Suat ÇAKINA, Selma YÜCEL, Cemre Çağan POLAT

MULTİPLE SKLEROZ HASTALARINDA APOE GEN EKSPRESYONUNUN BELİRLENMESİ

AMAÇ: Apolipoprotein E (ApoE), lipoprotein parçacıklarının reseptör aracılı endositozunda ligand olarak işlev gören bir glikoproteindir. ApoE'nin Alzheimer ve multipl skleroz gibi nörojeneratif hastalıklar ile ilişkisini gösteren çalışmalar vardır. Bu çalışmanın amacı ApoE gen ekspresyonu ile MS arasında bir ilişki olup olmadığını araştırmaktır.GEREÇ VE YÖNTEM: ApoE gen ekspresyonunun multiple skleroz hastlığı üzerinde etkisini saptamak amacıyla yaptığımız çalışmamıza 35 hasta ve 20 sağlıklı birey dahil edilmiştir. ApoE mRNA ekspresyonunun seviyesi, Revers-Transkriptaz Polimeraz Zincir Reaksiyonu (qRT-PCR) ile belirlendi. İstatiksel analiz için SPSS paket programı kullanılarak,t testi, ki-kare testi, Kruskal-Wallis testi ve Mann-Whitney U testi yapıldı ve p <0,05 istatistiksel olarak anlamlı kabul edildi.BULGULAR: Sonuç olarak, ApoE gen ekspresyonunun çoklu skleroz hastalarında ve sağlıklı kişilerin gerçek zamanlı PCR teknikleri kullanılarak karşılaştırılması, gruplar arasında istatistiksel olarak anlamlılık göstermedi (p =0.95).SONUÇ: Çalışmamız ApoE gen ekspresyonunun MS hastalığı ile ilişkili olabileceğini desteklememektedir. ApoE'nin Multipl Skleroz hastalığında rolünü belirlemek için ileri çalışmalara ihtiyaç vardır.

Anahtar Kelimeler:

APOE, multiple sklerozis, gen ekspresyonu

DETERMINATION OF APOE GENE EXPRESSION IN MULTIPLE SCLEROSIS PATIENTS

OBJECTIVE: Apolipoprotein E (ApoE) is a glycoprotein that functions as a ligand in receptor-mediated endocytosis of lipoprotein particles. There are studies showing the association of APOE with neurogenerative diseases such as Alzheimer's disease and multiple sclerosis (MS). The aim of this study was to investigate whether there is a relationship between APOE gene expression and MS.MATERIAL AND METHODS: To determine the effect of APOE gene expression on multiple sclerosis patients, we have included 35 MS patients and 20 healthy subjects into the study. The level of APOE mRNA expression was determined by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). For statistical analysis, t-test, chi-square test, Kruskal-Wallis test and Mann-Whitney U test were performed using SPSS package program and p <0.05 was considered as statistically significant.RESULTS: As a result, the comparison of ApoE gene expression in multiple sclerosis patients and healthy people using real-time PCR technique did not show any statistical significance between the groups (p=0.95).CONCLUSIONS: Our study does not support that ApoE gene expression may be related to MS. Further studies are needed to determine the role of ApoE in Multiple Sclerosis disease.

Keywords:

APOE, multiple sclerosis, Gene expression,

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Pinholt M, Frederiksen JL, Christiansen M. The association between apolipoprotein E and multiple sclerosis. European journal of neurology 2006;13(6):573-80.
Robinson JL, Lee EB, Xie SX, et al. Neurodegenerative disease concomitant proteinopathies are prevalent, age-related and APOE4-associated. Brain : a journal of neurology 2018;141(7):2181-93.
Bekris LM, Galloway NM, Montine TJ, Schellenberg GD, Yu C-E. APOE mRNA and protein expression in postmortem brain are modulated by an extended haplotype structure. Am J Med Genet B Neuropsychiatr Genet. 2010;153B(2):409-17.
Hays CC, Zlatar ZZ, Meloy MJ et al. APOE modifies the interaction of entorhinal cerebral blood flow and cortical thickness on memory function in cognitively normal older adults. NeuroImage 2019;202:116162.
Martinez-Magana JJ, Genis-Mendoza AD, Tovilla-Zarate CA et al. Association between APOE polymorphisms and lipid profile in Mexican Amerindian population. Molecular genetics & genomic medicine 2019:e958.
Santos-Ferreira C, Baptista R, Oliveira-Santos M, Costa R, Pereira Moura J, Gonçalves L. Apolipoprotein E2 Genotype Is Associated with a 2-Fold Increase in the Incidence of Type 2 Diabetes Mellitus: Results from a Long-Term Observational Study. J Lipids. 2019;2019:1698610-.
Li J, Luo J, Liu L, Fu H, Tang L. The genetic association between apolipoprotein E gene polymorphism and Parkinson disease: A meta-Analysis of 47 studies. Medicine 2018;97(43):e12884.
Atageldiyeva KK, Nemr R, Echtay A, Racoubian E, Sarray S, Almawi WY. Apolipoprotein E genetic polymorphism influence the susceptibility to nephropathy in type 2 diabetes patients. Gene 2019;715:144011.
Jairani PS, Aswathy PM, Krishnan D, et al. Apolipoprotein E Polymorphism and Oxidative Stress in Peripheral Blood-Derived Macrophage-Mediated Amyloid-Beta Phagocytosis in Alzheimer's Disease Patients. Cellular and molecular neurobiology 2019;39(3):355-69.
Tang Y, Li YM, Zhang M, Chen YQ, Sun Q. epsilon3/4 genotype of the apolipoprotein E is associated with higher risk of Alzheimer's disease in patients with type 2 diabetes mellitus. Gene. 2019;703:65-70.
Mahley RW, Weisgraber KH, Huang Y. Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America 2006;103(15):5644-51.
Sawcer S, Hellenthal G, Pirinen M, et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 2011;476(7359):214-9.
Schrewe L, Lill CM, Liu T, et al. Investigation of sex-specific effects of apolipoprotein E on severity of EAE and MS. Journal of neuroinflammation 2015;12:234.
Shin S, Walz KA, Archambault AS, et al. Apolipoprotein E mediation of neuro-inflammation in a murine model of multiple sclerosis. Journal of neuroimmunology 2014;271(1-2):8-17.
van der Walt A, Stankovich J, Bahlo M et al. Apolipoprotein genotype does not influence MS severity, cognition, or brain atrophy. Neurology 2009;73(13):1018.
Coon KD, Myers AJ, Craig DW, et al. A high-density whole-genome association study reveals that APOE is the major susceptibility gene for sporadic late-onset Alzheimer's disease. The Journal of clinical psychiatry 2007;68(4):613-8.
Yu CE, Seltman H, Peskind ER, et al. Comprehensive analysis of APOE and selected proximate markers for late-onset Alzheimer's disease: patterns of linkage disequilibrium and disease/marker association. Genomics 2007;89(6):655-65.
Beffert U, Cohn JS, Petit-Turcotte C, et al. Apolipoprotein E and beta-amyloid levels in the hippocampus and frontal cortex of Alzheimer's disease subjects are disease-related and apolipoprotein E genotype dependent. Brain research 1999;843(1-2):87-94.
Bertrand P, Poirier J, Oda T, Finch CE, Pasinetti GM. Association of apolipoprotein E genotype with brain levels of apolipoprotein E and apolipoprotein J (clusterin) in Alzheimer disease. Brain research Molecular brain research 1995;33(1):174-8.
Lambert JC, Araria-Goumidi L, Myllykangas L, et al. Contribution of APOE promoter polymorphisms to Alzheimer's disease risk. Neurology 2002;59(1):59-66.
Matsui T, Ingelsson M, Fukumoto H, et al. Expression of APP pathway mRNAs and proteins in Alzheimer's disease. Brain research. 2007;1161:116-23.
Yamagata K, Urakami K, Ikeda K, et al. High expression of apolipoprotein E mRNA in the brains with sporadic Alzheimer's disease. Dementia and geriatric cognitive disorders 2001;12(2):57-62.
Sena A, Couderc R, Ferret-Sena V, et al. Apolipoprotein E polymorphism interacts with cigarette smoking in progression of multiple sclerosis. European journal of neurology 2009;16(7):832-7.
Sena A, Macedo A, Ferret-Sena V, Capela C, Pedrosa R. Serum Lipoprotein Profile Is Associated With Protective Effects of Oral Contraceptive Use on Multiple Sclerosis Severity: A Cross-Sectional Study. Frontiers in neurology 2019;10:60.
Pirttila T, Haanpaa M, Mehta PD, Lehtimaki T. Apolipoprotein E (APOE) phenotype and APOE concentrations in multiple sclerosis and acute herpes zoster. Acta neurologica Scandinavica 2000;102(2):94-8.
Gaillard O, Gervais A, Meillet D, Delattre J, Lyon-Caen O, Schuller E. Apolipoprotein E intrathecal synthesis is decreased in multiple sclerosis patients. Annals of clinical biochemistry 1996;33 ( Pt 2):148-50.