Association of total plasma homocysteine with methylenetetrahydrofolate reductase genotypes 677C&gt;T, 1298A&gt;C, and 1793G&gt;A and the corresponding haplotypes in Swedish children and adolescents

Böttiger, Anna K.; Hurtig-Wennlöf, Anita; Sjöstróm, Michael; Yngve, Agneta; Nilsson, Torbjörn

doi:10.3892/ijmm.19.4.659

Cited by 33 publications

(52 citation statements)

References 26 publications

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“…A previous study indicated the effects of plasma homocysteine level on the association between C677T and A1298C or G1793A (3). Further studies are required to determine the effects of fitness on the association between arterial stiffness and MTHFR haplotype.…”

Section: Discussionmentioning

confidence: 98%

Lack of carotid stiffening associated with MTHFR 677TT genotype in cardiorespiratory fit adults

Iemitsu

Murakami

Sanada

et al. 2010

Physiological Genomics

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The TT genotype of C677T polymorphism in 5,10-methylenetetrahydrofolate reductase (MTHFR) induces elevation of homocysteine level and leads to atherosclerosis and arterial stiffening. Furthermore, cardiorespiratory fitness level is also associated with arterial stiffness. In the present study, a cross-sectional investigation of 763 Japanese men and women (18 -70 yr old) was performed to clarify the effects of cardiorespiratory fitness on the relationship between arterial stiffness and MTHFR C677T gene polymorphism. Arterial stiffness was assessed by carotid ␤-stiffness with ultrasonography and tonometry. The study subjects were divided into high-cardiorespiratory fitness (HighFit) and low-cardiorespiratory fitness (Low-Fit) groups based on the median value of peak oxygen uptake in each sex and decade. The plasma homocysteine level was higher in the TT genotype of MTHFR C677T polymorphism compared with CC and CT genotype individuals. MTHFR C677T polymorphism showed no effect on carotid ␤-stiffness, but there was a significant interaction effect between fitness and MTHFR C677T polymorphism on carotid ␤-stiffness (P ϭ 0.0017). In the Low-Fit subjects, carotid ␤-stiffness was significantly higher in individuals with the TT genotype than the CC and CT genotypes. However, there were no such differences in High-Fit subjects. In addition, ␤-stiffness and plasma homocysteine levels were positively correlated in Low-Fit subjects with the TT genotype (r ϭ 0.71, P Ͻ 0.0001), but no such correlations were observed in High-Fit subjects. In CC and CT genotype individuals, there were also no such correlations in either fitness level. These results suggest that the higher cardiorespiratory fitness may attenuate central artery stiffening associated with MTHFR C677T polymorphism. peak oxygen uptake; arterial stiffness; homocysteine; 5,10-methylenetetrahydrofolate reductase ELEVATED PLASMA HOMOCYSTEINE level is considered a risk factor for cardiovascular events and is associated with arterial stiffness and atherosclerosis in subjects with some cardiovascular risk factors (7,15,30,36). High homocysteine levels may impair endothelial function, increase oxidative stress, and alter protein structure (5, 6, 37). Exposure of endothelial cells to elevated homocysteine levels results in decreased availability of nitric oxide (NO), which has vasodilatory and antiplatelet effects, and impaired vascular function, which are early events in atherogenesis (6,29,33,35). Homocysteine metabolism represents an interesting model of gene-environment interaction (34,38). Elevations in homocysteine may be caused by genetic and environmental factors and by gene-gene and/or geneenvironment interactions. The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) catalyzes the irreversible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate (4). A polymorphism of C677T (Ala¡Val) in the gene encoding MTHFR is associated with decreased activity of the enzyme due to thermolability (1). In individuals homozygous for the T (Val) allele, a r...

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Section: Discussionmentioning

confidence: 98%

Lack of carotid stiffening associated with MTHFR 677TT genotype in cardiorespiratory fit adults

Iemitsu

Murakami

Sanada

et al. 2010

Physiological Genomics

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“…The control group consisted of 1,079 individuals from a cross-sectional population studied in central Sweden, the same area in which our group of infertile women was recruited. The data concerning the control individuals have already been published (19)(20)(21)(22).…”

Section: Materials and Methods Subjectsmentioning

confidence: 99%

“…Previously described Pyrosequencing assays (19)(20)(21)(22) (Biotage AB, Uppsala, Sweden) were used to genotype the polymor-…”

Section: Genotypingmentioning

confidence: 99%

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Variations in folate pathway genes are associated with unexplained female infertility

Altmäe

Stavréus-Evers

Ruiz

et al. 2010

Fertility and Sterility

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“…Conversely, the carriers of the 677TT genotype accumulate formylated folates, which points to a disruption of the folate cycle [25,26]. The 677C>T substitution is the most common missense variation of MTHFR , with a global prevalence of 40% [25].…”

Section: Mthfr Genementioning

confidence: 99%

Folic Acid and Homocysteine in Chronic Kidney Disease and Cardiovascular Disease Progression: Which Comes First

Cianciolo

Pascalis²,

Lullo

et al. 2017

Cardiorenal Med

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Background: Hyperhomocysteinemia (Hhcy) occurs in about 85% of chronic kidney disease (CKD) patients because of impaired renal metabolism and reduced renal excretion. Folic acid (FA), the synthetic form of vitamin B₉, is critical in the conversion of homocysteine (Hcy) to methionine. If there is not enough intake of FA, there is not enough conversion, and Hcy levels are raised. Summary: Hhcy is regarded as an independent predictor of cardiovascular morbidity and mortality in end-stage renal disease. Hhcy exerts its pathogenic action on the main processes involved in the progression of vascular damage. Research has shown Hhcy suggests enhanced risks for inflammation and endothelial injury which lead to cardiovascular disease (CVD), stroke, and CKD. FA has also been shown to improve endothelial function without lowering Hcy, suggesting an alternative explanation for the effect of FA on endothelial function. Recently, the role of FA and Hhcy in CVD and in CKD progression was renewed in some randomized trials. Key Messages: In the general population and in CKD patients, it remains a topic of discussion whether any beneficial effects of FA therapy are to be referred to its direct effect or to a reduction of Hhcy. While waiting for the results of confirmatory trials, it is reasonable to consider FA with or without methylcobalamin supplementation as appropriate adjunctive therapy in patients with CKD.

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Association of total plasma homocysteine with methylenetetrahydrofolate reductase genotypes 677C>T, 1298A>C, and 1793G>A and the corresponding haplotypes in Swedish children and adolescents

Cited by 33 publications

References 26 publications

Lack of carotid stiffening associated with MTHFR 677TT genotype in cardiorespiratory fit adults

Lack of carotid stiffening associated with MTHFR 677TT genotype in cardiorespiratory fit adults

Variations in folate pathway genes are associated with unexplained female infertility

Folic Acid and Homocysteine in Chronic Kidney Disease and Cardiovascular Disease Progression: Which Comes First

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