ALZHEİMER HASTALARINDA SERUM HOMOSİSTEİN VE PARAOKSONAZ SEVİYELERİ İLE MTHFR VE PON 1 GEN POLİMORFİZMİNİN KLİNİK İLE KORELASYONU

Yıl 2018, Cilt: 15 Sayı: 3, 176 - 181, 12.12.2018

Hasan Bayındır , Gülay Güleç Ceylan Salim Neşelioğlu

Öz

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.

Anahtar Kelimeler

Alzheimer hastalığı, homosistein, metilentetrahidrofolat redüktaz, paraoksonaz gen polimorfizmi

The Association Between Blood Homocystein-Paraoxonase Levels and the Polymorphisms of Methylenetetrahydrofolate Reductase and Paraoxonase 1 Genes in Alzheimer Disease Patients

Öz

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.

Anahtar Kelimeler

Alzheimer's disease, homocysteine, methylenetetrahydrofolate reductase, paraoxonase gene polymorphism

Kaynakça

• 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