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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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-B binding site, suggesting that this variant might have effect on the ability of the CFH gene to respond to signals via the NF-B 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.
Pastor, A. F., Rodrigues Moura, L., Neto, J., Nascimento, E., Calzavara-Silva, C. E., Gomes, A., ... Acioli-Santos, B.
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Pastor, André F||Rodrigues Moura, Laís||Neto, José WD||Nascimento, Eduardo JM||Calzavara-Silva, Carlos E||Gomes, Ana Lisa V||Silva, Ana Maria da||Cordeiro, Marli T||Braga-Neto, Ulisses||Crovella, Sergio||Gil, Laura HVG||Marques, Ernesto TA||Acioli-Santos, Bartolomeu
