Possible effect of SNAIL family transcriptional repressor 1 polymorphisms in non-syndromic cleft lip with or without cleft palate
Orofacial development is a complex process subjected to failure impairing. Indeed, the cleft of the lip and/or of the palate is among the most frequent inborn malformations. The JARID2 gene has been suggested to be involved in non-syndromic cleft lip with or without cleft palate (nsCL/P) etiology. JARID2 interacts with the polycomb repressive complex 2 (PRC2) in regulating the expression patterns of developmental genes by modifying the chromatin state.
Materials and methods
Genes coding for the PRC2 components, as well as other genes active in cell differentiation and embryonic development, were selected for a family-based association study to verify their involvement in nsCL/P. A total of 632 families from Italy and Asia participated to the study.
Evidence of allelic association was found with polymorphisms of SNAI1; in particular, the rs16995010-G allele was undertransmitted to the nsCL/P cases [P = 0.004, odds ratio = 0.69 (95% C.I. 0.54–0.89)]. However, the adjusted significance value corrected for all the performed tests was P = 0.051.
The findings emerging by the present study suggest for the first time an involvement of SNAI1 in the nsCL/P onset.
Interestingly, SNAI1 is known to promote epithelial to mesenchymal transition by repressing E-cadherin expression, but it needs an intact PRC2 to act this function. Alterations of this process could contribute to the complex etiology of nsCL/P.
KeywordsAssociation study Epithelial to mesenchymal transition Non-syndromic cleft lip with or without cleft palate Polycomb repressive complex 2 Polymorphism SNAI1
We are indebted to the families participating in the study for their invaluable contribution, as well as to all the personnel involved in clinical data and specimen collection.
This work was supported in part by a grant from the Association Interethnos Interplast Italy and by Fondazione Del Monte di Bologna e Ravenna (for the salary of Dr. Ambra Girardi).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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