title: A multicentric association study between 39 genes and nonsyndromic cleft lip and palate in a Brazilian population.
abstract: OBJECTIVE
  The aim of this study was to use the TaqMan OpenArray system to evaluate associations between 39 genes and the etiology of nonsyndromic cleft lip and palate (NSCLP) in a Brazilian population.
  
  
  METHODS
  This case-control association study was designed with 80.11% statistical power according to logistic regression (GPOWER software). The case group had 182 patients with NSCLP enrolled in the Brazilian Database on Orofacial Clefts. The controls included 355 healthy individuals with no history of oral clefting in the past three generations. All samples were genotyped for 253 tag single nucleotide polymorphisms (tagSNPs) in 39 genes, including two that had recently been associated with this process. The association analysis was performed using logistic regression and stepwise regression. The results were corrected for multiple testing [Bonferroni correction and False Discovery Rate (FDR)].
  
  
  RESULTS
  Twenty-four SNPs in 16 genes were significantly associated with the etiology of NSCLP, including MSX1, SPRY1, MSX2, PRSS35, TFAP2A, SHH, VAX1, TBX10, WNT11, PAX9, BMP4, JAG2, AXIN2, DVL2, KIF7, and TCBE3. Stepwise regression analysis revealed that 11 genes contributed to 15.5% of the etiology of NSCLP in the sample.
  
  
  CONCLUSIONS
  This is the first study to associate KIF7 and TCEB3 with the etiology of NSCLP. New technological approaches using the same design should help to identify further etiological susceptibility variants.
authors.affiliation: Department of Medical Genetics, Faculty of Medical Sciences, University of Campinas (UNICAMP), 13083-887 Campinas, SP, Brazil.
authors.forename: Tânia Kawasaki
authors.initials: TK
authors.lastname: de Araujo
authors.affiliation: Department of Medical Genetics, Faculty of Medical Sciences, University of Campinas (UNICAMP), 13083-887 Campinas, SP, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Secolin
authors.affiliation: Medical Genetics Service, Hospital de Clinicas de Porto Alegre, 90035-903 Porto Alegre, RS, Brazil.
authors.forename: Têmis Maria
authors.initials: TM
authors.lastname: Félix
authors.affiliation: Medical Genetics Service, Hospital de Clinicas de Porto Alegre, 90035-903 Porto Alegre, RS, Brazil.
authors.forename: Liliane Todeschini
authors.initials: LT
authors.lastname: de Souza
authors.affiliation: Medical Genetics Sector, State University of Alagoas (UNCISAL), 57010-300 Maceió, AL, Brazil.
authors.forename: Marshall Ítalo Barros
authors.initials: MÍ
authors.lastname: Fontes
authors.affiliation: Clinical Genetics Service, Faculty of Medicine, University Hospital, Federal University of Alagoas (UFAL), 57072-970 Maceió, AL, Brazil.
authors.forename: Isabella Lopes
authors.initials: IL
authors.lastname: Monlleó
authors.affiliation: Centro de Atendimento Integral ao Fissurado Labiopalatal (CAIF), 81050-00 Curitiba, PR, Brazil.
authors.forename: Josiane
authors.initials: J
authors.lastname: de Souza
authors.affiliation: Department of Molecular Biology, Medical School in São José do Rio Preto (FAMERP FUNFARME), 15090-000 São José do Rio Preto, SP, Brazil.
authors.forename: Agnes Cristina
authors.initials: AC
authors.lastname: Fett-Conte
authors.affiliation: Medical Genetics Service, Hospital Infantil Albert Sabin - HIAS, 60410-790 Fortaleza, CE, Brazil.
authors.forename: Erlane Marques
authors.initials: EM
authors.lastname: Ribeiro
authors.affiliation: Center for Research and Rehabilitation of Lip and Palate Lesions (CRRLPL), Centrinho Prefeito Luiz Gomes, 89203-020 Joinville, SC, Brazil.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Xavier
authors.affiliation: Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, Hospital Onofre Lopes (HUOL), Federal University of Rio Grande do Norte (UFRN), 59012-570 Natal, RN, Brazil.
authors.forename: Adriana Augusto
authors.initials: AA
authors.lastname: de Rezende
authors.affiliation: Department of Medical Genetics, Faculty of Medical Sciences, University of Campinas (UNICAMP), 13083-887 Campinas, SP, Brazil.
authors.forename: Milena
authors.initials: M
authors.lastname: Simioni
authors.affiliation: Laboratory of Human and Medical Genetics, Institute of Biological Sciences, Federal University of Pará, Belém, 66.075-970 PA, Brazil.
authors.forename: Ândrea Kely Campos
authors.initials: ÂK
authors.lastname: Ribeiro-dos-Santos
authors.affiliation: Laboratory of Human and Medical Genetics, Institute of Biological Sciences, Federal University of Pará, Belém, 66.075-970 PA, Brazil.
authors.forename: Sidney Emanuel Batista
authors.initials: SE
authors.lastname: dos Santos
authors.affiliation: Department of Medical Genetics, Faculty of Medical Sciences, University of Campinas (UNICAMP), 13083-887 Campinas, SP, Brazil. Electronic address: vlopes@fcm.unicamp.br.
authors.forename: Vera Lúcia
authors.initials: VL
authors.lastname: Gil-da-Silva-Lopes
mesh_terms: D001938:Brazil; D016022:Case-Control Studies; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D000075065:Elongin; D005260:Female; D006801:Humans; D016547:Kinesins / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics
chemical_list: C000616397:ELOA protein, human; D000075065:Elongin; C502069:KIF7 protein, human; D014157:Transcription Factors; D016547:Kinesins
keywords: Case-control association study; KIF7; Nonsyndromic cleft lip and cleft palate; Single nucleotide polymorphism; TCEB3