title: Human Polymorphisms in Placentally Expressed Genes and Their Association With Susceptibility to Congenital Trypanosoma cruzi Infection.
abstract: BACKGROUND
  It is currently unclear why only a proportion of children born to Trypanosoma cruzi-infected mothers acquire the infection. We have examined the association of 11 single-nucleotide polymorphisms (SNPs) located in genes coding for placental expression enzymes as genetic markers of susceptibility to congenital T. cruzi infection (hereafter, "congenital infection"): rs2014683 and rs1048988 in ALPP; rs11244787 and rs1871054 in ADAM12; rs243866, rs243865, rs17859821, rs243864, and rs2285053 in MMP2; and rs3918242 and rs2234681 in MMP9.
  
  
  METHODS
  Two groups of children born to mothers seropositive for T. cruzi were compared: 101 had congenital infection, and 116 were uninfected. Novel high-resolution melting and capillary electrophoresis genotyping techniques were designed and used.
  
  
  RESULTS
  Logistic regression analysis showed that mutations in rs11244787 and rs1871054 (in ADAM12) and rs243866, rs17859821, and rs2285053 (in MMP2) were associated with susceptibility to congenital infection. Multifactor dimensionality reduction revealed that genotyping results for rs11244787, rs1871054, rs243866, rs17859821 and rs243864 sites would be a good predictor of congenital infection.
  
  
  CONCLUSIONS
  Our results suggest an important role of human polymorphisms in proteins involved in extracellular matrix remodeling and the immune response during congenital infection. To our knowledge, this is the first study demonstrating the association between mutations in placentally expressed genes and susceptibility to congenital infection.
authors.affiliation: Grupo de Biología Molecular de la Enfermedad de Chagas, Instituto de Investigaciones en Ingeniería Genética y Biología Molecular Dr Héctor N. Torres.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Juiz
authors.affiliation: Instituto de Biología de la Altura, Universidad Nacional de Jujuy.
authors.forename: Nelly M
authors.initials: NM
authors.lastname: Cayo
authors.affiliation: Servicio de Obstetricia, Departamento Materno Infantil, Hospital Nacional Profesor Alejandro Posadas.
authors.forename: Marianela
authors.initials: M
authors.lastname: Burgos
authors.affiliation: Servicio de Obstetricia, Departamento Materno Infantil, Hospital Nacional Profesor Alejandro Posadas.
authors.forename: Miriam E
authors.initials: ME
authors.lastname: Salvo
authors.affiliation: Laboratorio de Química Biológica, Facultad de Ciencias Naturales, Universidad Nacional de Salta, Argentina.
authors.forename: Julio R
authors.initials: JR
authors.lastname: Nasser
authors.affiliation: Instituto Nacional de Parasitología Dr Mario Fatala Chaben, ANLIS, Buenos Aires.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Búa
authors.affiliation: Grupo de Biología Molecular de la Enfermedad de Chagas, Instituto de Investigaciones en Ingeniería Genética y Biología Molecular Dr Héctor N. Torres.
authors.forename: Silvia A
authors.initials: SA
authors.lastname: Longhi
authors.affiliation: Grupo de Biología Molecular de la Enfermedad de Chagas, Instituto de Investigaciones en Ingeniería Genética y Biología Molecular Dr Héctor N. Torres.
authors.forename: Alejandro G
authors.initials: AG
authors.lastname: Schijman
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D014355:Chagas Disease / Q000453:epidemiology* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016015:Logistic Models; D008666:Metalloendopeptidases / Q000235:genetics; D009035:Mothers; D010920:Placenta / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011247:Pregnancy; D014349:Trypanosoma cruzi
chemical_list: D008666:Metalloendopeptidases
keywords: ADAM12; ALPP; MMP2; MMP9; SNPs; congenital Chagas