title: Evidence of the involvement of the DHFR gene in nonsyndromic cleft lip with or without cleft palate.
abstract: Studies aimed at evidencing genetic causes for neural tube defect (NTD) occurrence have often provided the inspiration for orofacial cleft aetiology investigations. The correlation between the two congenital malformations is provided by the similar incidence timing and the involvement of structures localized in the midline of the embryo. This connection is corroborated by the existence of a number of genes involved in both malformations. In this article, we considered the dihydrofolate reductase (DHFR) gene, previously seen implicated in NTDs, as a candidate for cleft lip with or without cleft palate (CL/P) risk. Four SNPs mapping on the DHFR gene were genotyped for 400 Italian CL/P triads, using TaqMan(®) approach. The rs1677693 provided evidence of association, even if at borderline level (P value 0.049). In particular, the variant allele seems to have a protective effect OR = 0.80 (95% C.I. 0.64-0.99). Moreover, the combination of rs1677693(A)-rs1650723(G) alleles showed a significant association OR 0.64 (95% C.I. 0.47-0.86) (P value = 0.006). This represents the first attempt to demonstrate a role for DHFR in CL/P aetiology, howbeit the study of such gene deserves a deepening.
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: 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.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cura
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: Department of Experimental, Diagnostic and Specialty Medicine, University di Bologna, Via Belmeloro 8, 40126 Bologna, Italy.
authors.forename: Paolo Giovanni
authors.initials: PG
authors.lastname: Morselli
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: D016022:Case-Control Studies; D002971:Cleft Lip / Q000201:enzymology / Q000235:genetics*; D002972:Cleft Palate / Q000201:enzymology / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D017422:Sequence Analysis, DNA; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
chemical_list: D013762:Tetrahydrofolate Dehydrogenase
keywords: Association; Cleft lip with or without cleft palate; DHFR; Polymorphism