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 t o play a role in the prevention of nonsyndromic orofacial cleft, i.e., clef t lip with or without cleft palate (CL/P). Moreover, some authors demonstra ted association of the C-T mutation (C677T), converting an alanine to a val ine residue in 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, with other congenital anomalies such as neural tube defects (NTDs), Because of M THFR's involvement in the metabolism of folate, we investigated 64 CLIP pat ients and their parents for C677T MTHFR mutation. No linkage disequilibrium was found using the transmission disequilibrium test (TDT), However, a sig nificantly higher mutation frequency was detected in mothers of CLIP patien ts compared to controls. The odds ratios calculated for mothers having CT o r TT genotype, compared to the normal CC genotype, were 2.75 (95% confidenc e interval ;1.30-5.57) and 2.51 (1.00-6.14), respectively. These results su pport the involvement of the folate pathway in the etiology of CLIP, and in dicate an effect of the maternal genotype, rather than influence of the emb ryo's genotype. (C) 2001 Wiley-Liss, Inc.