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Hum Immunol. 2013 Sep;74(9):1225-30. doi: 10.1016/j.humimm.2013.05.005. Epub 2013 Jun 6.

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.

Author information

1
Virology and Experimental Therapy Laboratory, FIOCRUZ-PE, Recife, Brazil.

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.

KEYWORDS:

CFH; DENV; DF; OR; SD; complement factor H; dengue fever; dengue virus; odds ratio; severe dengue

PMID:
23747994
PMCID:
PMC3909654
DOI:
10.1016/j.humimm.2013.05.005
[Indexed for MEDLINE]
Free PMC Article

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