title: RFC1 and non-syndromic cleft lip with or without cleft palate: an association based study in Italy.
abstract: The molecular basis of orofacial development is largely unknown and needs to be unravelled. Non-syndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial malformation, with an incidence of about 1/700 live births, although variable according to ethnicity. Being a multifactorial disease, it arises as a result of an interplay between genetic and environmental factors. Several approaches have been developed to identify susceptibility genes. Genes belonging to the folate/homocysteine pathway are attracting increasing interest because folate supplementation before and during early pregnancy can reduce the risk of NSCL/P. We performed a family based association study in order to assess if a genetic variant of RFC1 could be involved in NSCL/P onset. We genotyped 404 unrelated probands and their relatives for three biallelic polymorphic variants (rs1051266, rs4818789 and rs3788205), that were selected because they produced conflicting results on previous investigations. Evidence of association was found between the investigated polymorphisms and NSCL/P in our sample of the Italian population, albeit with weak significance levels. Results from this investigation provided a support of previous studies suggesting a role of RFC1 in NSCL/P aetiology, reinforcing the concept that genetic predisposition to NSCL/P varies enormously within different ethnic groups.
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University di Bologna, Via Belmeloro 8, 40126 Bologna, Italy.
authors.forename: Ambra
authors.initials: A
authors.lastname: Girardi
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University di Bologna, Via Belmeloro 8, 40126 Bologna, Italy. Electronic address: marcella.martinelli@unibo.it.
authors.forename: Marcella
authors.initials: M
authors.lastname: Martinelli
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University di Bologna, Via Belmeloro 8, 40126 Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cura
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University di Bologna, Via Belmeloro 8, 40126 Bologna, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Palmieri
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Via Luigi Borsari 46, 44121 Ferrara, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Carinci
authors.affiliation: Head and Neck Department, University Hospital of Parma, Via Gramsci 14, 43100 Parma, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Sesenna
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University di Bologna, Via Belmeloro 8, 40126 Bologna, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Scapoli
mesh_terms: D002874:Chromosome Mapping; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007438:Introns / Q000235:genetics; D007558:Italy; D015810:Linkage Disequilibrium / Q000235:genetics; D020125:Mutation, Missense / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D051818:Replication Protein C / Q000235:genetics*
chemical_list: D005819:Genetic Markers; C081632:RFC1 protein, human; D051818:Replication Protein C
keywords: Association study; Cleft lip with or without cleft palate; Polymorphism; RFC1