scholarly journals The impact of Folate Pathway Polymorphisms Combined to Nutritional Deficiency As a Maternal Predisposition Factor for Down Syndrome

2008 ◽  
Vol 25 (3) ◽  
pp. 149-157 ◽  
Author(s):  
C. B. Santos-Rebouças ◽  
J. C. Corrêa ◽  
A. Bonomo ◽  
N. Fintelman-Rodrigues ◽  
K. C. V. Moura ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Methylenetetrahydrofolate Reductase ◽  
Genetic Profile ◽  
Negative Effects ◽  
Methionine Synthase Reductase ◽  
Genotype Frequencies ◽  
Folate Pathway ◽  
Increased Risk ◽  
Reductase Gene ◽  
The Impact

Polymorphisms in genes encoding folate metabolizing enzymes have been linked to an increased risk of maternal chromosomal nondisjunction in several populations. With the purpose of evaluating this relationship, we compared the frequencies of 677C>T and 1298A>C polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) and 66A>G in the methionine synthase reductase gene (MTRR) between 103 young mothers of Down syndrome (DS) individuals and 108 control mothers, whose offspring was karyotypically normal, correlating it with an estimative of folate and – related micronutrients levels intake. Maternal and paternal transmission frequencies ofMTHFR677T allele were also examined to access potential parent-of-origin effects. PCR-RFLP for genomic DNA was accomplished and allele/genotype frequencies differences were determined using the x2test, whereas pattern of transmission of theMTHFR677 allele was analyzed by transmission disequilibrium test. None of the polymorphisms seemed to be more frequent in case mothers than in controls, either individually or combined. The estimative of nutritional intake revealed that folate consumption median was inadequate in both groups, whereas methionine and zinc consumption medians were significantly greater in control mothers. It suggests that such interaction between genetic profile and environment could predispose this sub group of women to have a DS child. Additional studies focusing the interaction between nutritional intakes, biochemical data and folate pathway polymorphisms are needed to confirm the present results. The possibility of neutralize the biochemical negative effects of folate-related polymorphisms through oral supplementation could provide new targets for DS prevention.

scholarly journals Investigation of Homocysteine-Pathway-Related Variants in Essential Hypertension

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Javed Y. Fowdar ◽  
Marta V. Lason ◽  
Attila L. Szvetko ◽  
Rodney A. Lea ◽  
Lyn R. Griffiths
Keyword(s):  
Essential Hypertension ◽  
Methylenetetrahydrofolate Reductase ◽  
Interaction Model ◽  
Mthfr A1298c ◽  
Methionine Synthase Reductase ◽  
Pathway Gene ◽  
Mtrr A66g ◽  
Increased Risk ◽  
Reductase Gene ◽  
Chi Square Analysis

Hyperhomocysteinemia (hHcy) has been associated with an increased risk of cardiovascular disease and stroke. Essential hypertension (EH), a polygenic condition, has also been associated with increased risk of cardiovascular related disorders. To investigate the role of the homocysteine (Hcy) metabolism pathway in hypertension we conducted a case-control association study of Hcy pathway gene variants in a cohort of Caucasian hypertensives and age- and sex-matched normotensives. We genotyped two polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR C677T and MTHFR A1298C), one polymorphism in the methionine synthase reductase gene (MTRR A66G), and one polymorphism in the methylenetetrahydrofolate dehydrogenase 1 gene (MTHFD1 G1958A) and assessed their association with hypertension using chi-square analysis. We also performed a multifactor dimensionality reduction (MDR) analysis to investigate any potential epistatic interactions among the four polymorphisms and EH. None of the four polymorphisms was significantly associated with EH and although we found a moderate synergistic interaction between MTHFR A1298C and MTRR A66G, the association of the interaction model with EH was not statistically significant (P=0.2367). Our findings therefore suggest no individual or interactive association between four prominent Hcy pathway markers and EH.

scholarly journals Functional Inference of Methylenetetrahydrofolate Reductase Gene Polymorphisms on Enzyme Stability as a Potential Risk Factor for Down Syndrome in Croatia

2010 ◽  
Vol 28 (5) ◽  
pp. 293-298 ◽  
Author(s):  
Jadranka Vraneković ◽  
Ivana Babić Božović ◽  
Nada Starčević Čizmarević ◽  
Alena Buretić-Tomljanović ◽  
Smiljana Ristić ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Methylenetetrahydrofolate Reductase ◽  
Enzyme Stability ◽  
Genotype Frequencies ◽  
Reductase Gene ◽  
Pcr Rflp ◽  
Functional Inference ◽  
The Stability ◽  
And Function ◽  
Methylenetetrahydrofolate Reductase Gene

Understanding the biochemical structure and function of the methylenetetrahydrofolate reductase gene (MTHFR) provides new evidence in elucidating the risk of having a child with Down syndrome (DS) in association with two commonMTHFRpolymorphisms, C677T and A1298C. The aim of this study was to evaluate the risk for DS according to the presence ofMTHFRC677T and A1298C polymorphisms as well as the stability of the enzyme configuration. This study included mothers from Croatia with a liveborn DS child (n= 102) or DS pregnancy (n= 9) and mothers with a healthy child (n= 141).MTHFRC677T and A1298C polymorphisms were assessed by PCR-RFLP. Allele/genotype frequencies differences were determined using χ2test. Odds ratio and the 95% confidence intervals were calculated to evaluate the effects of different alleles/genotypes. No statistically significant differences were found between the frequencies of allele/genotype or genotype combinations of theMTHFRC677T and A1298C polymorphisms in the case and the control groups. Additionally, the observed frequencies of the stable (677CC/1298AA, 677CC/1298AC, 677CC/1298CC) and unstable (677CT/1298AA, 677CT/1298AC, 677TT/1298AA) enzyme configurations were not significantly different. We found no evidence to support the possibility thatMTHFRpolymorphisms and the stability of the enzyme configurations were associated with risk of having a child with DS in Croatian population.

scholarly journals Haplotype analysis of the folate-related genes MTHFR, MTRR, and MTR and migraine with aura

Cephalalgia ◽  
2013 ◽  
Vol 33 (7) ◽  
pp. 469-482 ◽  
Author(s):  
Kathryn A Roecklein ◽  
Ann I Scher ◽  
Albert Smith ◽  
Tamara Harris ◽  
Gudny Eiriksdottir ◽  
...  
Keyword(s):  
Migraine With Aura ◽  
Multiple Testing ◽  
Haplotype Analysis ◽  
Methylenetetrahydrofolate Reductase ◽  
Population Based ◽  
Methionine Synthase ◽  
Association Testing ◽  
Methionine Synthase Reductase ◽  
Increased Risk ◽  
Genes Encoding

Aims The C677T variant in the methylenetetrahydrofolate reductase ( MTHFR; EC 1.5.1.20) enzyme, a key player in the folate metabolic pathway, has been associated with increased risk of migraine with aura. Other genes encoding molecular components of this pathway include methionine synthase ( MTR; EC 2.1.1.13) and methionine synthase reductase ( MTRR; EC 2.1.1.135) among others. We performed a haplotype analysis of migraine risk and MTHFR, MTR, and MTRR. Methods Study participants are from a random sub-sample participating in the population-based AGES-Reykjavik Study, including subjects with non-migraine headache ( n = 367), migraine without aura ( n = 85), migraine with aura ( n = 167), and no headache ( n = 1347). Haplotypes spanning each gene were constructed using Haploview. Association testing was performed on single SNP and haplotypes using logistic regression, controlling for demographic and cardiovascular risk factors and correcting for multiple testing. Results Haplotype analysis suggested an association between MTRR haplotypes and reduced risk of migraine with aura. All other associations were not significant after correcting for multiple testing. Conclusions These results suggest that MTRR variants may protect against migraine with aura in an older population.

Genetic Polymorphisms in the Folate Pathway and Risk of Childhood Acute Lymphoblastic Leukemia (ALL): MTHFR, MTHFD1, RFC1 and TS.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2274-2274
Author(s):  
Allen Eng-Juh Yeoh ◽  
Shirley Kow-Yin Kham ◽  
Yi Lu ◽  
Toon-Chai Foo ◽  
Hany Ariffin ◽  
...  
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Lymphoblastic Leukemia ◽  
In Utero ◽  
Folate Metabolism ◽  
Childhood Leukaemia ◽  
Wild Type ◽  
Nucleotide Synthesis ◽  
Childhood All ◽  
Folate Pathway ◽  
The Impact

Abstract Folate is critical for DNA synthesis and methylation; dysfunction in methylating enzymes may result in genomic instability and DNA damage via the nucleotide synthesis pathways. We hypothesize that perturbation in the folate metabolism pathway may alter the risk of developing childhood leukaemia. We recently reported that methylenetetrahydrofolate reductase (MTHFR 677C>T) was associated with reduced risk in childhood ALL. We aim to explore the value of a pathway approach, in this case exploring the impact of polymorphisms in multiple enzymes involved in the folate pathway, to determine its role in development of childhood ALL. As childhood ALL is highly heterogeneous and that some like TEL-AML1 and hyperdiploid subgroups have in utero origin, we postulated that the impact of folate metabolism may be greatest for in utero onset ALL. We analyzed the methylenetetrahydrofolate dehydrogenase (MTHFD1), reduced folate carrier (RFC1) and thymidylate synthase (TSER 5′-UTR 28bp repeat, TSER 3′-UTR 6bp deletion) in 360 children with ALL and 433 controls of Chinese and Malay origin (Ch=221, Mal=212). Genotyping was performed by RFLP-PCR, TEL-AML1 by RT-PCR, and hyperdiploidy either DNA index (≥1.16) or karyotyping. The latter was only available in some patients, especially in the Chinese. Using logistic regression model analysis, MTHFR 677C>T and MTHFD1 1958G>A showed significant influence on leukemia susceptibility in the Chinese (n=235, p=0.005) and Malays (n=125, p=0.032) respectively. In the Chinese cohort, MTHFR 677 CT and TT genotypes significantly decreased risk of childhood ALL as compared to CC wild type (p=0.004, OR=0.57, 95%CI=0.39–0.83), as well as in the hyperdiploidy subgroup (n=35, p=0.002, OR=0.28, 95%CI=0.12–0.65). The combined effect of RFC 80GA and AA genotypes with MTHFR 677CC wild type also decreased risk of childhood ALL in Chinese (p=0.05, OR=0.47, 95%CI=0.22–1.0). In the Malay cohort, the MTHFR 677 CT and TT genotypes played a protective role only in the TEL-AML1 subgroup (n=27) as compared to CC wild type (p=0.05, OR=0.24, 95%CI=0.06–1.0). However, interestingly MTHFD1 1958GG wild type decreased risk of childhood ALL as compared to MTHFD1 1958GA or AA genotypes (p=0.02, OR=0.54, 95%CI=1.11–3.05) when combined with MTHFR 677CC genotype. Haplotype analysis of TSER variants showed no significant effect in the 2 races. Using a candidate pathway approach, we showed that polymorphisms in the folate pathway significantly modified the risk of developing childhood ALL especially the MTHFR, MTHFD1 and RFC1. This effect may arise from different genes of the same pathway and this may be different for different races. This supports a pathway way rather than a single-gene approach towards elucidation of cancer risk in childhood ALL.

scholarly journals Impact of television on children and adolescents: A research review

2016 ◽  
pp. 917-929
Author(s):  
Ana Pesikan
Keyword(s):  
Children And Adolescents ◽  
Dietary Habits ◽  
Violent Behavior ◽  
Research Review ◽  
Negative Effects ◽  
Beneficial Effects ◽  
Positive Effects ◽  
Increased Risk ◽  
Elevated Cholesterol ◽  
The Impact

Media has one of the most important and under-recognized influence on health, development and behavior of children and adolescents. Television is still the most popular form of media among children and adolescents. In the last 50 years, more than a thousand researches have been carried out in the world showing the great impact of television on children and adolescents. Television shapes the attitudes, beliefs and behaviors of children and adolescents and strongly influences their perception of reality. The high impact of television is neither recognized by children nor adults; they estimate that the media affect all others except themselves. Television can positively influence a child?s prosocial behavior and acquisition of certain types of knowledge. However, the positive effects have been much less common and usually obtained at a younger age (3-5 years). Most of the studies provide a persistent and robust findings indicating the correlation between exposure to television and a variety of health problems (such as obesity, low physical activity, elevated cholesterol, diabetes, high blood pressure, etc.) and an increased risk of certain types of behavior (like poor dietary habits, less sleep, smoking, violent behavior, alcoholism, drug addiction, etc.). The research results show that the potentials of television with beneficial effects on children have not been realized; the list of negative effects is much longer and much more diverse; and strategies to reduce the negative effects of television do not apply. The documented findings on the impact of television should elicit serious concern, not just from parents and educators but from many others such as physicians, public health advocates, entertainment industry, politicians, and government.

scholarly journals Impact of the common MTHFR 677C→T polymorphism on blood pressure in adulthood and role of riboflavin in modifying the genetic risk of hypertension: evidence from the JINGO project

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Mary Ward ◽  
Catherine F. Hughes ◽  
J. J. Strain ◽  
Rosie Reilly ◽  
Conal Cunningham ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Genetic Risk ◽  
Antihypertensive Treatment ◽  
Methylenetetrahydrofolate Reductase ◽  
Randomised Trial ◽  
Population Based ◽  
Nutrition Survey ◽  
Increased Risk ◽  
The Impact ◽  
Riboflavin Status

Abstract Background Genome-wide and clinical studies have linked the 677C→T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) with hypertension, whilst limited evidence shows that intervention with riboflavin (i.e. the MTHFR co-factor) can lower blood pressure (BP) in hypertensive patients with the variant MTHFR 677TT genotype. We investigated the impact of this common polymorphism on BP throughout adulthood and hypothesised that riboflavin status would modulate the genetic risk of hypertension. Methods Observational data on 6076 adults of 18–102 years were drawn from the Joint Irish Nutrigenomics Organisation project, comprising the Trinity-Ulster Department of Agriculture (TUDA; volunteer sample) and the National Adult Nutrition Survey (NANS; population-based sample) cohorts. Participants were recruited from the Republic of Ireland and Northern Ireland (UK) in 2008–2012 using standardised methods. Results The variant MTHFR 677TT genotype was identified in 12% of adults. From 18 to 70 years, this genotype was associated with an increased risk of hypertension (i.e. systolic BP ≥ 140 and/or a diastolic BP ≥ 90 mmHg): odds ratio (OR) 1.42, 95% confidence interval (CI) 1.07 to 1.90; P = 0.016, after adjustment for antihypertensive drug use and other significant factors, namely, age, male sex, BMI, alcohol and total cholesterol. Low or deficient biomarker status of riboflavin (observed in 30.2% and 30.0% of participants, respectively) exacerbated the genetic risk of hypertension, with a 3-fold increased risk for the TT genotype in combination with deficient riboflavin status (OR 3.00, 95% CI, 1.34–6.68; P = 0.007) relative to the CC genotype combined with normal riboflavin status. Up to 65 years, we observed poorer BP control rates on antihypertensive treatment in participants with the TT genotype (30%) compared to those without this variant, CT (37%) and CC (45%) genotypes (P < 0.027). Conclusions The MTHFR 677TT genotype is associated with higher BP independently of homocysteine and predisposes adults to an increased risk of hypertension and poorer BP control with antihypertensive treatment, whilst better riboflavin status is associated with a reduced genetic risk. Riboflavin intervention may thus offer a personalised approach to prevent the onset of hypertension in adults with the TT genotype; however, this requires confirmation in a randomised trial in non-hypertensive adults.

Polymorphisms and haplotypes in folate-metabolizing genes and risk of non-Hodgkin lymphoma

Blood ◽  
2004 ◽  
Vol 104 (7) ◽  
pp. 2155-2162 ◽  
Author(s):  
Christine F. Skibola ◽  
Matthew S. Forrest ◽  
Fabio Coppedé ◽  
Luz Agana ◽  
Alan Hubbard ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Genetic Polymorphisms ◽  
San Francisco ◽  
Methylenetetrahydrofolate Reductase ◽  
Large Cell ◽  
Population Based ◽  
Folate Metabolism ◽  
Non Hodgkin Lymphoma ◽  
Genotype Frequencies ◽  
Increased Risk

Abstract Folate metabolism plays an essential role in DNA synthesis and methylation processes. Deviations in the flux of folate due to genetic variation could result in selective growth and genomic instability and affect susceptibility to various cancers including lymphoma. To test this hypothesis, genetic polymorphisms in the folate metabolic pathway were investigated using DNA from a population-based case-control study of non-Hodgkin lymphoma (NHL) conducted in the San Francisco Bay Area between 1988 and 1995. The polymorphisms examined and haplotypes generated included thymidylate synthase (TYMS 28-bp triple repeat [3R] → double repeat [2R], 1494del6, IVS6 -68C&gt;T, 1122A&gt;G, and 1053C&gt;T); 5,10-methylenetetrahydrofolate reductase (MTHFR 677C&gt;T and 1298A&gt;C); serine hydroxymethyltransferase (SHMT1 C1420T); reduced folate carrier (RFC G80A); and methionine synthase (MTR A2756G), making the present study the largest and most comprehensive to date to evaluate associations between genetic polymorphisms in folatemetabolizing genes and NHL risk. The TYMS 6 base pair (bp)-6bp- (homozygous for 6bp deletion), IVS6 -68C&gt;T, and 1053C&gt;T genotypes (all in complete linkage disequilibrium) were all inversely associated with NHL (TYMS; odds ratio [OR] = 0.57; 0.34-0.94), particularly with diffuse large cell lymphoma (DLCL; OR = 0.29; 0.10-0.82). Further, the MTR 2756AG/GG and the MTHFR 677TT genotypes were associated with increased risk for NHL (OR = 1.3; 0.99-1.7) and follicular lymphoma (FL; OR = 1.8; 0.98-3.1), respectively. We did not observe any significant differences in genotype frequencies of the SHMT1 and RFC polymorphisms between the cases and controls. The associations of DLCL and FL with TYMS 1494del6 and MTHFR 677TT genotypes, respectively, suggest that folate metabolism may play an important role in the pathogenesis of specific subtypes of NHL. (Blood. 2004;104: 2155-2162)

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