No evidence for association of the CD40, CD40L and BLYS polymorphisms, B-cell co-stimulatory molecules, with Brazilian endemic Plasmodium vivax malaria

Trans R Soc Trop Med Hyg. 2013 Jun;107(6):377-83. doi: 10.1093/trstmh/trt031. Epub 2013 Apr 19.

Abstract

Background: Plasmodium vivax is the most prevalent malaria species in Brazil. The parasite-host coevolutionary process can be viewed as an 'arms race', in which adaptive genetic changes in one are eventually matched by alterations in the other.

Methods: Following the candidate gene approach we analyzed the CD40, CD40L and BLYS genes that participate in B-cell co-stimulation, for associations with P. vivax malaria. The study sample included 97 patients and 103 controls. We extracted DNA using the extraction and purification commercial kit and identified the following SNPs: -1C > T in the CD40 gene, -726T > C in the CD40L gene and the -871C > T in the BLyS gene using PCR-RFLP. We analyzed the genotype and allele frequencies by direct counting. We also compared the observed with the expected genotype frequencies using the Hardy-Weinberg equilibrium.

Results: The allele and genotype frequencies for these SNPs did not differ statistically between patient and control groups. Gene-gene interactions were not observed between the CD40 and BLYS and between the CD40L and BLYS genes. Overall, the genes were in Hardy-Weinberg equilibrium. Significant differences were not observed among the frequencies of antibody responses against P. vivax sporozoite and erythrocytic antigens and the CD40 and BLYS genotypes.

Conclusions: The results of this study show that, although the investigated CD40, CD40L and BLYS alleles differ functionally, this variation does not alter the functionality of the molecules in a way that would interfere in susceptibility to the disease. The variants of these genes may influence the clinical course rather than simply increase or decrease susceptibility.

Keywords: BLYS; CD40; CD40L; Malaria; Plasmodium vivax; Single nucleotide polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Antigens, Protozoan / genetics
  • B-Cell Activating Factor / genetics*
  • Brazil
  • CD40 Antigens / genetics*
  • CD40 Ligand / genetics*
  • DNA, Protozoan / analysis
  • Disease Progression
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Logistic Models
  • Malaria, Vivax / genetics*
  • Malaria, Vivax / immunology
  • Male
  • Plasmodium vivax / genetics*
  • Polymorphism, Single Nucleotide*
  • Young Adult

Substances

  • Antigens, Protozoan
  • B-Cell Activating Factor
  • CD40 Antigens
  • DNA, Protozoan
  • CD40 Ligand