Methylenetetrahydrofolate reductase thermolabile variant and oral clefts

Folic acid can prevent neural tube defects; in some cases the mechanism is probably a correction of a metabolic defect caused by thermolabile methylen etetrahydrofolate reductase (MTHFR) found in increased frequency in cases. It is less clear whether folic acid can prevent oral clefts, in part becaus e it is not known whether thermolabile MTHFR is more common in those with o ral clefts. This study examined the prevalence of the mutation (677 C-->T) that causes thermolabile MTHFR in subjects with oral clefts from a national Irish support group, and an anonymous control group randomly selected from a neonatal screening program covering all births in Ireland. Eighty-three of 848 control subjects were homozygous (TT) thermolabile MTHFR (9.8%). Thi s defect was almost three times as common in the 27 subjects (25.9%) with i solated cleft palate (odds ratio 3.23, 95% confidence interval 1.32 -7.86, P = 0.02) and somewhat more common in the 66 subjects with cleft lip with o r without cleft palate (15.2%, odds ratio 1.65, 95% confidence interval 0.8 1-3.35, P = 0.20). When the two groups with different etiologies were combi ned, the overall odds ratio was 2.06 (95% confidence interval 1.16-3.66, P = 0.02). In the Irish population homozygosity for the common folate-related polymorphism associated with thermolabile MTHFR is significantly more freq uent in those with isolated cleft palate, and could be etiologically import ant. Am. J, Med. Genet, 86:71-74, 1999, Published 1999 Wiley-Liss, Inc.dagg er