title: A functional variant in the CD209 promoter is associated with DQ2-negative celiac disease in the Spanish population.
abstract: OBJECTIVE
  To address the role of CD209 in celiac disease (CD) patients. Non-human leukocyte antigen (HLA) genetic factors in CD predisposition are poorly understood, and environmental factors like infectious pathogens may play a role. CD209 is a dendritic and macrophage surface molecule involved in pathogen recognition and immune activation. Recently, a functional variant in the promoter of the CD209 gene (-336A/G) has been shown to affect the transcriptional CD209 activity in vitro and it has been associated with a higher susceptibility to/or severity of infection.
  
  
  METHODS
  The study population was composed of two case-control cohorts of 103 and 386 CD patients and 312 y 419 healthy controls as well as a panel of 257 celiac families. Genotyping for the -336A/G CD209 promoter polymorphism was performed using a TaqMan 5' allelic discrimination assay. HLA-DQ was determined by hybridization with allele specific probes.
  
  
  RESULTS
  Initially, the case-control and familial studies did not find any association of the -336 A/G CD209 genetic variant with CD susceptibility. However, the stratification by HLA-DQ2 did reveal a significant association of CD209 promoter polymorphism in the HLA-DQ2 (-) group (carrier A vs GG in DQ2 (-) vs DQ2 (+) patients (P = 0.026, OR = 3.71).
  
  
  CONCLUSIONS
  The -336G CD209 allele seems to be involved in CD susceptibility in HLA-DQ2 (-) patients. Our results might suggest a possible role of pathogens in the onset of a minor group of CD patients.
authors.affiliation: Servicio de Inmunología Clínica, Hospital Clínico San Carlos, Madrid 28040, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Núñez
authors.forename: B
authors.initials: B
authors.lastname: Rueda
authors.forename: A
authors.initials: A
authors.lastname: Martínez
authors.forename: C
authors.initials: C
authors.lastname: Maluenda
authors.forename: I
authors.initials: I
authors.lastname: Polanco
authors.forename: M-A
authors.initials: MA
authors.lastname: López-Nevot
authors.forename: E
authors.initials: E
authors.lastname: Ortega
authors.forename: E
authors.initials: E
authors.lastname: Sierra
authors.forename: E
authors.initials: E
authors.lastname: Gómez de la Concha
authors.forename: E
authors.initials: E
authors.lastname: Urcelay
authors.forename: J
authors.initials: J
authors.lastname: Martín
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D002446:Celiac Disease / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000502:physiology; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics* / Q000502:physiology; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics* / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000502:physiology; D012720:Severity of Illness Index; D013030:Spain / Q000453:epidemiology / Q000208:ethnology; D044465:White People / Q000235:genetics; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D006683:HLA-DQ Antigens; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C053186:HLA-DQ2 antigen