title: Maternal MTR genotype contributes to the risk of non-syndromic cleft lip and palate in the Polish population.
abstract: The aetiology of non-syndromic cleft lip with or without cleft palate (CL/P) is very complex. It has been shown that polymorphic variants of genes encoding key proteins of folate and methionine metabolism might be important maternal risk factors of having a child with this craniofacial anomaly. Therefore, in our study, mothers with CL/P children as well as control mothers were examined for prevalence of polymorphisms of genes that encode methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase (MTHFD1) and reduced folate carrier 1 (RFC1). We observed that there were no statistical differences in allele and genotype frequencies of MTHFR c.677C>T, MTHFD1 c.1958G>A and RFC1 c.80G>A between mothers who had children with CL/P and control mothers. However, mothers with MTR c.2756AG or GG genotype displayed a 2.195-fold increased risk of having a child with CL/P (95% CI 1.189-4.050, p = 0.011). The mechanism by which polymorphic transition of MTR gene might increase the maternal risk of having CL/P progeny is unknown. Our observations are consistent with a significant role of the methyl cycle in the development of craniofacial structures in humans.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Medical Sciences in Poznan, Poznan, Poland. amostowska@wp.pl
authors.forename: A
authors.initials: A
authors.lastname: Mostowska
authors.forename: K K
authors.initials: KK
authors.lastname: Hozyasz
authors.forename: P P
authors.initials: PP
authors.lastname: Jagodzinski
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000328:Adult; D002971:Cleft Lip / Q000201:enzymology* / Q000235:genetics*; D002972:Cleft Palate / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D009035:Mothers; D017354:Point Mutation; D011044:Poland; D012307:Risk Factors
chemical_list: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase