title: 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.
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.
authors.affiliation: Virology and Experimental Therapy Laboratory, FIOCRUZ-PE, Recife, Brazil.
authors.forename: André F
authors.initials: AF
authors.lastname: Pastor
authors.forename: Laís
authors.initials: L
authors.lastname: Rodrigues Moura
authors.forename: José W D
authors.initials: JW
authors.lastname: Neto
authors.forename: Eduardo J M
authors.initials: EJ
authors.lastname: Nascimento
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Calzavara-Silva
authors.forename: Ana Lisa V
authors.initials: AL
authors.lastname: Gomes
authors.forename: Ana Maria da
authors.initials: AM
authors.lastname: Silva
authors.forename: Marli T
authors.initials: MT
authors.lastname: Cordeiro
authors.forename: Ulisses
authors.initials: U
authors.lastname: Braga-Neto
authors.forename: Sergio
authors.initials: S
authors.lastname: Crovella
authors.forename: Laura H V G
authors.initials: LH
authors.lastname: Gil
authors.forename: Ernesto T A
authors.initials: ET
authors.lastname: Marques
authors.forename: Bartolomeu
authors.initials: B
authors.lastname: Acioli-Santos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D017242:Complement Factor H / Q000235:genetics*; D003715:Dengue / Q000235:genetics* / Q000276:immunology; D003716:Dengue Virus / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D016328:NF-kappa B; D017242:Complement Factor H
keywords: CFH; DENV; DF; OR; SD; complement factor H; dengue fever; dengue virus; odds ratio; severe dengue