Absence of association between a common mutation in the methylenetetrahydrofolate reductase gene and preeclampsia in Japanese women

Kobashi, Gén; Yamada, Hideto; Asano, Tomohiko; Nagano, S; Hata, Akira; Kishi, Reiko; Fujimoto, Seiichiro; Kondo, Kiyotaro

doi:10.1002/1096-8628(20000717)93:2<122::aid-ajmg8>3.0.co;2-z

Cited by 47 publications

(21 citation statements)

References 24 publications

(30 reference statements)

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“…The main characteristics of the included studies are presented in Table S1. Among all studies, 42 studies were performed among East Asians [27], [28], [33], [37], [42], [43], [48], [50], [54], [56], [57], [60], [65], [73], [75], [78], [79], [81], [86]–[90], [94]–[97], [102], [103], [105]–[107], [115]–[118], [122], [124], [131], [132], [134], [136], 54 among Caucasians [29], [31], [32], [34], [35], [38]–[41], [44]–[47], [49], [51]–[53], [55], [59], [63], [64], [66], [67], [69]–[72], [74], [76], [77], [80], [82], [84], [92], [93], [98]–[101], …”

Section: Resultsmentioning

confidence: 99%

Associations of MTHFR Gene Polymorphisms with Hypertension and Hypertension in Pregnancy: A Meta-Analysis from 114 Studies with 15411 Cases and 21970 Controls

et al. 2014

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BackgroundSeveral epidemiological studies have investigated the associations of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms with hypertension (H) or hypertension in pregnancy (HIP). However, the results were controversial. We therefore performed a comprehensive meta-analysis to provide empirical evidences on the associations.MethodologiesThe English and Chinese databases were systematically searched to identify relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations. Meta-regression, subgroup analysis, sensitivity analysis, cumulative meta-analysis and assessment of publication bias were performed in our study.Principal FindingsA total of 114 studies with 15411 cases and 21970 controls were included, 111 studies with 15094 cases and 21633 controls for the C677T polymorphism and 21 with 2533 cases and 2976 controls for the A1298C polymorphism. Overall, the C677T polymorphism was significantly associated with H and HIP (H & HIP: OR = 1.26, 95% CI = 1.17–1.34; H: OR = 1.36, 95% CI = 1.20–1.53; HIP: OR = 1.21, 95% CI = 1.08–1.32). Stratified analysis by ethnicity revealed a significant association among East Asians and Caucasians, but not among Latinos, Black Africans, and Indians and Sri Lankans. In the stratified analyses according to source of controls, genotyping method, sample size and study quality, significant associations were observed in all the subgroups, with the exception of population based subgroup in H studies and large sample size and “others” genotyping method subgroups in HIP studies. For the A1298C polymorphism, no significant association was observed either in overall or subgroup analysis under all genetic models.ConclusionsThis meta-analysis suggests that the MTHFR C677T rather than A1298C polymorphism may be associated with H & HIP, especially among East Asians and Caucasians.

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Section: Resultsmentioning

confidence: 99%

Associations of MTHFR Gene Polymorphisms with Hypertension and Hypertension in Pregnancy: A Meta-Analysis from 114 Studies with 15411 Cases and 21970 Controls

et al. 2014

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“…The frequency of T-carriers genotypes was found significantly higher among the women with PE than the control groups indicated that MTHFR C677T polymorphism would be expected to play a major role to bring about PE. Some studies reported significantly increased prevalence of MTHFR C677T among cases [22][23][24]49]. In contrast, other 1 9 9 7 J a p a n A s i a n Three meta-analysis summarizing studies on association between the MTHFR C677T polymorphism and the risk of PE until August 2012 have been performed [51][52][53], however, their meta-analysis did not perform analyses on association between the MTHFR A1298C and the risk of PE.…”

Section: Discussionmentioning

confidence: 99%

Folate metabolism gene polymorphisms MTHFR C677T and A1298C and risk for preeclampsia: a meta-analysis

Yang

Tang

et al. 2015

J Assist Reprod Genet

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Objectives MTHFR C677T and A1298C have been associated with the risk of preeclampsia (PE), but with conflicting results. We performed this meta-analysis to derive a more precise estimation of the association between MTHFR polymorphisms and PE. Study design An electronic search of PubMed and Chinese Biomedicine database was conducted to select studies for meta-analysis. 54 case controlled studies containing MTHFR C677T and A1298C gene polymorphisms were chosen, and odds ratio (OR) with confidence interval (CI) was used to assess the strength of this association. Result These studies evaluated 7398 cases and 11230 controls for MTHFR C677T. The overall results suggested that MTHFR C677T was associated with the risk of PE. (T vs. C: OR = 1.157, 95 % CI: 1.057-1.266, p=0.002; TT+CT vs. CC: OR=1.165, 95 % CI 1.049-1.293, P = 0.004; TT vs. CT + CC: OR = 1.371, 95 % CI: 1.153-1.63, p < 0.001). We also evaluated 1103 cases and 988 controls for MTHFR A1298C but could not demonstrate an increased risk of PE for this polymorphism (p=0.667). A symmetric funnel plot, the Egger's test (p = 0.819) suggested a lack of publication bias. ConclusionThis meta-analysis supports the idea that MTHFR C677T genotype is associated with increased risk for PE, especially in the case of Asians and Caucasians.

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“…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

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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.

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Absence of association between a common mutation in the methylenetetrahydrofolate reductase gene and preeclampsia in Japanese women

Cited by 47 publications

References 24 publications

Associations of MTHFR Gene Polymorphisms with Hypertension and Hypertension in Pregnancy: A Meta-Analysis from 114 Studies with 15411 Cases and 21970 Controls

Associations of MTHFR Gene Polymorphisms with Hypertension and Hypertension in Pregnancy: A Meta-Analysis from 114 Studies with 15411 Cases and 21970 Controls

Folate metabolism gene polymorphisms MTHFR C677T and A1298C and risk for preeclampsia: a meta-analysis

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

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