Evidence of LEF1 fetal-maternal interaction in cleft lip with or without cleft palate in a consistent Italian sample study

• Published in: International journal of immunopathology and pharmacology Vol. 24; no. 2 Suppl; p. 15
• Main Authors: Martinelli, M, Carinci, F, Morselli, P G, Caramelli, E, Palmieri, A, Girardi, A, Riberti, C, Scapoli, L
• Format: Journal Article
• Language: English
• Published: England 01-04-2011
• Subjects: Cleft Lip - genetics; Cleft Palate - genetics; European Continental Ancestry Group - genetics; Female; Genotype; Humans; Italy; Lymphoid Enhancer-Binding Factor 1 - genetics; Polymorphism, Single Nucleotide; Pregnancy; Italy
• ISSN: 0394-6320
• DOI: 10.1177/03946320110240S204

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.