title: Evaluating SKI as a candidate gene for non-syndromic cleft lip with or without cleft palate.
abstract: Non-syndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common of all congenital malformations and has a multifactorial etiology. Findings in mice suggest that the v-ski sarcoma viral oncogene homolog (SKI) gene is a candidate gene for orofacial clefting. In humans, a significant association between rs2843159 within SKI and NSCL/P has been reported in patients from the Philippines and South America. In the South American patients, the association was driven by the subgroup of patients with non-syndromic cleft lip only (NSCLO). Here we investigated the association with rs2843159 in a Mayan Mesoamerican population (172 NSCL/P patients and 366 controls). In addition, we analyzed the phenotypic subgroups NSCLO and non-syndromic cleft of lip and palate (NSCLP). A trend towards association between rs2843159 and NSCL/P was observed in the Mayan cohort (P = 0.097), and we found a stronger association in the NSCLP subgroup (P = 0.072) despite a limited sample size. To investigate whether other common variants within the SKI gene contribute to NSCL/P susceptibility in European and Asian populations, we also analyzed genotypic data from two recent genome-wide association studies using set-based statistical approaches. These analyses detected a trend toward association in the European population. Our data provide limited support for the hypothesis that common SKI variants are susceptibility factors for NSCL/P.
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mangold
authors.forename: Heiko
authors.initials: H
authors.lastname: Reutter
authors.forename: Rafael B R
authors.initials: RB
authors.lastname: León-Cachón
authors.forename: Kerstin U
authors.initials: KU
authors.lastname: Ludwig
authors.forename: Stefan
authors.initials: S
authors.lastname: Herms
authors.forename: Óscar
authors.initials: Ó
authors.lastname: Chacón-Camacho
authors.forename: Rocío
authors.initials: R
authors.lastname: Ortiz-López
authors.forename: Mario
authors.initials: M
authors.lastname: Paredes-Zenteno
authors.forename: Abelardo
authors.initials: A
authors.lastname: Arizpe-Cantú
authors.forename: Sergio G
authors.initials: SG
authors.lastname: Muñoz-Jiménez
authors.forename: Stefanie
authors.initials: S
authors.lastname: Nowak
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Kramer
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Wienker
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Michael
authors.initials: M
authors.lastname: Knapp
authors.forename: Augusto
authors.initials: A
authors.lastname: Rojas-Martínez
mesh_terms: D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008297:Male; D008800:Mexico; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C060614:SKI protein, human