Abstract
A polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) assay was used in a Turkish population to determine the frequency of polymorphisms of the nuclear factor-kappa (NF-κB1) and NF-κBIA genes, which have been shown to be related to several inflammatory diseases and cancer pathogenesis. Total genomic DNA was isolated from peripheral blood samples taken from 565 healthy volunteers living in Aydın Province. The genomic regions in question were amplified by PCR, and the polymorphisms in these regions were detected by a PCR–RFLP assay. The frequencies were 10.3% for the NF-κB1 −94ins/delATTG del/del genotype, 49.1% for del/ins, and 40.6% for ins/ins. The genotype frequencies of the NF-κBIA 3′UTR A → G genotypes were A/A 19.2%, A/G 42.3%, and G/G 38.5%. Distribution of genotype frequencies was tested by Hardy–Weinberg; the NF-κB1 gene was in Hardy–Weinberg equilibrium (χ2 = 3.402, P > 0.05), the NF-κBIA gene was not (χ2 = 8.293, P < 0.05).
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References
Bauerle PA (1998) IkappaB-NF-kappaB structures: at the interface of inflammation control. Cell 95:729–731
Blank V, Kourilsky P, Israel A (1992) NF-kappa B and related proteins: Rel/dorsal homologies meet ankyrin-like repeats. Trends Biochem Sci 17:135–140
Bu H, Rosdahl I, Sun X-F, Zhang H (2007) Importance of polymorphism in NF-κB1 and NF-κBIα genes for melanoma risk, clinicopathological features and tumor progression in Swedish melanoma patients. J Cancer Res Clin Oncol 133(11):859–866
Campbell KJ, Perkins ND (2006) Regulation of NF-kappaB function. Biochem Soc Symp 73:165–180
Chiao PJ, Miyamoto S, Verma IM (1994) Autoregulation of IκBα activity. Proc Natl Acad Sci USA 91:28–32
Curran JE, Weinstein SR, Griffiths LR (2002) Polymorphic variants of NFKB1 and its inhibitory protein NFKBIA, and their involvement in sporadic breast cancer. Cancer Lett 188(1–2):103–107
Feinman R, Siegel DS, Berenson J (2004) Regulation of NF-kB in multiple myeloma: therapeutic implications. Clin Adv Hematol Oncol 2(3):162–166
Gao J, Pfeifer D, He L-J, Qiao F, Zhang Z, Arbman G, Wang ZL, Jia CR, Carstensen J, Sun XF (2007) Association of NFKBIA polymorphism with colorectal cancer risk and prognosis in Swedish and Chinese population. Scand J Gastroenterol 42:345–350
Glas J, Török HP, Tonenchi L, Müller-Myhsok B, Mussack T, Wetzke M, Klein W, Epplen JT, Griga T, Schiemann U, Lohse P, Seiderer J, Schnitzler F, Brand S, Ochsenkühn T, Folwaczny M, Folwaczny C (2006) Role of the NFKB1–94ins/delATTG promoter polymorphism in IBD and potential interactions with polymorphisms in the CARD15/NOD2, IKBL, and IL-1RN genes. Inflamm Bowel Dis 12(7):606–611
Glavac D, Ravnik-Glavac M, O’Brien SJ, Dean M (1994) Polymorphisms in the 3′ untranslated region of the IκB/MAD-3 (NFKBI) gene located on chromosome 14. Hum Genet 93(6):694–696
Heron E, Deloukas P, Van Loon AP (1995) The complete exon-intron structure of the 150 kb human gene NFKB1, which encodes p105 and p50 proteins of transcription factors NF-kappaB and I-kappa B-gama: implications for NF-kappa B-mediated signal transduction. Genomics 30:493
Karban AS, Okazaki T, Panhuysen CIM, Gallegos T, Potter JJ, Bailey-Wilson JE, Silverberg MS, Duerr RH, Cho JH, Gregersen PK, Wu Y, Achkar JP, Dassopoulos T, Mezey E, Bayless TM, Nouvet FJ, Brant SR (2004) Functional annotation of a novel NFKB1 promoter polymorphism that increases risk for ulcerative colitis. Hum Mol Genet 13(1):35–45
Klein W, Tromm A, Folwaczny C, Hagedorn M, Duerig N, Epplen JT, Schmiegel WH, Griga T (2004) A polymorphism of the NFKBIA gene is associated with Crohn’s disease patients lacking a predisposing allele of the CARD15 gene. Int J Colorectal Dis 19:153–156
Kurylowicz A, Hiromatsu Y, Jurecka-Lubieniecka B, Kula D, Kowalska M, Ichimura M, Koga H, Kaku H, Bar-Andziak E, Nauman J, Jarzab B, Plosk R, Bednarczuk T (2007) Association of NFKB1–94ins/del ATTG promoter polymorphism with susceptibility to and phenotype of Graves’ disease. Genes Immun 8:532–538
Levene H (1949) On a matching problem arising in genetics. Ann Math Stat 20(1):91–94
Lin CH, Ou TT, Wu CC, Tsai WC, Liu HW, Yen JH (2007) IκBα promoter polymorphisms in patients with rheumatoid arthritis. Int J Immunogenet 34(1):51–54
Mirza MM, Fisher SA, Onnie C, Lewis CM, Mathew CG, Sanderson J, Forbes A (2005) No association of the NFKB1 promoter polymorphism with ulcerative colitis in a British case control cohort. Br Med J 54:1205–1206
Nakshatri H, Bhat-Nakshatri P, Martin DA, Goulet RJ Jr, Sledge GW Jr (1997) Constitutive activation of NF-kB during progression of breast cancer to hormone-independent growth. Mol Cell Biol 17:3629–3639
Orozco G, Sánchez E, Collado MD, López-Nevot MÁ, Paco L, García A, Jiménez-Alonso J, Martín J (2005) Analysis of the functional NFKB1 promoter polymorphism in rheumatoid arthritis and systemic lupus erythematosus. Tissue Antigens 65(2):183–186
Pahl HL (1999) Activators and target genes of Rel/NF-κB transcription factors. Oncogene 18:6853–6866
Parker KM, Ma MH, Manyak S, Altamirano CV, Tang YM, Frantzen M, Mikail A, Roussos E, Sjak-Shie N, Vescio RA, Berenson JR (2002) Identification of polymorphisms of the IκBα gene associated with an increased risk of multiple myeloma. Cancer Genet Cytogenet 137:43–48
Rayet B, Gelinas C (1999) Aberrant rel/nfkb genes and activity in human cancer. Oncogene 18:6938–6947
Richmond A (2002) Nf-kappa B, chemokine gene transcription and tumour growth. Nat Rev Immunol 2(9):664–674
Romzova M, Hohenadel D, Kolostova K, Pinterova D, Fojtikova M, Ruzickova S, Dostal C, Bosak V, Rychlik I, Cerna M (2006) NFκB and its inhibitor IκB in relation to type 2 diabetes and its microvascular and atherosclerotic complications. Hum Immunol 67(9):706–713
Sen R, Baltimore D (1986) Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell 47(6):921–928
Shattuck-Brandt RL, Richmond A (1997) Enhanced degradation of IkappaB alpha contributes to endogenous activation of NF-kappaB in Hs294T melanoma cells. Cancer Res 57(14):3032–3039
Ulusoy M, Tunçbilek E (1987) Türkiye’de akraba evlilikleri ve çocuk ölümlerine etkisi. Nüfusbilim Derg 9:7–26
Yang J, Richmond A (2001) Constitutive IkappaB kinase activity correlates with nuclear factor-kappaB activation in human melanoma cells. Cancer Res 61(12):4901–4909
Acknowledgments
We thank the Turkish Red Crescent for permission to collect blood samples from volunteer blood donors. This work was financially supported by the Scientific Research Projects Unit of Adnan Menderes University, Turkey.
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Senol Tuncay, S., Okyay, P. & Bardakci, F. Identification of NF-κB1 and NF-κBIΑ Polymorphisms Using PCR–RFLP Assay in a Turkish Population. Biochem Genet 48, 104–112 (2010). https://doi.org/10.1007/s10528-009-9302-y
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DOI: https://doi.org/10.1007/s10528-009-9302-y