Abstract
Multiple sclerosis (MS) is a multifactorial disease of the central nervous system. The apolipoprotein E (APOE) and interleukin 1 β (IL1B) genes are considered to be candidate genes of MS. The aim of the study was to examine the hypothesis of the importance of APOE and IL1B gene polymorphisms in MS development in ethnic Tatars. DNA samples isolated by phenol-chloroform extraction from peripheral blood of 383 ethnic Tatars (120 MS patients and 263 healthy donors) were studied. 112C/R and 158R/C APOE gene polymorphisms as well as −511T/C IL1B gene polymorphism were analyzed by polymerase chain reaction (PCR) followed by PCR product digestion by endonuclease. Odds ratio (OR) values were used for evaluation of the relative risk of alleles and(or) genotype combinations. It has been shown that APOE*2/*3 genotype is associated with low risk of the disease development (OR = 0.20) in women. A combined effect of APOE and IL1B allelic variants has been discovered indicating the increased risk of the disease development in the carriers of APOE*4 and IL1B*T/*T alleles (OR = 4.76).
Similar content being viewed by others
References
Gusev, E.I., Boiko, A.N., Zavalishin, I.A., and Bykova, O.V., Contemporary Epidemiology of Multiple Sclerosis, in Rasseyannyi skleroz i drugie demieliniziruyushchie zabolevaniya (Multiple Sclerosis and Other Demyelinating Disorders), Moscow: Miklosh, 2004, pp. 8–29.
Bakhtiyarova, K.Z. and Magzhanov, R.V., Epidemiology of Multiple Sclerosis in the Republic of Bashkortostan, in Organizatsiya pomoshchi bol’nym rasseyannym sklerozom (Arrangement of Caring for Patients with Multiple Sclerosis), Proc. Workshop, Tomsk, 2003, pp. 3–5.
Kulakova, O.G., Boiko, A.N., and Favorova, O.O., Cytokine Role in the Pathogeneses of Multiple Sclerosis, in Rasseyannyi skleroz i drugie demieliniziruyushchie zabolevaniya (Multiple Sclerosis and Other Demyelinating Disorders), Moscow: Miklosh, 2004, pp. 75–92.
Zavalishin, I.A., Zakharova, M.N., Zhuchenko, T.D., and Peresedova, A.V., Etiology and Pathogeneses of Multiple Sclerosis, in Rasseyannyi skleroz: Izbrannye voprosy teorii i praktiki (Multiple Sclerosis: Selected Issues in Theory and Practice), Moscow: Res. Inst. Nevrologii RAMN, 2000, pp. 537–579.
Ebers, G.C., Bulman, D.E., Sadovnick, A.D., et al., A Population-Based Study of Multiple Sclerosis in Twins, New England J. Med., 1986, vol. 315, pp. 1638–1642.
Compston, A. and Sadovnick, A.D., Epidemiology and Genetics of Multiple Sclerosis, Curr. Opin. Neurol. Neurosurg., 1992, vol. 5, pp. 175–181.
Dyment, D.A., Ebers, G.C., and Sadovnick, A.D., Genetics of Multiple Sclerosis, Lancet Neurol., 2004, vol. 3, pp. 104–110.
Graham, D.I., Horsburgh, K., Nicoll, J., et al., Apolipoprotein E and the Response of the Brain to Injury, Acta. Neurochir., 1999, vol. 73(suppl.), pp. 89–92.
Han, X., The Role of Apolipoprotein E in Lipid Metabolism in the Central Nervous System, Cell Mol. Life Sci., 2004, vol. 61, pp. 1896–1906.
Weisgraber, K., Innerarity, T., and Mahley, R., Abnormal Lipoprotein Receptor-Binding Activity of the Human apoE Apoprotein Due to Cysteine-Arginine Interchange at a Single Site, J. Biol. Chem., 1989, vol. 257, pp. 2518–2521.
Moynagh, P.N., The Interleukin-1 Signalling Pathway in Astrocytes: A Key Contributor to Inflammation in the Brain, J. Anat., 2005, vol. 207, pp. 265–269.
Moos, V., Rudwaleit, M., Herzog, V., et al., Association of Genotypes Affecting the Expression of Interleukin-1beta or Interleukin-1 Receptor Antagonist with Osteoarthritis, Arthritis Rheum., 2000, vol. 43, pp. 2417–2422.
Pociot, F., Molvig, J., Wogensen, L., et al., TaqI Polymorphism in the Human Interleukin-1 (IL-1) Gene Correlates with IL-1 Secretion in Vitro, Eur. J. Clin. Invest., 1992, vol. 22, pp. 396–402.
McDonald, W., Compston, A., Edan, G., et al., Recommended Diagnostic Criteria for Multiple Sclerosis: Guidelines from the International Panel on the Diagnosis of Multiple Sclerosis, Ann. Neurol., 2001, vol. 50, pp. 121–127.
Hixson, J.E. and Vernier, D.T., Restriction Isotyping of Human Apolipoprotein E by Gene Amplification and Cleavage with HhaI, J. Lipid Res., 1990, vol. 31, pp. 545–548.
Kato, S., Onda, M., Yamada, S., et al., Association of the Interleukin-1 Genetic Polymorphism and Gastric Cancer Risk in Japanese, J. Gastroenterol., 2001, vol. 36, pp. 696–699.
Roff, P. and Bentzen, P., The Statistical Analysis of DNA Polymorphism Chi 2 and Problem of Small Samples, Mol. Biol. Evol., 1989, vol. 6, pp. 539–545.
Zhivotovsky, L.A., Populyatsionnaya biometriya (Population Biometry), Moscow: Nauka, 1991.
Bland, J.M. and Altman, D.G., The Odds Ratio, Brit. Med. J., 2000, vol. 320, p. 1468.
Poirier, J., Apolipoprotein E in Animal Models of CNS Injury and in Alzheimer’s Disease, Trends Neurosci., 1994, vol. 17, pp. 525–530.
Han, X., Cheng, H., Fryer, J., et al., Novel Role for Apolipoprotein E in the Central Nervous System: Modulation of Sulfatide Content, J. Biol. Chem., 2003, vol. 278, pp. 8043–8051.
Gailard, O., Gervais, A., Meillet, D., et al., Apolipoprotein E and Multiple Sclerosis: A Biochemical and Genetic Investigation, J. Neurol. Sci., 1998, vol. 158, pp. 180–186.
Laskowitz, D.T., Lee, D.M., Schmechel, D., and Staats, H.F., Altered Immune Responses in Apolipoprotein E-Deficient Mice, J. Lipid Res., 2000, vol. 41, p. 613.
Nathan, B.P., Bellosta, S., Sanan, D.A., et al., Differential Effects of Apolipoprotein E3 and E4 on Neuronal Growth in Vitro, Science, 1994, vol. 264, pp. 850–852.
Pedersen, W.A., Chan, S.L., and Mattson, M.P., A Mechanism for the Neuroprotective Effect of Apolipoprotein E: Isoform-Specific Modification by the Lipid Peroxidation Product 4-Hydroxynonenal, J. Neurochem., 2000, vol. 74, pp. 1426–1433.
Hashimoto, Y., Jiang, H., Niikura, T., et al., Neuronal Apoptosis by Apolipoprotein E4 Through Low-Density Lipoprotein Receptor-Related Protein and Heterotrimeric GTPases, J. Neurosci., 2000, vol. 20, pp. 8401–8409.
Buttini, M., Orth, M., Bellosta, S., et al., Expression of Human Apolipoprotein E3 or E4 in the Brains of Apoe-/-Mice: Isoform-Specific Effects on Neurodegeneration, J. Neurosci., 1999, vol. 19, pp. 4867–4880.
DeKroon, R., Mihovilovic, M., Goodger, Z., et al., ApoE Genotype-Specific Inhibition of Apoptosis, J. Lipid Res., 2003, vol. 44, pp. 1566–1573.
Arendt, T., Schindler, C., Bruckner, M.K., et al., Plastic Neuronal Remodeling Is Impaired in Patients with Alzheimer’s Disease Carrying Apolipoprotein e4 Allele, J. Neurosci., 1997, vol. 17, pp. 516–529.
Roses, A.D. and Saunders, A., Head Injury, Amyloid Beta and Alzheimer’s Disease, Nat. Med., 1995, vol. 1, pp. 603–604.
Schmidt, S., Barcellos, L.F., DeSombre, K., et al., Association of Polymorphisms in the Apolipoprotein E Region with Susceptibility to and Progression of Multiple Sclerosis, Am. J. Hum. Genet., 2002, vol. 70, pp. 708–717.
Evangelou, N., Jackson, M., Beeson, D., and Palace, J., Association of the APOE e4 Allele with Disease Activity in Multiple Sclerosis, J. Neurol. Neurosurg. Psychiatry, 1999, vol. 67, pp. 203–205.
Kantarci, O.H., Hebrink, D.D., Achenbach, S.J., et al., Association of APOE Polymorphisms with Disease Severity in MS Is Limited to Women, Neurology, 2004, vol. 62, pp. 811–814.
Raber, J., Bongers, G., LeFevour, A., et al., Androgens Protect against Apolipoprotein E4-Induced Cognitive Deficits, J. Neurosci., 2002, vol. 22, pp. 5204–5209.
Zofkova, I., Zajckova, K., Hill, M., and Horinekl, A., Apolipoprotein E Gene Determines Serum Testosterone and Dehydroepiandrosterone Levels in Postmenopausal Women, Eur. J. Endocrinol., 2002, vol. 147, pp. 503–506.
Lahita, R.G., Gender and the Immune System, J. Gend. Specif. Med., 2000, vol. 3, pp. 19–22.
Weatherby, S., Mann, C., Fryer, A., et al., No Association between the APOE e4 Allele and Outcome and Susceptibility in Primary Progressive Multiple Sclerosis, J. Neurol. Neurosurg. Psychiatry, 2000, vol. 68, pp. 532–541.
Sedano, M., Calmarza, P., Perez, L., and Trejo, J., No Association of Apolipoprotein E4 Genotype with Faster Progression or Less Recovery of Relapses in a Spanish Cohort of Multiple Sclerosis, Mult. Scler., 2006, vol. 12, pp. 13–18.
Burwick, R., Ramsay, P., Haines, J., et al., APOE Epsilon Variation in Multiple Sclerosis Susceptibility and Disease Severity: Some Answers, Neurology, 2006, vol. 66, pp. 1373–1383.
Moynagh, P., The Interleukin-1 Signaling Pathway in Astrocytes: A Key Contributor to Inflammation in the Brain, J. Anat., 2005, vol. 207, pp. 265–269.
Bidwell, J., Keen, L., Gallagher, G., et al., Cytokine Gene Polymorphism in Human Disease: On-Line Data-bases, Supplement 1, Genes Immunity, 2001, vol. 2, pp. 61–70.
Laurincova, B., Interleukin-1 Family: From Genes to Human Disease, Acta Univ. Palacki Olomuc Fac. Med., 2000, vol. 143, pp. 19–29.
Ferri, C., Sciacca, F., and Grimaldi, L., Lack of Association between IL-1α and IL-1β Promoter Polymorphisms and Multiple Sclerosis, J. Neurol. Neurosurg. Psychiatry, 2003, vol. 69, pp. 564–565.
Hooper-van Veen, T., Schrijver, H., Zwiers, A., et al., The Interleukin-1 Gene Family in Multiple Sclerosis Susceptibility and Disease Course, Mult. Scler., 2003, vol. 9, pp. 535–539.
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © O.E. Mustafina, K.Z. Bakhtijarova, A.M. Mikhailova, I.A. Tuktarova, A.N. Khusainova, T.R. Nasibullin, R.V. Magjanov, 2008, published in Genetika, 2008, Vol. 44, No. 3, pp. 407–413.
Rights and permissions
About this article
Cite this article
Mustafina, O.E., Bakhtijarova, K.Z., Mikhailova, A.M. et al. Analysis of the association of allelic variants of apolypoprotein E and interleukin 1 beta genes with multiple sclerosis in ethnic Tatars. Russ J Genet 44, 350–356 (2008). https://doi.org/10.1134/S1022795408030174
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1022795408030174