A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?

American Journal of Human Genetics
N M van der PutH J Blom

Abstract

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 mut...Continue Reading

References

Dec 24, 1992·The New England Journal of Medicine·A E Czeizel, I Dudás
Jan 1, 1990·Progress in Neurobiology·A J CoppD L Cockroft
Mar 1, 1995·Annals of Clinical Biochemistry·M T te Poele-PothoffH J Blom
Feb 1, 1997·QJM : Monthly Journal of the Association of Physicians·N M van der PutH J Blom
Aug 1, 1997·QJM : Monthly Journal of the Association of Physicians·N M van der PutH J Blom

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Citations

Jul 19, 2000·Mental Retardation and Developmental Disabilities Research Reviews·S M ManningJ R Madsen
Jun 22, 2000·Teratology·A C Antony, D K Hansen
Aug 9, 2001·International Journal of Cancer. Journal International Du Cancer·H ShenQ Wei
Aug 2, 2005·Bioelectromagnetics·Tracy Lightfoot
Jan 5, 2002·Genetic Epidemiology·Terri H BeatyI McIntosh
Aug 31, 2002·Human Mutation·Jan AertsJeroen Aerssens
Sep 7, 2002·Mental Retardation and Developmental Disabilities Research Reviews·Maureen Durkin
Apr 5, 2002·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Rowena G Matthews
Aug 2, 2008·Journal of Applied Genetics·Elisabetta Trabetti
Nov 28, 2008·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·K ZhuR L Prince
Mar 17, 2012·European Journal of Clinical Pharmacology·Tiphaine Adam de Beaumais, Evelyne Jacqz-Aigrain
Jan 15, 2013·Cancer Chemotherapy and Pharmacology·Kyung-Hun LeeTae-You Kim
Nov 18, 2006·International Journal of Colorectal Disease·Carmen S P LimaCarmen S Bertuzzo
Aug 12, 2009·International Journal of Colorectal Disease·Antonia M Fernández-PeraltaJuan J González-Aguilera
Feb 21, 2013·International Journal of Colorectal Disease·Luciano Delgado-PlasenciaJuan J González-Aguilera
Apr 25, 2012·European Journal of Nutrition·Mark LucockMartin Veysey
Feb 21, 2006·Journal of Human Genetics·Amit Kumar RaiRajiva Raman
Sep 27, 2012·Biochemical Genetics·Seerat SachdevaS L Malik
Jan 25, 2007·Cancer Causes & Control : CCC·Maureen A MurtaughMartha L Slattery
Mar 7, 2008·Cancer Causes & Control : CCC·Gwen MurphyElaine Lanza
Apr 15, 2006·Digestive Diseases and Sciences·Gabriele StoccoAlessandro Ventura
Mar 16, 2007·Documenta Ophthalmologica. Advances in Ophthalmology·Martin HeurElisa Bala
Nov 12, 2010·Journal of Autism and Developmental Disorders·Xudong LiuJeanette J A Holden
Oct 26, 2005·Journal of Assisted Reproduction and Genetics·Jung Hoon ParkSuman Lee
Apr 5, 2011·Journal of Community Health·Benrithung MurryK N Saraswathy
Jun 7, 2011·Molecular Biology Reports·Bingbing WeiZhirong Wang

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