Complement factor H gene (CFH) polymorphisms C-257T, G257A and haplotypes are associated with protection against Severe Dengue Phenotype, possible related with high CFH expression

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Type: Journal Publication

Web: http://www.ncbi.nlm.nih.gov/pubmed/23747994


Abstract: Four genetic polymorphisms located at the promoter (C-257T) and coding regions of CFH gene (exon 2 G257A, exon 14 A2089G and exon 19 G2881T) were investigated in 121 dengue patients (DENV-3) in order to assess the relationship between allele/haplotypes variants and clinical outcomes. A statistical value was found between the CFH-257T allele (TT/TC genotypes) and reduced susceptibility to severe dengue (SD). Statistical associations indicate that individuals bearing a T allele presented significantly higher protein levels in plasma. The −257T variant is located within a NF-κB binding site, suggesting that this variant might have effect on the ability of the CFH gene to respond to signals via the NF-κB pathway. The G257A allelic variant showed significant protection against severe dengue. When CFH haplotypes effect was considered, the ancestral CG/CG promoter-exon 2 SNP genotype showed significant risk to SD either in a general comparison (ancestral × all variant genotypes), as well as in individual genotypes comparison (ancestral × each variant genotype), where the most prevalent effect was observed in the CG/CG × CA/TG comparison. These findings support the involvement of −257T, 257A allele variants and haplotypes on severe dengue phenotype protection, related with high basal CFH expression.


Cited as: A.F. Pastor, L. Rodrigues, J.W.D. Neto, E.J.M. Nascimento, C.E. Calzavara-Silva, A.L.V. Gomes, A.M. da Silva, M.T. Cordeiro, U.M. Braga-Neto, S. Crovella, L.H.V.G. Gil, B. Acioli-Santos, E.T.A. Marques Jr., "Complement factor H gene (CFH) polymorphisms C-257T, G257A and haplotypes are associated with protection against Severe Dengue Phenotype, possible related with high CFH expression", Human Immunology Volume 74, Issue 9, September 2013, Pages 1225–1230

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