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

André F. Pastor, Laís Rodrigues Moura, José W D Neto, Eduardo J M Nascimento, Carlos E. Calzavara-Silva, Ana Lisa V Gomes, Ana Maria da Silva, Marli T. Cordeiro, Ulisses Braga-Neto, Sergio Crovella, Laura H V G Gil, Ernesto T A Marques, Bartolomeu Acioli-Santos

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1225-1230
Number of pages6
JournalHuman Immunology
Volume74
Issue number9
DOIs
Publication statusPublished - Sep 2013

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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