Araştırma Makalesi
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Association Between Tumor Necrosis Factor Alpha Gene Polymorphism (-376) and Multiple Sclerosis in Turkish Population

Yıl 2018, Cilt: 30 Sayı: 1, 50 - 54, 09.04.2018
https://doi.org/10.7240/marufbd.289591

Öz

The
purpose of this study is the detection of the association between MS and TNF-A
gene promoter -376 polymorphism.In this study, 100 MS patients and 100 healthy
controls were examined. Firstly, genomic DNA was extracted from human leukocyte
nuclei isolated from whole blood by standard methods and then the promoter
region of TNF-A including -376 polymorphism was amplified with PCR method.
Secondly, the PCR products were digested with a digestion enzyme and genotype
distributions and allele frequencies were determined. A strong association
between MS and TNF-A -376 genotype distribution was detected        (p= 0,010). At the same time TNF-A -376
allele frequency was showed an association with MS (p=0,011), but this
association indicates that GA genotype and A allele have protective effects.
There is not an association between TNF-A -376 polymorphism and MS progression,
but GA genotype and A allele may be the protective factors in the healthy people.

Kaynakça

  • Noseworthy JH., Lucchinetti C. ve Rodriguez M., Weinshenker BG. (2000). Multiple sclerosis. N Engl J Med., 343, 938-952.
  • Dyment DA., Sadovnick AD. ve Ebers GC. (1997). Genetics of multiple sclerosis. Hum Mol Genet, 6, 1693-1698.
  • Elahi MM., Asotra K., Matata BM. ve Mastana SS. (2009). Tumor necrosis factor alpha -308 gene locus promoter polymorphism: an analysis of association with health and disease. Biochim Biophys Acta, 1792, 163-172.
  • Zipp, F., Weber, F., Huber, S., Sotgiu, S., Czlonkowska, A., Holler, E., Albert, E., Weiss, E. H., Wekerle, H., ve Hohlfeld, R. (1995). Genetic control of multiple sclerosis: increased production of lymphotoxin and tumor necrosis factor-alpha by HLA-DR2+ T cells. Ann Neurol, 38, 723-730.
  • Hurwitz BJ. (2009).The diagnosis of multiple sclerosis and the clinical subtypes. Ann Indian Acad Neurol, 12, 226-230.
  • Kassiotis G. ve Kollias G. (2001). TNF and receptors in organ-specific autoimmune disease: multi-layered functioning mirrored in animal models. J Clin Invest, 107, 1507-1508.
  • Sharief MK.ve Hentges R. (1991). Association between tumor necrosis factor-alpha and disease progression in patients with multiple sclerosis. N Engl J Med, 325, 467-472.
  • Fargion S., Valenti L., Dongiovanni P. ve Fracanzani AL. (2004). TNFalpha promoter polymorphisms. Methods Mol Med, 98, 47-58.
  • Braun, N., Michel, U., Ernst, B. P., Metzner, R., Bitsch, A., Weber, F., ve Rieckmann, P. (1996). Gene polymorphism at position -308 of the tumor-necrosis-factor-alpha (TNF-alpha) in multiple sclerosis and it's influence on the regulation of TNF-alpha production. Neurosci Lett, 215(2), 75-78.
  • Hauser, S. L. (1995). Tumor necrosis factor: immunogenetics and disease. Ann Neurol, 38(5), 702-704.
  • Weinshenker, B. G., Wingerchuk, D. M., Liu, Q., Bissonet, A. S., Schaid, D. J., ve Sommer, S. S. (1997). Genetic variation in the tumor necrosis factor alpha gene and the outcome of multiple sclerosis. Neurology, 49(2), 378-385.
  • Wingerchuk, D., Liu, Q., Sobell, J., Sommer, S., ve Weinshenker, B. G. (1997). A population-based case-control study of the tumor necrosis factor alpha-308 polymorphism in multiple sclerosis. Neurology, 49(2), 626-628.
  • Bayley, J. P., de Rooij, H., van den Elsen, P. J., Huizinga, T. W., ve Verweij, C. L. (2001). Functional analysis of linker-scan mutants spanning the -376, -308, -244, and -238 polymorphic sites of the TNF-alpha promoter. Cytokine, 14(6), 316-323.
  • de Jong, B. A., Huizinga, T. W., Zanelli, E., Giphart, M. J., Bollen, E. L., Uitdehaag, B. M., Polman, C. H., ve Westendorp, R. G. (2002). Evidence for additional genetic risk indicators of relapse-onset MS within the HLA region. Neurology, 59(4), 549-555.
  • Wirz, S. A., Morale, M. C., Marchetti, B., Barr, A. M., Sotgiu, S., Rosati, G., Pugliatti, M., Sanna, M. V., Giliberto, O., Bartfai, T., ve Conti, B. (2004). High frequency of TNF alleles -238A and -376A in individuals from northern Sardinia. Cytokine, 26(4), 149-154.
  • Fernandez-Arquero, M., Arroyo, R., Rubio, A., Martin, C., Vigil, P., Conejero, L., Figueredo, M. A., ve de la Concha, E. G. (1999). Primary association of a TNF gene polymorphism with susceptibility to multiple sclerosis. Neurology, 53(6), 1361-1363.
  • Losonczi, E., Bencsik, K., Nagy, Z. F., Honti, V., Szalczer, E., Rajda, C., Illes, Z., Matyas, K., Rozsa, C., Csepany, T., Fuvesi, J., ve Vecsei, L. (2009). Tumour necrosis factor alpha gene (TNF-alpha) -376 polymorphism in Hungarian patients with primary progressive multiple sclerosis. J Neuroimmunol, 208(1-2), 115-118.
  • Drulovic, J., Popadic, D., Mesaros, S., Dujmovic, I., Cvetkovic, I., Miljkovic, D., Stojsavljevic, N., Pravica, V., Pekmezovic, T., Bogdanovic, G., Jarebinski, M., ve Mostarica Stojkovic, M. (2003). Decreased frequency of the tumor necrosis factor alpha -308 allele in Serbian patients with multiple sclerosis. Eur Neurol, 50(1), 25-29.
  • He, B., Navikas, V., Lundahl, J., Soderstrom, M., ve Hillert, J. (1995). Tumor necrosis factor alpha-308 alleles in multiple sclerosis and optic neuritis. J Neuroimmunol, 63(2), 143-147.
  • Huizinga, T. W., Westendorp, R. G., Bollen, E. L., Keijsers, V., Brinkman, B. M., Langermans, J. A., Breedveld, F. C., Verweij, C. L., van de Gaer, L., Dams, L., Crusius, J. B., Garcia-Gonzalez, A., van Oosten, B. W., Polman, C. H., ve Pena, A. S. (1997). TNF-alpha promoter polymorphisms, production and susceptibility to multiple sclerosis in different groups of patients. J Neuroimmunol, 72(2), 149-153.
  • Ristic, S., Lovrecic, L., Starcevic-Cizmarevic, N., Brajenovic-Milic, B., Sega Jazbec, S., Sepcic, J., Kapovic, M., ve Peterlin, B. (2007). Tumor necrosis factor-alpha-308 gene polymorphism in Croatian and Slovenian multiple sclerosis patients. Eur Neurol, 57(4), 203-207.
  • Maurer, M., Kruse, N., Giess, R., Kyriallis, K., Toyka, K. V., & Rieckmann, P. (1999). Gene polymorphism at position -308 of the tumor necrosis factor alpha promotor is not associated with disease progression in multiple sclerosis patients. J Neurol, 246(10), 949-954.
  • Lassmann, H., Bruck, W., ve Lucchinetti, C. F. (2007). The immunopathology of multiple sclerosis: an overview. Brain Pathol, 17(2), 210-218.
  • Knight, J. C., Udalova, I., Hill, A. V., Greenwood, B. M., Peshu, N., Marsh, K., ve Kwiatkowski, D. (1999). A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria. Nat Genet, 22(2), 145-150.

Türk Popülasyonu’nda Tümor Nekroz Faktör Alfa Gen Polimorfizmi (-376) ile Multipl Skleroz Arasındaki İlişki

Yıl 2018, Cilt: 30 Sayı: 1, 50 - 54, 09.04.2018
https://doi.org/10.7240/marufbd.289591

Öz

Bu araştırmanın amacı Multipl Skleroz (MS) ile Tümor Nekroz Faktör-Alfa (TNF-A) geninin
promotör bölgesindeki (-376) gen polimorfizmi arasındaki ilişkininin ortaya
çıkarılmasıdır. Yapılan çalışmada 100 MS hastası ve 100 sağlıklı kontrol olmak
üzere toplam 200 birey incelenmiştir. Bunun için ilk olarak kandan DNA
izolasyonu yapılmış ve elde edilen DNA’lardan TNF-A geninin promoter -376
bölgesi
polimeraz zincir reaksiyonu yöntemi ile çoğaltılmıştır.
İkinci aşamada ise elde edilen PCR ürünleri Tsp50 enzimi ile kesilerek genotip
dağılımları ve allel frekansları incelenmiştir. Türk popülasyonunda MS
hastalığı ile TNF-A    -376
polimorfizminin genotip dağılımı arasında kuvvetli bir ilişki bulunmuştur
(p=0,010). Aynı zamanda TNF-A -376 polimorfizminin allel frekansı MS
hastalığıyla bir ilişki göstermektedir (p=0.011). Bu ilişkide TNF-A -376 polimorfizminin
heterozigot genotip G/A olduğu ve A allelinin koruyucu etkisi olduğu görülmüştür.
TNF-A -376 polimorfizmi ile MS arasında hastalığın risk oluşturması açısından
herhangi bir ilişki bulunmamıştır ancak G/A genotipi ve A allelinin sağlıklı kişilerde
koruyucu etkisi olabildiği düşünülmektedir.  

Kaynakça

  • Noseworthy JH., Lucchinetti C. ve Rodriguez M., Weinshenker BG. (2000). Multiple sclerosis. N Engl J Med., 343, 938-952.
  • Dyment DA., Sadovnick AD. ve Ebers GC. (1997). Genetics of multiple sclerosis. Hum Mol Genet, 6, 1693-1698.
  • Elahi MM., Asotra K., Matata BM. ve Mastana SS. (2009). Tumor necrosis factor alpha -308 gene locus promoter polymorphism: an analysis of association with health and disease. Biochim Biophys Acta, 1792, 163-172.
  • Zipp, F., Weber, F., Huber, S., Sotgiu, S., Czlonkowska, A., Holler, E., Albert, E., Weiss, E. H., Wekerle, H., ve Hohlfeld, R. (1995). Genetic control of multiple sclerosis: increased production of lymphotoxin and tumor necrosis factor-alpha by HLA-DR2+ T cells. Ann Neurol, 38, 723-730.
  • Hurwitz BJ. (2009).The diagnosis of multiple sclerosis and the clinical subtypes. Ann Indian Acad Neurol, 12, 226-230.
  • Kassiotis G. ve Kollias G. (2001). TNF and receptors in organ-specific autoimmune disease: multi-layered functioning mirrored in animal models. J Clin Invest, 107, 1507-1508.
  • Sharief MK.ve Hentges R. (1991). Association between tumor necrosis factor-alpha and disease progression in patients with multiple sclerosis. N Engl J Med, 325, 467-472.
  • Fargion S., Valenti L., Dongiovanni P. ve Fracanzani AL. (2004). TNFalpha promoter polymorphisms. Methods Mol Med, 98, 47-58.
  • Braun, N., Michel, U., Ernst, B. P., Metzner, R., Bitsch, A., Weber, F., ve Rieckmann, P. (1996). Gene polymorphism at position -308 of the tumor-necrosis-factor-alpha (TNF-alpha) in multiple sclerosis and it's influence on the regulation of TNF-alpha production. Neurosci Lett, 215(2), 75-78.
  • Hauser, S. L. (1995). Tumor necrosis factor: immunogenetics and disease. Ann Neurol, 38(5), 702-704.
  • Weinshenker, B. G., Wingerchuk, D. M., Liu, Q., Bissonet, A. S., Schaid, D. J., ve Sommer, S. S. (1997). Genetic variation in the tumor necrosis factor alpha gene and the outcome of multiple sclerosis. Neurology, 49(2), 378-385.
  • Wingerchuk, D., Liu, Q., Sobell, J., Sommer, S., ve Weinshenker, B. G. (1997). A population-based case-control study of the tumor necrosis factor alpha-308 polymorphism in multiple sclerosis. Neurology, 49(2), 626-628.
  • Bayley, J. P., de Rooij, H., van den Elsen, P. J., Huizinga, T. W., ve Verweij, C. L. (2001). Functional analysis of linker-scan mutants spanning the -376, -308, -244, and -238 polymorphic sites of the TNF-alpha promoter. Cytokine, 14(6), 316-323.
  • de Jong, B. A., Huizinga, T. W., Zanelli, E., Giphart, M. J., Bollen, E. L., Uitdehaag, B. M., Polman, C. H., ve Westendorp, R. G. (2002). Evidence for additional genetic risk indicators of relapse-onset MS within the HLA region. Neurology, 59(4), 549-555.
  • Wirz, S. A., Morale, M. C., Marchetti, B., Barr, A. M., Sotgiu, S., Rosati, G., Pugliatti, M., Sanna, M. V., Giliberto, O., Bartfai, T., ve Conti, B. (2004). High frequency of TNF alleles -238A and -376A in individuals from northern Sardinia. Cytokine, 26(4), 149-154.
  • Fernandez-Arquero, M., Arroyo, R., Rubio, A., Martin, C., Vigil, P., Conejero, L., Figueredo, M. A., ve de la Concha, E. G. (1999). Primary association of a TNF gene polymorphism with susceptibility to multiple sclerosis. Neurology, 53(6), 1361-1363.
  • Losonczi, E., Bencsik, K., Nagy, Z. F., Honti, V., Szalczer, E., Rajda, C., Illes, Z., Matyas, K., Rozsa, C., Csepany, T., Fuvesi, J., ve Vecsei, L. (2009). Tumour necrosis factor alpha gene (TNF-alpha) -376 polymorphism in Hungarian patients with primary progressive multiple sclerosis. J Neuroimmunol, 208(1-2), 115-118.
  • Drulovic, J., Popadic, D., Mesaros, S., Dujmovic, I., Cvetkovic, I., Miljkovic, D., Stojsavljevic, N., Pravica, V., Pekmezovic, T., Bogdanovic, G., Jarebinski, M., ve Mostarica Stojkovic, M. (2003). Decreased frequency of the tumor necrosis factor alpha -308 allele in Serbian patients with multiple sclerosis. Eur Neurol, 50(1), 25-29.
  • He, B., Navikas, V., Lundahl, J., Soderstrom, M., ve Hillert, J. (1995). Tumor necrosis factor alpha-308 alleles in multiple sclerosis and optic neuritis. J Neuroimmunol, 63(2), 143-147.
  • Huizinga, T. W., Westendorp, R. G., Bollen, E. L., Keijsers, V., Brinkman, B. M., Langermans, J. A., Breedveld, F. C., Verweij, C. L., van de Gaer, L., Dams, L., Crusius, J. B., Garcia-Gonzalez, A., van Oosten, B. W., Polman, C. H., ve Pena, A. S. (1997). TNF-alpha promoter polymorphisms, production and susceptibility to multiple sclerosis in different groups of patients. J Neuroimmunol, 72(2), 149-153.
  • Ristic, S., Lovrecic, L., Starcevic-Cizmarevic, N., Brajenovic-Milic, B., Sega Jazbec, S., Sepcic, J., Kapovic, M., ve Peterlin, B. (2007). Tumor necrosis factor-alpha-308 gene polymorphism in Croatian and Slovenian multiple sclerosis patients. Eur Neurol, 57(4), 203-207.
  • Maurer, M., Kruse, N., Giess, R., Kyriallis, K., Toyka, K. V., & Rieckmann, P. (1999). Gene polymorphism at position -308 of the tumor necrosis factor alpha promotor is not associated with disease progression in multiple sclerosis patients. J Neurol, 246(10), 949-954.
  • Lassmann, H., Bruck, W., ve Lucchinetti, C. F. (2007). The immunopathology of multiple sclerosis: an overview. Brain Pathol, 17(2), 210-218.
  • Knight, J. C., Udalova, I., Hill, A. V., Greenwood, B. M., Peshu, N., Marsh, K., ve Kwiatkowski, D. (1999). A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria. Nat Genet, 22(2), 145-150.
Toplam 24 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Mühendislik
Bölüm Araştırma Makaleleri
Yazarlar

Ahmet Arman

Hasan Şimşek Bu kişi benim

Merve Sarıdal Bu kişi benim

Yayımlanma Tarihi 9 Nisan 2018
Kabul Tarihi 31 Ocak 2018
Yayımlandığı Sayı Yıl 2018 Cilt: 30 Sayı: 1

Kaynak Göster

APA Arman, A., Şimşek, H., & Sarıdal, M. (2018). Türk Popülasyonu’nda Tümor Nekroz Faktör Alfa Gen Polimorfizmi (-376) ile Multipl Skleroz Arasındaki İlişki. Marmara Fen Bilimleri Dergisi, 30(1), 50-54. https://doi.org/10.7240/marufbd.289591
AMA Arman A, Şimşek H, Sarıdal M. Türk Popülasyonu’nda Tümor Nekroz Faktör Alfa Gen Polimorfizmi (-376) ile Multipl Skleroz Arasındaki İlişki. MFBD. Mart 2018;30(1):50-54. doi:10.7240/marufbd.289591
Chicago Arman, Ahmet, Hasan Şimşek, ve Merve Sarıdal. “Türk Popülasyonu’nda Tümor Nekroz Faktör Alfa Gen Polimorfizmi (-376) Ile Multipl Skleroz Arasındaki İlişki”. Marmara Fen Bilimleri Dergisi 30, sy. 1 (Mart 2018): 50-54. https://doi.org/10.7240/marufbd.289591.
EndNote Arman A, Şimşek H, Sarıdal M (01 Mart 2018) Türk Popülasyonu’nda Tümor Nekroz Faktör Alfa Gen Polimorfizmi (-376) ile Multipl Skleroz Arasındaki İlişki. Marmara Fen Bilimleri Dergisi 30 1 50–54.
IEEE A. Arman, H. Şimşek, ve M. Sarıdal, “Türk Popülasyonu’nda Tümor Nekroz Faktör Alfa Gen Polimorfizmi (-376) ile Multipl Skleroz Arasındaki İlişki”, MFBD, c. 30, sy. 1, ss. 50–54, 2018, doi: 10.7240/marufbd.289591.
ISNAD Arman, Ahmet vd. “Türk Popülasyonu’nda Tümor Nekroz Faktör Alfa Gen Polimorfizmi (-376) Ile Multipl Skleroz Arasındaki İlişki”. Marmara Fen Bilimleri Dergisi 30/1 (Mart 2018), 50-54. https://doi.org/10.7240/marufbd.289591.
JAMA Arman A, Şimşek H, Sarıdal M. Türk Popülasyonu’nda Tümor Nekroz Faktör Alfa Gen Polimorfizmi (-376) ile Multipl Skleroz Arasındaki İlişki. MFBD. 2018;30:50–54.
MLA Arman, Ahmet vd. “Türk Popülasyonu’nda Tümor Nekroz Faktör Alfa Gen Polimorfizmi (-376) Ile Multipl Skleroz Arasındaki İlişki”. Marmara Fen Bilimleri Dergisi, c. 30, sy. 1, 2018, ss. 50-54, doi:10.7240/marufbd.289591.
Vancouver Arman A, Şimşek H, Sarıdal M. Türk Popülasyonu’nda Tümor Nekroz Faktör Alfa Gen Polimorfizmi (-376) ile Multipl Skleroz Arasındaki İlişki. MFBD. 2018;30(1):50-4.

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