Variants in the TNFA, IL6 and IFNG genes are associated with the dengue severity in a sample from Colombian population
Abstract
Introduction: The genetic makeup of the host contributes to the clinical profile of dengue. This could be due to the effect of variants in the genes encoding pro-inflammatory cytokines.
Objective: To evaluate the association between the variants of three polymorphisms in TNFA, IL6 and IFNG candidate genes with dengue severity in a sample of Colombian population.
Materials and methods: We evaluated the rs1800750, rs2069843, and rs2069705 polymorphisms in TNFA, IL6 and IFNG candidate genes, respectively, in 226 patients with dengue infection. The genotypes were typed using both polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). To determine the risk of different dengue phenotypes, we compared allele frequencies with chi-square and genotypes and haplotypes using logistic regression. Finally, these analyzes were adjusted with data from self-identification or the ancestral genetic component.
Results: The A allele in the rs2069843 polymorphism, adjusted by self-identification, was associated with dengue hemorrhagic fever cases in Afro-Colombians. In the entire sample, this polymorphism, adjusted by the ancestral genetic component, was reproducible. In addition, there were significant associations between GGT and GAC allelic combinations of rs1800750, rs2069843, and rs2069705 in dengue hemorrhagic fever patients, with and without adjustment by ancestral genetic component. Additionally, the AGC allelic combination produced 58.03 pg/ml of interleukin-6 more than the GGC combination, regardless of European, Amerindian and African genetic components.
Conclusions: The variants of GGT and GAC polymorphisms of rs1800750, rs2069843, and rs2069705 in the TNFA, IL6 and IFNG genes, respectively, were correlated with the susceptibility to dengue severity in a sample of Colombian population.
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References
World Health Organization. Dengue guidelines for diag-nosis, treatment, prevention and control. Geneva: WHO; 2009. p. 3-17.
Mangold KA, Reynolds SL. A review of dengue fever: A resurging tropical disease. Pediatr Emerg Care. 2013;29: 665-9. https://doi.org/10.1097/PEC.0b013e31828ed30e
Peña-García VH, Triana-Chávez O, Mejía-Jaramillo AM, Díaz FJ, Gómez-Palacio A, Arboleda-Sánchez S. Infection rates by dengue virus in mosquitoes and the influence of temperature may be related to different endemicity patterns in three Colombian cities. Int J Environ Res Public Health. 2016;13:734. https://doi.org/10.3390/ijerph13070734
Normile D. Tropical medicine. Surprising new dengue virus throws a spanner in disease control efforts. Science. 2013; 342:415. https://doi.org/10.1126/science.342.6157.415
Rothman AL, Currier JR, Friberg HL, Mathew A. Analysis of cell-mediated immune responses in support of dengue vaccine development efforts. Vaccine. 2014;33:7083-90. https://doi.org/10.1016/j.vaccine.2015.09.104
Balmaseda A, Hammond SN, Pérez L, Téllez Y, Saborio SI, Mercado JC, et al. Serotype-specific differences in clinical manifestations of dengue. Am J Trop Med Hyg. 2006;74:449-56.
Murgue B, Roche C, Chungue E, Deparis X. Prospective study of the duration and magnitude of viraemia in children hospitalised during the 1996-1997 dengue-2 outbreak in French Polynesia. J Med Virol. 2000;60:432-8. https://doi.org/10.1002/(SICI)1096-9071(200004)60:4<432::AID-JMV11>3.0.CO;2-7
Halstead SB, Porterfield JS, O’Rourke EJ. Enhancement of dengue virus infection in monocytes by flavivirus antisera. Am J Trop Med Hyg. 1980;29:638-42.
Alagarasu K, Damle I, Bachal R, Mulay A, Shah P, Dayaraj C. Association of promoter region polymorphisms of CD209 gene with clinical outcomes of dengue virus infection in Western India. Infect Genet Evol. 2013;17:239-42. https://doi.org/10.1016/j.meegid.2013.04.024
Restrepo BN, Ramírez RE, Arboleda M, Álvarez G, Ospina M, Díaz FJ. Serum levels of cytokines in two ethnic groups with dengue virus infection. Am J Trop Med Hyg. 2008;79:673-7.
Malavige GN, Huang LC, Salimi M, Gomes L, Jayaratne SD, Ogg GS. Cellular and cytokine correlates of severe dengue infection. PLoS One. 2012;7:1-9. https://doi.org/10. 1371/journal.pone.0050387
Castro JE, Vado-Solís I, Pérez-Osorio C, Fredeking TM. Modulation of cytokine and cytokine receptor/antagonist by treatment with doxycycline and tetracycline in patients with dengue fever. Clin Dev Immunol. 2011;2011:1-5. https://doi.org/10.1155/2011/370872
Gandini M, Reis SR, Torrentes-Carvalho A, Azeredo EL, Freire Mda S, Galler R, et al. Dengue-2 and yellow fever 17DD viruses infect human dendritic cells, resulting in an induction of activation markers, cytokines and chemokines and secretion of different TNF-alpha and IFN-alpha profiles. Mem Inst Oswaldo Cruz. 2011;106:594-605. https://doi.org/10.1590/S0074-02762011000500012
Perry ST, Buck MD, Lada SM, Schindler C, Shresta S. STAT2 mediates innate immunity to Dengue virus in the absence of STAT1 via the type I interferon receptor. PLoS Pathog. 2011;7:1-13. https://doi.org/10.1371/journal.ppat.1001297
Restrepo BN, Isaza DM, Salazar CL, Ramírez R, Ospina M, Álvarez LG. Serum levels of interleukin-6, tumor necro-sis factor-alpha and interferon-gamma in infants with and without dengue. Rev Soc Bras Med Trop. 2008;41:6-10. https://doi.org/10.1590/S0037-86822008000100002
Lan NT, Hirayama K. Host genetic susceptibility to severe dengue infection. Trop Med Health. 2011;39:73-81. http://doi.org/10.2149/tmh.2011-S08
Sessions OM, Tan Y, Goh KC, Liu Y, Tan P, Rozen S, et al. Host cell transcriptome profile during wild-type and attenuated dengue virus infection. PLoS Negl Trop Dis. 2013;7:1-12. https://doi.org/10.1371/journal.pntd.0002107
Loeb M. Genetic susceptibility to west nile virus and dengue. Public Health Genomics. 2013;16:4-8. https://doi.org/10.1159/000345934
Balding DJ. A tutorial on statistical methods for population association studies. Nat Rev Genet. 2006;7:781-91. https://doi.org/10.1038/nrg1916
Harapan H, Jonny KF, Nur W, Jay RA, Lavanya N, Kurnia FJ. Non-HLA gene polymorphisms and their implications on dengue virus infection. Egyptian Journal of Medical Human Genetics. 2013;14:1-11. https://doi.org/10.1016/j.ejmhg.2012.08.003
Cansancao IF, Carmo AP, Leite RD, Rabenhorst SH. Asso-ciation of polymorphisms in IL1beta -511C>T, IL1RN 86 bp VNTR, and IL6 -174G>C Genes with clinical dengue signs and symptoms in Brazilian dengue patients. Viral Immunol. 2016;29:372-6. https://doi.org/10.1089/vim.2015.0082
Woo P, Humphries SE. IL-6 polymorphisms: A useful genetic tool for inflammation research? J Clin Invest. 2013; 123:1413-4. https://doi.org/10.1172/JCI67221
Moreira LO, Zamboni DS. NOD1 and NOD2 signaling in infection and inflammation. Front Immunol. 2012;3:1-12. https://doi.org/10.3389/fimmu.2012.00328
Fernández-Mestre MT, Gendzekhadze K, Rivas-Vetencourt P, Layrisse Z. TNF-alpha-308A allele, a possible severity risk factor of hemorrhagic manifestation in dengue fever patients. Tissue Antigens. 2004;64:469-72. https://doi.org/10.1111/j. 1399-0039.2004.00304.x
He JR, Chen LJ, Su Y, Cen YL, Tang LY, Yu DD, et al. Joint effects of Epstein-Barr virus and polymorphisms in interleukin-10 and interferon-gamma on breast cancer risk. J Infect Dis. 2011;205:64-71. https://doi.org/10.1093/infdis/jir710
Pérez AB, Sierra B, García G, Aguirre E, Babel N, Álvarez M, et al. Tumor necrosis factor-alpha, transforming growth factor-beta1, and interleukin-10 gene polymor-phisms: Implication in protection or susceptibility to dengue hemorrhagic fever. Hum Immunol. 2010;71:1135-40. https://doi.org/10.1016/j.humimm.2010.08.004
Galanter JM, Fernández-López JC, Gignoux CR, Barnholtz-Sloan J, Fernández-Rozadilla C, Via M, et al. Development of a panel of genome-wide ancestry informative markers to study admixture throughout the Americas. PLoS Genet. 2012;8:1-16. https://doi.org/10.1371/journal.pgen. 1002554
World Health Organization. Dengue haemorrhagic fever. Diagnosis, treatment, prevention and control. Geneva: WHO; 1997. p. 12-23.
Blacksell SD, Jarman RG, Gibbons RV, Tanganuchitcharnchai A, Mammen MP Jr., Nisalak A, et al. Comparison of seven commercial antigen and antibody enzyme-linked immunosorbent assays for detection of acute dengue infection. Clin Vaccine Immunol. 2012;19:804-10. https://doi.org/10.1128/CVI.05717-11
Lanciotti RS, Calisher CH, Gubler DJ, Chang GJ, Vorndam AV. Rapid detection and typing of dengue viruses from clinical samples by using reverse transcriptase-polymerase chain reaction. J Clin Microbiol. 1992;30:545-51.
Harris E, Roberts TG, Smith L, Selle J, Kramer LD, Valle S, et al. Typing of dengue viruses in clinical specimens and mosquitoes by single-tube multiplex reverse transcriptase PCR. J Clin Microbiol. 1998;36:2634-9.
Sambrook J, Russell DW. Purification of nucleic acids by extraction with phenol:chloroform. CSH Protoc. 2006; 2006:pii. https://doi.org/10.1101/pdb.prot4455
Molokhia M, Hoggart C, Patrick AL, Shriver M, Parra E, Ye J, et al. Relation of risk of systemic lupus erythematosus to west African admixture in a Caribbean population. Hum Genet. 2003;112:310-8. https://doi.org/10.1007/s00439-002-0883-3
Shriver MD, Parra EJ, Dios S, Bonilla C, Norton H, Jovel C, et al. Skin pigmentation, biogeographical ancestry and admixture mapping. Hum Genet. 2003;112:387-99. https://doi.org/10.1007/s00439-002-0896-y
Chacón-Duque JC, Adhikari K, Avendaño E, Campo O, Ramírez R, Rojas W, et al. African genetic ancestry is associated with a protective effect on dengue severity in colombian populations. Infect Genet Evol. 2014;27:89-95. https://doi.org/10.1016/j.meegid.2014.07.003
McKeigue PM, Carpenter JR, Parra EJ, Shriver MD. Estimation of admixture and detection of linkage in admixed populations by a Bayesian approach: Application to African-American populations. Ann Hum Genet. 2000;64:171-86. https://doi.org/10.1017/S0003480000008022
Zhivotovsky LA. Relationships between Wright’s F ST and F IS statistics in a context of Wahlund effect. J Hered. 2015;106:306-9. https://doi.org/10.1093/jhered/esv019
Chua KB, Mustafa B, Abdul AH, Chem YK, Khairul AH, Kumarasamy V, et al. A comparative evaluation of dengue diagnostic tests based on single-acute serum samples for laboratory confirmation of acute dengue. Malays J Pathol. 2011;33:13-20.
Blanton RE, Silva LK, Morato VG, Parrado AR, Dias JP, Melo PR, et al. Genetic ancestry and income are asso-ciated with dengue hemorrhagic fever in a highly admixed population. Eur J Hum Genet. 2008;16:762-5. https://doi.org/10.1038/ejhg.2008.4
Clark TG, Diakite M, Auburn S, Campino S, Fry AE, Green A, et al. Tumor necrosis factor and lymphotoxin-alpha polymorphisms and severe malaria in African popu-lations. J Infect Dis. 2009;199:569-75. https://doi.org/10. 1086/596320
Ng DP, Nurbaya S, Ye SH, Krolewski AS. An IL-6 haplotype on human chromosome 7p21 confers risk for impaired renal function in type 2 diabetic patients. Kidney Int. 2008;74:521-7. https://doi.org/10.1038/ki.2008.202
Farhat SB, de Souza CM, Braosi AP, Kim SH, Tramontina VA, Papalexiou V, et al. Complete physical mapping of IL6 reveals a new marker associated with chronic periodontitis. J Periodontal Res. 2016. https://doi.org/10.1111/jre.12389
Qi L, van Dam RM, Meigs JB, Manson JE, Hunter D, Hu FB. Genetic variation in IL6 gene and type 2 diabetes: Tagging-SNP haplotype analysis in large-scale case-control study and meta-analysis. Hum Mol Genet. 2006;15:1914-20. https://doi.org/10.1093/hmg/ddl113
Fernández-Real JM, Broch M, Vendrell J, Richart C, Ricart W. Interleukin-6 gene polymorphism and lipid abnor-malities in healthy subjects. J Clin Endocrinol Metab. 2000; 85:1334-9. https://doi.org/10.1210/jcem.85.3.6555
Stahl EA, Wegmann D, Trynka G, Gutiérrez-Achury J, Do R, Voight BF, et al. Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis. Nat Genet. 2012;44:483-9. https://doi.org/10.1038/ng.2232
Restrepo BN, Ramírez R, Agudelo-Flórez PM, Avendaño-Tamayo E, Chacón-Duque JC, Rojas W, et al. Caracterís-ticas clínicas y niveles de citocinas en pacientes con dengue y su relación con la raza. Rev Biomed. 2010;21:137-47.
Silva LK, Blanton RE, Parrado AR, Melo PS, Morato VG, Reis EA, et al. Dengue hemorrhagic fever is associated with polymorphisms in JAK1. Eur J Hum Genet. 2010;18:1221-7. https://doi.org/10.1038/ejhg.2010.98
Rachman A, Rinaldi I. Coagulopathy in dengue infection and the role of interleukin-6. Acta Med Indones. 2006;38:105-8.
Woodson SE, Freiberg AN, Holbrook MR. Coagulation factors, fibrinogen and plasminogen activator inhibitor-1, are differentially regulated by yellow fever virus infection of hepatocytes. Virus Res. 2013;175:155-9. https://doi.org/10. 1016/j.virusres.2013.04.013
Rausch SM, Clark MM, Patten C, Liu H, Felten S, Li Y, et al. Relationship between cytokine gene single nucleotide polymorphisms and symptom burden and quality of life in lung cancer survivors. Cancer. 2010;116:4103-13. https://doi.org/10.1002/cncr.25255
Sinha S, Mishra SK, Sharma S, Patibandla PK, Mallick PK, Sharma SK, et al. Polymorphisms of TNF-enhancer and gene for FcgammaRIIa correlate with the severity of falciparum malaria in the ethnically diverse Indian population. Malar J. 2008;7:1-11. https://doi.org/10.1186/1475-2875-7-13
He JR, Chen LJ, Su Y, Cen YL, Tang LY, Yu DD, et al. Joint effects of Epstein-Barr virus and polymorphisms in interleukin-10 and interferon-gamma on breast cancer risk. J Infect Dis. 2012;205:64-71. https://doi.org/10.1093/infdis/jir710
Ye J, Zhu B, Fu ZF, Chen H, Cao S. Immune evasion strategies of flaviviruses. Vaccine. 2013;31:461-71. https://doi.org/10.1016/j.vaccine.2012.11.015
Kim K, Cho SK, Sestak A, Namjou B, Kang C, Bae SC. Interferon-gamma gene polymorphisms associated with susceptibility to systemic lupus erythematosus. Ann Rheum Dis. 2010;69:1247-50. https://doi.org/10.1136/ard. 2009.117572
Wang D, Zhong X, Huang D, Chen R, Bai G, Li Q, et al. Functional polymorphisms of interferon-gamma affect pneumonia-induced sepsis. PLoS One. 2014;9:1-8. https://doi.org/10.1371/journal.pone.0087049
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