Human genetic selection on the MTHFR 677C&gt;T polymorphism

Mayor-Olea, Álvaro; Callejón, Gonzalo; Palomares, Arturo Reyes; Jiménez, Ana José; Gaitán, María Jesús; Rodríguez, Alfonso; Ruiz, M.; Reyes‐Engel, Armando

doi:10.1186/1471-2350-9-104

Cited by 34 publications

(27 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The observed increase of the T-allelic frequency in the group of women in study, born in the last quarter of the last century, has been already associated with some selective advantage in a previous research conducted on a Spanish population (Mayor-Olea et al, 2008). Particularly, it has been reported that selection in favor of the T allele could be due to the increased fetal viability in early stages of embryonic development due to an increase in folic acid and vitamin supplements intake by women in the periconceptional period that began to be established in Spain in the last quarter of the 20th century as well as it started in other European countries including Italy (MayorOlea et al, 2008).…”

Section: Discussionmentioning

confidence: 90%

Increase in the prevalence of the MTHFR 677 TT polymorphism in women born since 1959: potential implications for folate requirements

et al. 2011

View full text Add to dashboard Cite

Background/Objectives: Folate has been recognized to ensure reproductive health and there is a growing body of epidemiological evidence suggesting that the methylenetetrahydrofolate reductase (MTHFR) 677T allele and reduced dietary folate may increase the risk of cervical cancer. The main focus of our survey was to investigate the distribution of the MTHFR C677T polymorphism in relation to women's year of birth and to assess their folate intake and folic acid supplementation. Subjects/Methods: During a 6-months period, 307 healthy women of childbearing age in Catania, Italy, were enrolled in the cross-sectional study. Folate intake was estimated by a semiquantitative food frequency questionnaire and DNA extracted from blood samples for MTHFR C677T genotyping. Results: A TT genotype frequency of 20.5% with an increase in the prevalence of the TT genotype in the cohort of women born since 1959 was shown. The prevalence of inadequate folate intake was 51.5%, significantly higher in non-pregnant women (83.4%) than in pregnant ones (12.3%) with a decrease during the three trimesters of pregnancy (from 25.7 to 5.0%; P ¼ 0.013). The use of folic acid supplements improved during the three trimester of pregnancy (from 71.4 to 95.0%; P ¼ 0.001).Conclusions: Healthy young women may have higher folate needs due to increasing prevalence of the T allele and reduced folate intake compared with older groups. However, clinicians should be cautious when recommending supplements to women in late pregnancy due to the possible implications in the pregnancy outcome.

show abstract

Section: Discussionmentioning

confidence: 90%

Increase in the prevalence of the MTHFR 677 TT polymorphism in women born since 1959: potential implications for folate requirements

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Por ello, las menores frecuencias alélicas de nuestro estudio (muestra reclutada durante 2010-2012), parecen paradójicas. Se ha postulado que el uso de acido fólico produciría una selección genética en favor de alelos asociados a una menor actividad de MTHFR (677T y 1298C) 11,12 . Por esta razón debiéramos esperar un aumento de la frecuencia de estos alelos con el paso del tiempo en la población general, resultado opuesto a lo observado en el presente estudio.…”

Section: Discussionunclassified

“…No obstante, se han descrito resultados controversiales respecto a la asociación de estas variantes con el riesgo de presentar DTN en varias poblaciones, inconsistencias que podrían ser explicadas por el diferente origen étnico de dichas muestras [8][9][10] . Se ha descrito además que el uso de acido fólico induciría una selección genética en favor de los alelos asociados a una menor actividad de MTHFR (677T y 1298C) 11,12 . Se ha comunicado sólo un estudio previo, publicado en 2003, enfocado en el rol de variantes de la MTHFR en la EB en Chile.…”

unclassified

Estudio de asociación de base familiar entre polimorfismos de MTHFR y mielomeningocele en Chile

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Indeed, chronic alcohol abuse is associated with an increased risk of a variety of cancers (6,19). Mthfr 677C3 T mutation, common in the human population and associated with increased OCM impairment, is known to increase the risk of alcohol-induced cancer (46,47). Thus, OCM impairment as a part of the mechanism involved in alcohol genotoxicity was mainly studied in the context of carcinogenesis (6,(17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%

“…Templates for qPCR-based BER activity assay genomic stability in the brain, we utilized MTHFR-deficient mice with heterozygous (ϩ/Ϫ) disruption of the gene that represents a mild MTHFR deficiency in humans with 677C3 T mutation in the gene encoding MTHFR and is common in human populations (46,47). The mice were phenotypically normal but more sensitive to conditions affecting OCM (e.g.…”

Section: Tablementioning

confidence: 99%

Alcohol-induced One-carbon Metabolism Impairment Promotes Dysfunction of DNA Base Excision Repair in Adult Brain

Fowler

Hewetson

Agrawal

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: DNA repair dysfunction leads to genomic instability and neuron death. Results: Long term alcohol exposure results in reduced DNA repair, increased DNA damage, and neuron death in adult brain. Conclusion: Long term alcohol exposure in adult brain promotes genomic instability mediated by impairment in one-carbon metabolism. Significance: This is the first demonstration of alcohol-induced genomic instability in brain.The brain is one of the major targets of chronic alcohol abuse. Yet the fundamental mechanisms underlying alcohol-mediated brain damage remain unclear. The products of alcohol metabolism cause DNA damage, which in conditions of DNA repair dysfunction leads to genomic instability and neural death. We propose that one-carbon metabolism (OCM) impairment associated with long term chronic ethanol intake is a key factor in ethanol-induced neurotoxicity, because OCM provides cells with DNA precursors for DNA repair and methyl groups for DNA methylation, both critical for genomic stability. Using histological (immunohistochemistry and stereological counting) and biochemical assays, we show that 3-week chronic exposure of adult mice to 5% ethanol (Lieber-Decarli diet) results in increased DNA damage, reduced DNA repair, and neuronal death in the brain. These were concomitant with compromised OCM, as evidenced by elevated homocysteine, a marker of OCM dysfunction. We conclude that OCM dysfunction plays a causal role in alcohol-induced genomic instability in the brain because OCM status determines the alcohol effect on DNA damage/repair and genomic stability. Short ethanol exposure, which did not disturb OCM, also did not affect the response to DNA damage, whereas additional OCM disturbance induced by deficiency in a key OCM enzyme, methylenetetrahydrofolate reductase (MTHFR) in Mthfr ؉/؊ mice, exaggerated the ethanol effect on DNA repair. Thus, the impact of long term ethanol exposure on DNA repair and genomic stability in the brain results from OCM dysfunction, and MTHFR mutations such as Mthfr 677C3 T, common in human population, may exaggerate the adverse effects of ethanol on the brain.Nearly 100 million people worldwide have alcohol use disorders. Brain damage is a common and potentially severe consequence of alcohol abuse (1). It is estimated that 50 -75% of long term alcoholics exhibit cognitive impairment and structural damage to the brain. It is also known that chronic alcohol abuse is associated with cerebral cortical atrophy (1). Neuropathological analyses have provided evidence for loss of neurons in certain brain regions such as frontal lobes, which are highly affected in the alcoholic brain (1, 2). This region is essential for executive functions, whose loss may lead to a progressive loss of these functions, as seen in people addicted to alcohol as well as in individuals with frontal cortical damage (2, 3). These structural and cognitive changes have been suggested as the primary consequence of alcohol toxicity (4).Alcohol consumption is associated with generation of genotoxic metabolit...

show abstract

Human genetic selection on the MTHFR 677C>T polymorphism

Cited by 34 publications

References 22 publications

Increase in the prevalence of the MTHFR 677 TT polymorphism in women born since 1959: potential implications for folate requirements

Increase in the prevalence of the MTHFR 677 TT polymorphism in women born since 1959: potential implications for folate requirements

Estudio de asociación de base familiar entre polimorfismos de MTHFR y mielomeningocele en Chile

Alcohol-induced One-carbon Metabolism Impairment Promotes Dysfunction of DNA Base Excision Repair in Adult Brain

Contact Info

Product

Resources

About