C677T variant form at the MTHFR gene and CL/P: a risk factor for mothers?
Maternal folic acid supplementation in early pregnancy has been suggested to play a role in the prevention of nonsyndromic orofacial cleft, i.e., cleft lip with or without cleft palate (CL/P). Moreover, some authors demonstrated association of the C-->T mutation (C677T), converting an alanine to a valine residue in 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, with other congenital anomalies such as neural tube defects (NTDs). Because of MTHFR's involvement in the metabolism of folate, we investigated 64 CL/P patients and their parents for C677T MTHFR mutation. No linkage disequilibrium was found using the transmission disequilibrium test (TDT). However, a significantly higher mutation frequency was detected in mothers of CL/P patients compared to controls. The odds ratios calculated for mothers having CT or TT genotype, compared to the normal CC genotype, were 2.75 (95% confidence interval 1.30-5.57) and 2.51 (1.00-6.14), respectively. These results support the involvement of the folate pathway in the etiology of CL/P, and indicate an effect of the maternal genotype, rather than influence of the embryo's genotype.
Martinelli
M
M
Department of Morphology and Embryology, Section of Histology and Embryology, University of Ferrara, Via Fossato di Mortara 64/B, 44100 Ferrara, Italy.
Scapoli
L
L
Pezzetti
F
F
Carinci
F
F
Carinci
P
P
Stabellini
G
G
Bisceglia
L
L
Gombos
F
F
Tognon
M
M
D000483:Alleles; D019943:Amino Acid Substitution; D002971:Cleft Lip / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002972:Cleft Palate / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D004247:DNA / Q000235:genetics; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D009154:Mutation; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*
D004247:DNA; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)