A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?
| Komentáře: | Comment in: Am J Hum Genet. 2000 Feb;66(2):744-5. (PMID: 10677336) |
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| Substance Nomenclature: | 0LVT1QZ0BA (Homocysteine) 8J337D1HZY (Cytosine) EC 1.5.- (Oxidoreductases Acting on CH-NH Group Donors) EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2)) JAC85A2161 (Adenine) KV2JZ1BI6Z (Pyridoxine) P6YC3EG204 (Vitamin B 12) |
| Entry Date(s): | Date Created: 19980523 Date Completed: 19980521 Latest Revision: 20220331 |
| Update Code: | 20240829 |
| PubMed Central ID: | PMC1377082 |
| DOI: | 10.1086/301825 |
| PMID: | 9545395 |
| Autor: | van der Put NM; Department of Pediatrics, University Hospital Nijmegen, Nijmegen, The Netherlands., Gabreëls F, Stevens EM, Smeitink JA, Trijbels FJ, Eskes TK, van den Heuvel LP, Blom HJ |
| Jazyk: | angličtina |
| Zdroj: | American journal of human genetics [Am J Hum Genet] 1998 May; Vol. 62 (5), pp. 1044-51. |
| DOI: | 10.1086/301825 |
| Abstrakt: | Recently, we showed that homozygosity for the common 677(C-->T) mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, causing thermolability of the enzyme, is a risk factor for neural-tube defects (NTDs). We now report on another mutation in the same gene, the 1298(A-->C) mutation, which changes a glutamate into an alanine residue. This mutation destroys an MboII recognition site and has an allele frequency of .33. This 1298(A-->C) mutation results in decreased MTHFR activity (one-way analysis of variance [ANOVA] P < .0001), which is more pronounced in the homozygous than heterozygous state. Neither the homozygous nor the heterozygous state is associated with higher plasma homocysteine (Hcy) or a lower plasma folate concentration-phenomena that are evident with homozygosity for the 677(C-->T) mutation. However, there appears to be an interaction between these two common mutations. When compared with heterozygosity for either the 677(C-->T) or 1298(A-->C) mutations, the combined heterozygosity for the 1298(A-->C) and 677(C-->T) mutations was associated with reduced MTHFR specific activity (ANOVA P < .0001), higher Hcy, and decreased plasma folate levels (ANOVA P <.03). Thus, combined heterozygosity for both MTHFR mutations results in similar features as observed in homozygotes for the 677(C-->T) mutation. This combined heterozygosity was observed in 28% (n =86) of the NTD patients compared with 20% (n =403) among controls, resulting in an odds ratio of 2.04 (95% confidence interval: .9-4.7). These data suggest that the combined heterozygosity for the two MTHFR common mutations accounts for a proportion of folate-related NTDs, which is not explained by homozygosity for the 677(C-->T) mutation, and can be an additional genetic risk factor for NTDs. |
| Databáze: | MEDLINE |
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