Prevalence of common mutations of the MTHFR gene in a Puerto Rican population

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate to methionine Fourteen severe mutations of the MTHFR gene have been found to result in only a 0-20 percent activity of the control MTHFR protein (Goyette, 1995). A common mutation (C677T), which results in high homocysteine and low plasma folate levels, has been associated with a thermolabile form of the MTHFR enzyme, therefore being a risk factor for cardiovascular diseases and neural tube defects (NTD) in the homozygous form (Frosst, 1995). Another mutation in the human MTHFR gene (A1298C) has been found to destroy an MboII recognition site and results in decreased MTHFR activity. Plasma and homocysteine levels are not altered with the A1298C mutation, however this mutation seems to be a risk factor when combined with the C677T mutation (Van der Put NM, 1998). In a prevalence study of the common C677T mutation screening in healthy women and newborn samples was performed we found that 8.6% of the individuals where homozygous for the mutation. These results compare with those found for Ohio Caucasian and Dublin populations (McAndrew, Kirke; 1996). Thirty NTD affected and control families were also analyzed in our laboratory for the C677T and A1298C mutations. Analysis of the A1298C mutation in 51 and 62 individuals from the control and NTD affected families, respectively, resulted in 8 control and 0 NTD affected individuals homozygous for the mutation. Taken together, the results of this study indicates that the Puerto Rican population has a low frecuency of the C677T mutation and confirms that homozygocity for the A1298C mutation does not present a direct risk for NTD. Supported by an RCMI Clinical Research Infrastructure Initiative (RCRII) Award IP20RR11126, National Center for Research Resources, RCMI Human Molecular Genetics Unit, NCRR-NIH RCMI Grant G12RR03051, and the Hereditary Disease Program, Department of Pediatrics, UPR, School of Medicine.