and 1298) and IL-6-174 G/C genes in pathogenesis of Alzheimer’s and vascular dementia and their epistatic interaction. Neurobiol Aging. 2012;33:1003.e1-816- Mansouri L, Fekih-Mrissa N, Klai S, Mansour M, Gritli N, Mrissa R. Association of methylenetetrahydrofolate reductase polymorphisms with susceptibility to Alzheimer’s disease. Clinical Neurology and Neurosurgery, 2013;115, 1693– 169617- Dantoine T.F, Drouet M, Debord J, Merle L, Cogne M, Charmes J.P. Paraoxonase 1 192/55 gene polymorphisms in Alzheimer’s disease. Ann. N.Y. Acad. Sci. 2002; 977, 239–244.18- Paragh G, Balla P, Katona E, Seres I, Egerházi A, Degrell I. Serum paraoxonase activity changes in patients with Alzheimer’s disease and vascular dementia. Eur. Arch. Psychiatry Clin. Neurosci. 2002;252, 63–67.19- Leduc V, Théroux L, Dea D, Robitaille Y, Poirier J. Involvement of paraoxonase 1 genetic variants in Alzheimer's disease neuropathology. Eur J Neurosci. 2009;30:1823-30.20- He XM, Zhang ZX, Zhang JW, Zhou YT, Tang MN, Wu CB, Hong Z. Paraoxonase 1 gene Gln192Arg polymorphism in and Alzheimer disease. Zhonghua Nei Ke Za Zhi. 2006;45:270-3
Birincil Dil en
Bölüm Araştırma Makalesi
Yazarlar

Orcid: 0000-0002-9260-2230
Yazar: Hasan BAYINDIR (Sorumlu Yazar)
Kurum: DEPARTMENT OF NEUROLOGY
Ülke: Turkey


Orcid: 0000-0000-9735-2015
Yazar: Gülay GÜLEÇ CEYLAN
Kurum: DEPARTMENT OF MEDICAL GENETICS
Ülke: Turkey


Orcid: 0000-0002-0974-5717
Yazar: Salim NEŞELİOĞLU
Kurum: DEPARTMENT OF MEDICAL BIOCHEMISTRY
Ülke: Turkey


Tarihler

Yayımlanma Tarihi : 12 Aralık 2018

Bibtex @tez Özeti { hutfd461326, journal = {Harran Üniversitesi Tıp Fakültesi Dergisi}, issn = {1304-9623}, eissn = {1309-4025}, address = {tipdergisi@harran.edu.tr}, publisher = {Harran Üniversitesi}, year = {2018}, volume = {15}, pages = {176 - 181}, doi = {}, title = {The Association Between Blood Homocystein-Paraoxonase Levels and the Polymorphisms of Methylenetetrahydrofolate Reductase and Paraoxonase 1 Genes in Alzheimer Disease Patients}, key = {cite}, author = {Bayındır, Hasan and Güleç Ceylan, Gülay and Neşeli̇oğlu, Salim} }
APA Bayındır, H , Güleç Ceylan, G , Neşeli̇oğlu, S . (2018). The Association Between Blood Homocystein-Paraoxonase Levels and the Polymorphisms of Methylenetetrahydrofolate Reductase and Paraoxonase 1 Genes in Alzheimer Disease Patients . Harran Üniversitesi Tıp Fakültesi Dergisi , 15 (3) , 176-181 . Retrieved from https://dergipark.org.tr/tr/pub/hutfd/issue/41021/461326
MLA Bayındır, H , Güleç Ceylan, G , Neşeli̇oğlu, S . "The Association Between Blood Homocystein-Paraoxonase Levels and the Polymorphisms of Methylenetetrahydrofolate Reductase and Paraoxonase 1 Genes in Alzheimer Disease Patients" . Harran Üniversitesi Tıp Fakültesi Dergisi 15 (2018 ): 176-181 <https://dergipark.org.tr/tr/pub/hutfd/issue/41021/461326>
Chicago Bayındır, H , Güleç Ceylan, G , Neşeli̇oğlu, S . "The Association Between Blood Homocystein-Paraoxonase Levels and the Polymorphisms of Methylenetetrahydrofolate Reductase and Paraoxonase 1 Genes in Alzheimer Disease Patients". Harran Üniversitesi Tıp Fakültesi Dergisi 15 (2018 ): 176-181
RIS TY - JOUR T1 - The Association Between Blood Homocystein-Paraoxonase Levels and the Polymorphisms of Methylenetetrahydrofolate Reductase and Paraoxonase 1 Genes in Alzheimer Disease Patients AU - Hasan Bayındır , Gülay Güleç Ceylan , Salim Neşeli̇oğlu Y1 - 2018 PY - 2018 N1 - DO - T2 - Harran Üniversitesi Tıp Fakültesi Dergisi JF - Journal JO - JOR SP - 176 EP - 181 VL - 15 IS - 3 SN - 1304-9623-1309-4025 M3 - UR - Y2 - 2018 ER -
EndNote %0 Harran Üniversitesi Tıp Fakültesi Dergisi The Association Between Blood Homocystein-Paraoxonase Levels and the Polymorphisms of Methylenetetrahydrofolate Reductase and Paraoxonase 1 Genes in Alzheimer Disease Patients %A Hasan Bayındır , Gülay Güleç Ceylan , Salim Neşeli̇oğlu %T The Association Between Blood Homocystein-Paraoxonase Levels and the Polymorphisms of Methylenetetrahydrofolate Reductase and Paraoxonase 1 Genes in Alzheimer Disease Patients %D 2018 %J Harran Üniversitesi Tıp Fakültesi Dergisi %P 1304-9623-1309-4025 %V 15 %N 3 %R %U
ISNAD Bayındır, Hasan , Güleç Ceylan, Gülay , Neşeli̇oğlu, Salim . "The Association Between Blood Homocystein-Paraoxonase Levels and the Polymorphisms of Methylenetetrahydrofolate Reductase and Paraoxonase 1 Genes in Alzheimer Disease Patients". Harran Üniversitesi Tıp Fakültesi Dergisi 15 / 3 (Aralık 2018): 176-181 .
AMA Bayındır H , Güleç Ceylan G , Neşeli̇oğlu S . The Association Between Blood Homocystein-Paraoxonase Levels and the Polymorphisms of Methylenetetrahydrofolate Reductase and Paraoxonase 1 Genes in Alzheimer Disease Patients. Harran Üniversitesi Tıp Fakültesi Dergisi. 2018; 15(3): 176-181.
Vancouver Bayındır H , Güleç Ceylan G , Neşeli̇oğlu S . The Association Between Blood Homocystein-Paraoxonase Levels and the Polymorphisms of Methylenetetrahydrofolate Reductase and Paraoxonase 1 Genes in Alzheimer Disease Patients. Harran Üniversitesi Tıp Fakültesi Dergisi. 2018; 15(3): 176-181.
IEEE H. Bayındır , G. Güleç Ceylan ve S. Neşeli̇oğlu , "The Association Between Blood Homocystein-Paraoxonase Levels and the Polymorphisms of Methylenetetrahydrofolate Reductase and Paraoxonase 1 Genes in Alzheimer Disease Patients", Harran Üniversitesi Tıp Fakültesi Dergisi, c. 15, sayı. 3, ss. 176-181, Ara. 2018