title: Evidence of LEF1 fetal-maternal interaction in cleft lip with or without cleft palate in a consistent Italian sample study.
abstract: Epithelial mesenchymal transformation is considered a cardinal process in orofacial development. Several molecular players appear to be involved in this delicate mechanism; the activation of LEF1 transcription factor by transforming growth factor beta 3 seems to be a key step for the correct flow of events. The failure of orofacial processes during embryonic development may provoke cleft lip and/or cleft palate malformations. The scope of the present investigation was to verify whether genetic variants at LEF1 could influence the risk of orofacial clefting. The approach was a family based association study involving a total of 512 Italian patients and their parents, 401 having cleft lip with or without cleft palate (CL/P) and 111 with cleft palate only (CPO). Haplotype association analysis provided moderate evidence of an association with clefting (p 0.01). A log-linear likelihood-based method was used to verify maternal and foetal-maternal association. An association between the maternal genotype and the occurrence of CL/P was observed at two polymorphic loci, at rs10022956 (P = 0.0049) and rs10025431 (P = 0.0065) respectively, while a foetal-maternal effect modulating the risk of clefting was found at locus rs10025431 (P = 0.0071). These data further corroborate the importance of the mother's genotype with regard to susceptibility to malformations and early-onset diseases.
authors.affiliation: Department of Histology, Embryology and Applied Biology, Centre of Molecular Genetics, CARISBO Foundation, University of Bologna, Bologna, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Martinelli
authors.forename: F
authors.initials: F
authors.lastname: Carinci
authors.forename: P G
authors.initials: PG
authors.lastname: Morselli
authors.forename: E
authors.initials: E
authors.lastname: Caramelli
authors.forename: A
authors.initials: A
authors.lastname: Palmieri
authors.forename: A
authors.initials: A
authors.lastname: Girardi
authors.forename: C
authors.initials: C
authors.lastname: Riberti
authors.forename: L
authors.initials: L
authors.lastname: Scapoli
mesh_terms: D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007558:Italy; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D044465:White People / Q000235:genetics
chemical_list: C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1