Original Article

NF-B1 Rs28362491 Mutant Allele Frequencies Along the Silk Road and Beyond

Abstract

Background: In the human evolutionary history, Single Nucleotide Polymorphism (SNP) frequencies are valuable in terms of finding connections between different populations. Due to the pronounced role of the immune system in combating pathogens and environmental stressors, polymorphisms in the immune genes are subject to selection pressure of the diseases as well. The functional polymorphisms in NF-kB1 promoter (-94 ins/del) are associated with different diseases; therefore, we aimed to establish the frequencies of NF-kB1 rs28362491 alleles in a population of Southwestern Iranians in comparison with the world populations.

Methods: We assessed the polymorphism of -94 ATTG ins/del (rs28362491) in 201 Iranian healthy blood donors from Fars Province, central Iran in a one year period between 2015 and 2016 by PCR-RFLP method using DNA extracted from peripheral blood mononuclear cells.

Results: The frequency of ins/ins homozygote genotype was found to be 46.97%. The frequency of heterozygote individuals was 42.42% and the percentage of del/del homozygote genotype was 10.61%. We observed a genetic similarity based on the genotype frequencies of NF-kB1 -94 ins/del ATTG polymorphism between our sample of Iranians with American Jewish, Turkish, American non-Jewish, Chinese-Uyghurs and Germans.

Conclusion: The results confirmed genetic interrelation of Iranians with some ancient neighbors and their admixture with countries along the Silk Road. We suggest that mapping the distribution of NF-kB1-94 ATTG ins/del along with HLA genes may help to better define the relations between human populations and design population-specific vaccines for pathogens with a high rate of variation.

 

 

Sun XF, Zhang H (2007). NFKB and NFKBI polymorphisms in relation to susceptibility of tumour and other diseases. HistolHistopathol, 22(12):1387-98.

Beinke S, Steven C Le (2004). Functions of NF-κB1 and NF-κB2 in immune cell biology. Biochem J, 382(Pt 2): 393-409.

Barnes PJ (1997). Nuclear factor-κB. IJBCB, 29(6): 867-70.

Huang TT, Kudo N, Yoshida M, Miyamoto S (2000). A nuclear export signal in the N-terminal regulatory domain of IκBα controls cytoplasmic localization of inactive NF-κB/IκBα complexes. Proc Natl Acad Sci U S A, 97(3): 1014-9.

Chen F, Castranova V, Shi X, Demers LM (1999). New insights into the role of nuclear factor-κB, a ubiquitous transcription factor in the initiation of diseases. Clin Chem, 45(1): 7-17.

Baldwin AS Jr (2001). Series introduction: the transcription factor NF-κB and human disease. J Clin Invest, 107(1): 3-6.

Bianco B, Lerner TG, Trevisan CM et al (2012). The nuclear factor-kB functional promoter polymorphism is associated with endometriosis and infertility. Hum Immunol, 73(11): 1190-3.

Stoneking M (2001). Single nucleotide polymorphisms: From the evolutionary past. Nature, 409: 821-2.

Hill AV (2012). Evolution, revolution and heresy in the genetics of infectious disease susceptibility. Philos Trans R Soc Lond B Biol, Sci 367(1590): 840-9.

Simmonds M, Gough S (2007). The HLA region and autoimmune disease: associations and mechanisms of action. Curr Genomics, 8(7): 453-65.

Laayouni H, Oosting M, Luisi P et al (2014). Convergent evolution in European and Rroma populations reveals pressure exerted by plague on Toll-like receptors. Proc Natl Acad Sci U S A, 111(7): 2668-73.

Hoffmann SC, Stanley EM, Cox ED et al (2002). Ethnicity greatly influences cytokine gene polymorphism distribution. Am J Transplant, 2(6): 560-7.

Chen LP, Cai PS, Liang HB (2015). Association of the genetic polymorphisms of NFKB1 with susceptibility to ovarian cancer. Genet Mol Res, 14: 8273-82.

Sima X, Xu J, Li J, You C (2013). Association Between NFKB1− 94 Insertion/Deletion ATTG Polymorphism and Risk of Intracranial Aneurysm. Genet Test Mol Biomarkers, 17(8): 620-4.

Yang YN, Zhang JY, Ma YT et al (2014). − 94 ATTG Insertion/Deletion Polymorphism of the NFKB1 Gene Is Associated with Coronary Artery Disease in Han and Uygur Women in China. Genet Test Mol Biomarkers, 18(6): 430-8.

Mishra A, Srivastava A, Mittal T et al (2013). Role of inflammatory gene polymorphisms in left ventricular dysfunction (LVD) susceptibility in coronary artery disease (CAD) patients. Cytokine, 61(3): 856-61.

Lewander A, Butchi AK, Gao J et al (2007). Polymorphism in the promoter region of the NFKB1 gene increases the risk of sporadic colorectal cancer in Swedish but not in Chinese populations. Scand J Gastroenterol, 42(11): 1332-8.

Karban AS, Okazaki T, Panhuysen CI et al (2004). Functional annotation of a novel NFKB1 promoter polymorphism that increases risk for ulcerative colitis. Hum Mol Genet, 13(1): 35-45.

Oltulu YM, Coskunpinar E, Ozkan G et al (2014). Investigation of NF-κB1 and NF-κBIA gene polymorphism in non-small cell lung cancer. Biomed Res Int, 2014:530381.

Fan Y, Yu W, Ye P et al (2011). NFKB1 insertion/deletion promoter polymorphism increases the risk of advanced ovarian cancer in a Chinese population. DNA Cell Biol, 30(4): 241-5.

Yalcin B AN, Alli N (2008). The functional role of nuclear factor kappa-kappaB1 -94 ins/del ATTG promotor gene polymorphism in Behçet's disease: an exploratory study Clin Exp Dermatol, 33(5): 629-33.

Gao M, Wang CH, Sima X, Han XM (2012). NFKB1 −94 Insertion/Deletion ATTG Polymorphism Contributes to Risk of Systemic Lupus Erythematosus. DNA Cell Biol, 31(4): 611-5.

Borm ME, Bodegraven AA, Mulder CJ et al (2005). A NFKB1 promoter polymorphism is involved in susceptibility to ulcerative colitis. Int J Immunogenet, 32(6): 401-5.

Glas J, Torok HP, Tonenchi L et al (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): 606-11.

Mirza MM, Fisher SA, Onnie C et al (2005). No association of the NFKB1 promoter polymorphism with ulcerative colitis in a British case control cohort. Gut, 54(8): 1205-6.

Oliver J, GómezGarcía M, Paco L et al (2005). A functional polymorphism of the NFKB1 promoter is not associated with ulcerative colitis in a Spanish population. Inflamm Bowel Dis, 11(6): 576-9.

Kurylowicz A, Hiromatsu Y, Jurecka Lubieniecka B et al (2007 ). Association of NFKB1 -94ins/del ATTG promoter polymorphism with susceptibility to and phenotype of Graves' disease. Genes Immun 8(7):532-8.

Przeworski M, Hudson RR, Di Rienzo A (2000). Adjusting the focus on human variation. Trends Genet, 16(7): 296-302.

Hughes AL, Packer B, Welch R et al (2005). Effects of natural selection on interpopulation divergence at polymorphic sites in human protein-coding loci. Genetics, 170(3): 1181-7.

Udalova IA, Richardson A, Denys A et al (2000). Functional consequences of a polymorphism affecting NF-κB p50-p50 binding to the TNF promoter region. Mol Cell Biol, 20(24): 9113-9.

Mummidi S, Bamshad M, Ahuja SS et al (2000). Evolution of human and non-human primate CC chemokine receptor 5 gene and mRNA Potential roles for haplotype and mRNA diversity, differential haplotype-specific transcriptional activity, and altered transcription factor binding to polymorphic nucleotides in the pathogenesis of HIV-1 and simian immunodeficiency virus. J Biol Chem, 275(25): 18946-61.

Liu R, Zhao X, Gurney TA, Landau NR (1998). Functional analysis of the proximal CCR5 promoter. AIDS Res Hum Retroviruses, 14(17): 1509-19.

Eskandari Nasab E, Hashemi M, Ebrahimi M, Amininia S (2016). The functional 4-bp insertion/deletion ATTG polymorphism in the promoter region of NF-B1 reduces the risk of BC. Cancer Biomark, 16(1):109-15.

Zahednasab H, Mesbah Namin SA, Sahraian MA et al (2013). Relationship between NF-κB1− 94 ins/del ATTG polymorphism and susceptibility of multiple sclerosis in Iranian MS patients. Neurosci Lett, 545: 46-9.

Pezeshki A, Sari Aslanl F, Ghaderi A, Doroudchi M (2006). p53 codon 72 polymorphism in basal cell carcinoma of the skin. Pathol Oncol Res, 12(1): 29-33.

Kayaaltı Z, Söylemezoğlu T (2010). Distribution of ADH1B, ALDH2, CYP2E1∗6, and CYP2E1∗7B genotypes in Turkish population. Alcohol, 44(5): 415-23.

Ablimit A, Qin W, Shan W et al (2013). Genetic diversities of cytochrome B in Xinjiang Uyghur unveiled its origin and migration history. BMC Genet, 14(1): 100.

Barreiro LB, Quintana Murci L (2010). From evolutionary genetics to human immunology: how selection shapes host defence genes. Nat Rev Genet, 11(1): 17-30.

Shapira M (2016). Gut Microbiotas and Host Evolution: Scaling Up Symbiosis. Trends Ecol Evol, 31(7):539-549.

Chen CC, Lu RB, Chen YC et al (1999). Interaction between the functional polymorphisms of the alcohol-metabolism genes in protection against alcoholism. Am J Hum Genet, 65(3): 795-807.

Broushaki F, Thomas MG, Link V et al (2016). Early Neolithic genomes from the eastern Fertile Crescent. Science, 353(6298):499-503.

Mohammadi J, Pourpak Z, Jarefors S et al (2008). Human leukocyte antigens (HLA) associated with selective IgA deficiency in Iran and Sweden. Iran J Allergy Asthma Immunol, 7(4):209-14.

Zoossmann Diskin A (2010). The origin of Eastern European Jews revealed by autosomal, sex chromosomal and mtDNA polymorphisms. Biol Direct, 5: 57.

Amirzargar A, Mytilineos J, Farjadian S et al (2001). Human leukocyte antigen class II allele frequencies and haplotype association in Iranian normal population. Hum Immunol, 62(11): 1234-8.

Amirzargar AA, Naroueynejad M, Khosravi F et al (2008). Cytokine single nucleotide polymorphisms in Iranian populations. Eur Cytokine Netw, 19(2):104-12.

Payan M, Tajik N, Rouini MR, Ghahremani MH (2015). Genotype and allele frequency of CYP2C19* 17 in a healthy Iranian population. Med J Islam Repub Iran, 29: 269.

Atzmon G, Hao L, Pe'er I et al (2010). Abraham's children in the genome era: major Jewish diaspora populations comprise distinct genetic clusters with shared Middle Eastern Ancestry. Am J Hum Genet, 86(6):850-9.

Nei M, Roychoudhury AK (1993). Evolutionary relationships of human populations on a global scale. Mol Biol Evol, 10(5): 927-43.

Marques CF, Koifman S, Koifman RJ et al (2006). Influence of CYP1A1, CYP2E1, GSTM3 and NAT2 genetic polymorphisms in oral cancer susceptibility: results from a case-control study in Rio de Janeiro. Oral Oncol, 42(6): 632-7.

Bernal ML, Sinues B, Fanlo A, Mayayo E (2003). Frequency distribution of C3435T mutation in exon 26 of the MDR1 gene in a Spanish population. Ther Drug Monit, 25(1):107-11.

Bonizzi G, Karin M (2004). The two NF-κB activation pathways and their role in innate and adaptive immunity. Trends Immunol, 25(6): 280-8.

Temperley ND, Berlin S, Paton IR et al (2008). Evolution of the chicken Toll-like receptor gene family: a story of gene gain and gene loss. BMC Genomics, 9: 62.

Werling D, Jann OC, Offord V et al (2009). Variation matters: TLR structure and species-specific pathogen recognition. Trends Immunol, 30(3): 124-30.

Burnik FS, Yalçın Ş (2009). NFKB1–94 insertion/deletion ATTG polymorphism in gastroenteropancreatic neuroendocrine tumors. Chemotherapy, 55(5): 381-5.

Koc A, Batar B, Celik O et al (2014). Polymorphism of the NFKB1 affects the serum inflammatory levels of IL-6 in Hashimoto thyroiditis in a Turkish population. Immunobiology, 219(7): 531-6.

Lin SC, Liu CJ, Yeh WI et al (2006). Functional polymorphism in NFKB1 promoter is related to the risks of oral squamous cell carcinoma occurring on older male areca (betel) chewers. Cancer Lett, 243(1): 47-54.

Lo SS, Chen JH, Wu CW, Lui WY (2009). Functional polymorphism of NFKB1 promoter may correlate to the susceptibility of gastric cancer in aged patients. Surgery, 145(3): 280-5.

He Y, Zhang H, Yin J et al (2009). IkappaBalpha gene promoter polymorphisms are associated with hepatocarcinogenesis in patients infected with hepatitis B virus genotype C. Carcinogenesis: 30(11):1916-22.

Zhang P, Wei Q, Li X et al (2009). A functional insertion/deletion polymorphism in the promoter region of the NFKB1 gene increases susceptibility for prostate cancer. Cancer Genet Cytogenet, 191(2): 73-7.

Zhou B, Qie M, Wang Y et al (2010). Relationship between NFKB1− 94 insertion/deletion ATTG polymorphism and susceptibility of cervical squamous cell carcinoma risk. Annal Oncol, 21(3):506-11.

Cai H, Sun L, Cui L, et al (2013). A functional insertion/deletion polymorphism (-94 ins/del ATTG) in the promoter region of the NFKB1 gene is related to the risk of renal cell carcinoma. Urol Int, 91(2): 206-12.

Cheng CW, Su JL, Lin CW et al (2013). Effects of NFKB1 and NFKBIA gene polymorphisms on hepatocellular carcinoma susceptibility and clinicopathological features. PLoS One, 8(2): e56130.

Riemann K, Becker L, Struwe H et al (2007). Insertion/deletion polymorphism in the promoter of NFKB1 as a potential molecular marker for the risk of recurrence in superficial bladder cancer. Int J Clin Pharmacol Ther, 45(8): 423-30.

Mohd Suzairi MS, Tan SC, Ahmad Aizat AA et al (2013). The functional −94 insertion/deletion ATTG polymorphism in the promoter region of NFKB1 gene increases the risk of sporadic colorectal cancer. Cancer Epidemiol, 37(5): 634-8.

Zhou B, Rao L, Peng Y et al (2010). A functional promoter polymorphism in NFKB1 increases susceptibility to endometriosis. DNA Cell Biol, 29(5): 235-9.

Andersen V, Christensen J, Ernst A et al (2011). Polymorphisms in NF-kappa B, PXR, LXR, PPAR gamma and risk of inflammatory bowel disease. World J Gastroenterol, 17(2): 197-206.

Marcos M, Pastor I, González‐Sarmiento R, Laso FJ (2009). A functional polymorphism of the NFKB1 gene increases the risk for alcoholic liver cirrhosis in patients with alcohol dependence. Alcohol Clin Exp Res, 33(11): 1857-62.

Bu H, Rosdahl I, Sun XF, Zhang H (2007). Importance of polymorphismsin NF-kappaB1 and NF-kappaBI alpha genes for melanoma risk, clinicopathological features and tumor progression in Swedish melanoma patients. J Cancer Res Clin Oncol, (133): 859-66.

Ungerbäck J, Belenki D, Fredrikson M et al (2012). Genetic variation and alterations of genes involved in NFκB/TNFAIP3-and NLRP3-inflammasome signaling affect susceptibility and outcome of colorectal cancer. Carcinogenesis, 33(11): 2126-34.

Files
IssueVol 47 No 3 (2018) QRcode
SectionOriginal Article(s)
Keywords
NF-kB1 Polymorphism Normal population PCR–RFLP Iran

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
PORDEL S, NEMATI K, KARIMI MH, DOROUDCHI M. NF-B1 Rs28362491 Mutant Allele Frequencies Along the Silk Road and Beyond. Iran J Public Health. 2018;47(3):397-406.