title: Replication study of 10 genes showing evidence for association with multiple sclerosis: validation of TMEM39A, IL12B and CBLB [correction of CLBL] genes.
abstract: OBJECTIVE
  Ten genes previously showing different evidence of association with multiple sclerosis have been selected to validate.
  
  
  METHODS
  Eleven polymorphisms were genotyped with the iPLEX™ Sequenom in a well-powered collection of Spanish origin including 2863 multiple sclerosis cases and 2930 controls.
  
  
  RESULTS
  Replication extended to the following polymorphisms: PKN2 (rs305217), GTF2B (rs7538427), EPHA4 (rs1517440), YTHDF3 (rs12115114), ANKFN1 (rs17758761) and PTPRM (rs4798571), which did not reach the threshold of significance in a follow-up of the first genome-wide association study (GWAS) conducted in multiple sclerosis; TMEM39A (rs1132200), which appeared as a newly identified susceptibility gene in the same study; a gene previously reaching GWAS significance in Italy, CBLB (rs9657904); IL12B (rs6887695, rs10045431), a susceptibility gene shared by diverse autoimmune diseases and, finally, another gene showing inconclusive association with multiple sclerosis, CNR1 (rs1049353).
  
  
  CONCLUSIONS
  Pooled analysis corroborated the effect on MS predisposition of three genes: TMEM39A [rs1132200: p(M-H)=0.001; OR(M-H) (95% CI)= 0.84 (0.75-0.93)], IL12B [rs6887695: p(M-H)=0.03; OR(M-H) (95% CI)= 1.09 (1.01-1.17)] and CBLB [rs9657904: p(M-H)=0.01; OR(M-H) (95% CI)= 0.89 (0.81-0.97)].
authors.affiliation: Immunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Spain.
authors.forename: Jezabel
authors.initials: J
authors.lastname: Varadé
authors.forename: Manuel
authors.initials: M
authors.lastname: Comabella
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Ortiz
authors.forename: Rafael
authors.initials: R
authors.lastname: Arroyo
authors.forename: Oscar
authors.initials: O
authors.lastname: Fernández
authors.forename: M Jesús
authors.initials: MJ
authors.lastname: Pinto-Medel
authors.forename: María
authors.initials: M
authors.lastname: Fedetz
authors.forename: Guillermo
authors.initials: G
authors.lastname: Izquierdo
authors.forename: Miguel
authors.initials: M
authors.lastname: Lucas
authors.forename: Carlos López
authors.initials: CL
authors.lastname: Gómez
authors.forename: Antonio Catalá
authors.initials: AC
authors.lastname: Rabasa
authors.forename: Antonio
authors.initials: A
authors.lastname: Alcina
authors.forename: Fuencisla
authors.initials: F
authors.lastname: Matesanz
authors.forename: Iraide
authors.initials: I
authors.lastname: Alloza
authors.forename: Alfredo
authors.initials: A
authors.lastname: Antigüedad
authors.forename: María
authors.initials: M
authors.lastname: García-Barcina
authors.forename: David
authors.initials: D
authors.lastname: Otaegui
authors.forename: Javier
authors.initials: J
authors.lastname: Olascoaga
authors.forename: Albert
authors.initials: A
authors.lastname: Saiz
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Blanco
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalbán
authors.forename: Koen
authors.initials: K
authors.lastname: Vandenbroeck
authors.forename: Elena
authors.initials: E
authors.lastname: Urcelay
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40; D008565:Membrane Proteins; C550347:TMEM39A protein, human; C492211:CBLB protein, human; D050721:Proto-Oncogene Proteins c-cbl