Methylenetetrahydrofolate reductase polymorphism and pre-eclampsia.

Sohda, Satoshi; Arinami, Tadao; Hamada, Hiromi; Yamada, Naoki; Hamaguchi, Hideo; Kubo, Takuya

doi:10.1136/jmg.34.6.525

Cited by 204 publications

(104 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The biological rationale for implicating MTHFR C677T polymorphism in hypertension is based on the fact that MTHFR catalyses the formation of 5-methylenetetrahydrofolate, a co-substrate for the conversion of homocysteine to methionine, 33 with the 677TT genotype, via the creation of a thermolabile enzyme isoform, associating with elevated homocysteine, which may predispose to atherosclerosis by injuring the vascular endothelium, further resulting in hypertension, 34 which is consistent with the association results in this study. Therefore, it is reasonable to expect that multiple genetic and/or physiological safeguards have developed to maintain homocysteine within a range of physiologically acceptable levels, in a variety of environmental conditions.…”

Section: Discussionsupporting

confidence: 85%

Strong association of methylenetetrahydrofolate reductase gene C677T polymorphism with hypertension and hypertension-in-pregnancy in Chinese: a meta-analysis

2011

J Hum Hypertens

View full text Add to dashboard Cite

Attempts to associate methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with hypertension have been extensively evaluated, but mostly in Caucasians. We therefore meta-analysed this polymorphism in association with hypertension and hypertensionin-pregnancy (HIP) among Chinese subjects. A randomeffects model was applied irrespective of between-study heterogeneity, which was evaluated by subgroup and meta-regression analyses. Study quality was assessed in duplicate. Publication bias was weighed using Egger's test and funnel plot. Data on 20 qualified studies totalling 4461 Chinese subjects were meta-analysed. In overall allelic/genotypic models, carriers of 677T or 677TT were consistently at significantly increased risk of developing hypertension and HIP. No between-study heterogeneity was identified for all genetic models, with the exception for contrast of allele 677T versus 677C in hypertension association studies (P ¼ 0.03), and the dominant contrast in HIP association studies (P ¼ 0.025). Both the subgroup and meta-regression analyses indicated that study design was a potential source of between-study heterogeneity. Funnel plot and Egger's test suggested no evidence of publication bias. Taken together, our results supported the notion that carriers of 677T or 677TT were at significantly increased risk of developing hypertension and HIP, but indicated caution in interpreting this result, because the study design made marginal significant contribution to the heterogeneity.

show abstract

Section: Discussionsupporting

confidence: 85%

Strong association of methylenetetrahydrofolate reductase gene C677T polymorphism with hypertension and hypertension-in-pregnancy in Chinese: a meta-analysis

2011

J Hum Hypertens

View full text Add to dashboard Cite

show abstract

“…In 1997, two separate case-control studies independently reported a significant association between the TT genotype and preeclampsia (87,88) . Since then, numerous studies have investigated this association; however, conflicting results have emerged (Table 2).…”

Section: Role Of the Mthfr Genotype In Determining The Risk Of Hypertmentioning

confidence: 99%

“…Most recently, the meta-analysis by Xia et al (95) reported that the TT genotype compared with the CC and CT genotypes carried a significantly greater risk of preeclampsia (by 76%) among Asian women only, whereas in Caucasian women this increased risk was not evident. It is worth noting however that a much greater number of large-scale studies in this area have been conducted within Asian populations with far fewer studies conducted in Caucasian populations; a factor that limits Sohda et al (87) 425 Japan 2·5 (1·3, 4·8) Grandone et al (88) 225 Italy 1·8 (1·0, 3·5) Kupferminc (96) 144 Israel 2·9 (1·0, 8·5) Powers et al (97) 237 Caucasian women 1·28 (0·58, 2·79) Kobashi et al (98) 316 Japan 0·68 (0·30, 1·55) Laivuori et al (99) 216 Finland 0·50 (0·14, 1·77) Rigo et al (100) 221 Caucasian women 1·13 (0·38, 3·37) Morrison et al (101) 404 Scotland 1·00 (0·55, 1·82) Prasmusinto et al (102) 112 Germany and Croatia 0·28 (0·03, 2·47) Pegoraro et al (103) 609 South African (Black) 0·62 (0·06, 6·90) Perez-Mutul et al (91) 325 Mexico 0·94 (0·59, 1·49) Williams et al (104) 304 Peru 1·6 (0·7, 3·8) Yilmaz et al (105) 111 Turkey 0·84 (0·26, 2·67) Also-Rallo et al (79) 165 Spain 0·73 (0·31, 1·76) Hernandez-Diaz et al (86) 154 USA/Canada 3·0 (1·2, 7·7) Stiefel et al (106) 584 Spain 0·92 (0·50, 1·71) the extent to which different populations can be compared. An additional limitation is that genotype-driven recruitment is generally not undertaken in these studies, a feature that is reflected by the relatively small numbers of pregnant women with the TT genotype being investigated and these raised the concern that many such studies may be statistically underpowered.…”

Section: Role Of the Mthfr Genotype In Determining The Risk Of Hypertmentioning

confidence: 99%

MTHFR677TT genotype and disease risk: is there a modulating role for B-vitamins?

et al. 2013

View full text Add to dashboard Cite

Methylenetetrahydrofolate reductase (MTHFR) is a critical folate-metabolising enzyme which requires riboflavin as its co-factor. A common polymorphism (677C→T) in the MTHFR gene results in reduced MTHFR activity in vivo which in turn leads to impaired folate metabolism and elevated homocysteine concentrations. Homozygosity for this polymorphism (TT genotype) is associated with an increased risk of a number of conditions including heart disease and stroke, but there is considerable variability in the extent of excess risk in various reports. The present review will explore the evidence which supports a role for this polymorphism as a risk factor for a number of adverse health outcomes, and the potential modulating roles for B-vitamins in alleviating disease risk. The evidence is convincing in the case which links this polymorphism with hypertension and hypertensive disorders of pregnancy, particularly preeclampsia. Furthermore, elevated blood pressure was found to be highly responsive to riboflavin intervention specifically in individuals with the MTHFR 677TT genotype. Future intervention studies targeted at these genetically predisposed individuals are required to further investigate this novel gene–nutrient interaction. This polymorphism has also been associated with an increased risk of neural tube defects (NTD) and other adverse pregnancy outcomes; however, the evidence in this area has been inconsistent. Preliminary evidence has suggested that there may be a much greater need for women with the MTHFR 677TT genotype to adhere to the specific recommendation of commencing folic acid prior to conception for the prevention of NTD, but this requires further investigation.

show abstract

“…A common polymorphism in methylene-tetrahydro-folate-reductase (MTFHR 677C>T, a C to T substitution at nucleotide 677, which converts alanine to a valine residue) has been identified as responsible for reduced MTHFR activity and increased plasma homocysteine [10,11].…”

Section: Discussionmentioning

confidence: 99%

“…The lack of association may be in part due to variation of incidence of retinopathy and preeclampsia in different population rather than diagnostic criteria; in addition, other background genetic factors may still be involved [8]. Thus, ameliorating the proposed effects of hyperhomocysteinemia with folic acid, vitamin B6, and anticoagulants has proved inconclu sive in prophylaxis on preeclampsia [9,11,30].…”

Section: Mtfhr-mentioning

confidence: 99%

Retinopathy in pregnancy in women with type 1 diabetes - a study of associations with arterial wall elasticity and mutation in coagulation genes

Lauszus¹,

Grøn²,

Tjessem³

et al. 2017

Integr Obesity Diabetes

View full text Add to dashboard Cite

Aim: The arterial wall elasticity and genetic setting is a potential risk factor for dysfunction of vas¬cular endothelial cells and the clinical expression of retinopathy. The prevalence was evaluated of polymorphism in the genes of methylene-tetrahydro-folate-reductase (MTFHR), Factor V, glycoprotein IIb/IIIa (Gp2b3a), and prothrombin in a cohort of pregnant women with type 1 diabetes. The role of hyperhomo¬cysteinemia in microangiopathy in diabetes mellitus has been debated and is mainly seen with reduced activity of the MTHFR gene. The arterial resistance index (AASI) has been used to detect arterial dysfunction and correlate with cardiovascular morbidity and mortality in patients with hypertension.Design: Two-hundred-and-thirty-three women with type 1 diabetes mellitus were analyzed for MTHFR gene polymorphism and Factor V Leiden. In 176 of these women AASI was further evaluated. In a sub-cohort of 40 women with preeclampsia, mutations in glycoprotein IIb/IIIa (Gp2b3a) and prothrombin was measured. The pregnancy and ophthalmological examination data charts were reviewed retrospectively.Results: Retinopathy was associated with higher AASI during pregnancy (p<0.01, in all three trimesters) and preeclampsia (p<0.05). The stiffness increased with higher grades of retinopathy. AASI in women with simplex and proliferative retinopathy followed different patterns during the three trimesters, even when adjusted for age, BMI, and glycemic regulation (p<0.01). None of the studied coagulation genes (MTHFR, Factor V, Gp2b3a, and prothrombin) were found associated with retinopathy or preeclampsia. Conclusion:Retinopathy showed a strong association with AASI during pregnancy and not outside pregnancy in women with type 1 diabetes. This suggests a pregnancy-related functional change in the vascular bed.A common polymorphism in methylene-tetrahydro-folate-reductase (MTFHR 677C>T, a C to T substitution at nucleotide 677, which converts alanine to a valine residue) has been identified as responsible for reduced MTHFR activity and increased plasma homocysteine [10,11].Factor V Leiden is a mutated form of human factor V that causes an increase in blood clotting. With this mutation, the anticoagulant protein secreted is inhibited, leading to an increased tendency to form dangerous, abnormal blood clots. Factor V Leiden is the most common hereditary hypercoagulability disorder amongst ethnic Europeans and linked with increased risk of preeclampsia, abortions, intrauterine growth restriction, placental abruption, and thrombosis [12][13][14].Glycoprotein IIb/IIIa (Gp2b3a, also known as integrin αIIbβ3) is a complex found on platelets. It is a receptor for fibrinogen and von Lauszus FF (2017) Retinopathy in pregnancy in women with type 1 diabetes -a study of associations with arterial wall elasticity and mutation in coagulation genes

show abstract

Methylenetetrahydrofolate reductase polymorphism and pre-eclampsia.

Cited by 204 publications

References 4 publications

Strong association of methylenetetrahydrofolate reductase gene C677T polymorphism with hypertension and hypertension-in-pregnancy in Chinese: a meta-analysis

Strong association of methylenetetrahydrofolate reductase gene C677T polymorphism with hypertension and hypertension-in-pregnancy in Chinese: a meta-analysis

MTHFR677TT genotype and disease risk: is there a modulating role for B-vitamins?

Retinopathy in pregnancy in women with type 1 diabetes - a study of associations with arterial wall elasticity and mutation in coagulation genes

Contact Info

Product

Resources

About