title: No evidence for association of the CD40, CD40L and BLYS polymorphisms, B-cell co-stimulatory molecules, with Brazilian endemic Plasmodium vivax malaria.
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.
authors.affiliation: Programa de Pós-Graduação em Genética, Universidade Estadual Paulista, São José do Rio Preto, São Paulo, Brasil. mpcapobianco@yahoo.com.br
authors.forename: Marcela P
authors.initials: MP
authors.lastname: Capobianco
authors.forename: Gustavo C
authors.initials: GC
authors.lastname: Cassiano
authors.forename: Adriana A C
authors.initials: AA
authors.lastname: Furini
authors.forename: Luciane M
authors.initials: LM
authors.lastname: Storti-Melo
authors.forename: Erika C
authors.initials: EC
authors.lastname: Pavarino
authors.forename: Ana L S
authors.initials: AL
authors.lastname: Galbiatti
authors.forename: Valéria D
authors.initials: VD
authors.lastname: Fraga
authors.forename: Luciana M
authors.initials: LM
authors.lastname: Conceição
authors.forename: Vanja S C
authors.initials: VS
authors.lastname: Couto
authors.forename: Alvaro A R A
authors.initials: AA
authors.lastname: Couto
authors.forename: Ricardo L D
authors.initials: RL
authors.lastname: Machado
mesh_terms: D000328:Adult; D000483:Alleles; D000953:Antigens, Protozoan / Q000235:genetics; D053264:B-Cell Activating Factor / Q000235:genetics*; D001938:Brazil; D019013:CD40 Antigens / Q000235:genetics*; D023201:CD40 Ligand / Q000235:genetics*; D016054:DNA, Protozoan / Q000032:analysis; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D016780:Malaria, Vivax / Q000235:genetics* / Q000276:immunology; D008297:Male; D010966:Plasmodium vivax / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D000953:Antigens, Protozoan; D053264:B-Cell Activating Factor; D019013:CD40 Antigens; D016054:DNA, Protozoan; D023201:CD40 Ligand
keywords: BLYS; CD40; CD40L; Malaria; Plasmodium vivax; Single nucleotide polymorphism