No Association of C677T Methylenetetrahydrofolate Reductase and an Endothelial Nitric Oxide Synthase Polymorphism with Recurrent Pregnancy Loss

Makino, Aiko; Nakanishi, Tamao; Sugiura‐Ogasawara, Mayumi; Ozaki, Yasuhiko; Suzumori, Nobuhiro; Suzumori, Kaoru

doi:10.1111/j.1600-0897.2004.00187.x

Cited by 56 publications

(45 citation statements)

References 35 publications

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“…Smallest sample size was 24 [41] and largest sample size was 329 [50]. Seven studies did not show any association between C677T polymorphism and RPL risk [21,28,29,37,43,47,52], remaining twenty-two studies showed significant association. In twenty-nine studies, total cases were 3725 with CC (1971), CT (1325) and TT (429), and controls were 4105 with CC (2545), CT (1218), and TT (342).…”

Section: Characteristics Of Included Studiesmentioning

confidence: 92%

“…All these twenty-five studies were performed in different countries like-Behrain [47], China [38-40, 42, 44, 46, 54], Egypt [52], India [11,21,29,30,41,48,49,57], Iran [28,51,53,55,56], Israel [15,37], Japan [43,45], Palestine [50], SriLanka [16], Turkey [27]. Smallest sample size was 24 [41] and largest sample size was 329 [50].…”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

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Methylenetetrahydrofolate Reductase C677T Polymorphism and Recurrent Pregnancy Loss Risk in Asian Population: A Meta-analysis

Rai

2016

Ind J Clin Biochem

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The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene was implicated to be associated with thrombophilia due to its role in catalyzing the formation of 5-methylenetetrahydrofolate, a co-substrate for the conversion of homocysteine to methionine. Several case-control studies were investigated MTHFR C677T polymorphism as risk for recurrent pregnancy loss (RPL). These studies rendered contradictory results, some indicating that the polymorphism is associated with the risk of RPL whereas others concluded there is no association. To shed light on these inconclusive findings, a meta-analysis of all available studies published from Asian population relating the C677T polymorphism to the risk of RPL was conducted. The following electronic databases were searched without language restrictions: PubMed, Google Scholars, Elsevier and Springer Link up to December, 2015. Meta-analysis was performed using MetaAnalyst and Mix version 1.7. Meta-analysis results suggested that MTHFR C677T polymorphism contributed to the increased RPL risk in Asian population using all five genetic models (for T vs. C: OR 1.35, 95 % CI 1.09-1.68, p = 0.009; for TT ? CT vs. CC: OR 1.44, 95 % CI 1.14-1.82, p = 0.006; for CT vs. CC: OR 1.39, 95 % CI 1.07-1.8, p = 0.01; for TT vs. CC: OR 1.79, 95 % CI 1.23.2.6, p = 0.007; for TT vs. CT ? CC: OR 1.61, 95 % CI 1.02-2.56, p = 0.04). In conclusion, this meta-analysis demonstrates a strong association between the MTHFR C677T variant and RPL in Asian population and raising the importance of the use of folate in its treatment and prevention.

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Section: Characteristics Of Included Studiesmentioning

confidence: 92%

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

Methylenetetrahydrofolate Reductase C677T Polymorphism and Recurrent Pregnancy Loss Risk in Asian Population: A Meta-analysis

Rai

2016

Ind J Clin Biochem

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“…Hyperhomocysteinemia caused by MTHFR mutations or folate deficiency was associated with placental abruption or infarction (Van der Molen et al 2000), pre-eclampsia (Lachmeijer et al 2001, Murakami et al 2001, pregnancy-associated hypertension (Kosmas et al 2004) and RPL (Nelen et al 2000a, Unfried et al 2002. Others failed to demonstrate any association between MTHFR SNPs, hyperhomocysteinemia and RPL (Foka et al 2000, Makino et al 2004, as similar (Holmes et al 1999) or even lower (Makino et al 2004) prevalence rates of MTHFR C677T SNP were seen in patients compared with women with uneventful pregnancies. This prompted us to assess the relationship between RPL, MTHFR C677T and A1298C SNPs and tHcy in 200 Tunisian women with three or more consecutive idiopathic miscarriages, compared with 200 parous women of similar ethnic background with uncomplicated pregnancies and deliveries.…”

Section: Introductionmentioning

confidence: 99%

Methylenetetrahydrofolate reductase C677T and A1298C polymorphism and changes in homocysteine concentrations in women with idiopathic recurrent pregnancy losses

Mtiraoui¹,

Zammiti²,

Ghazouani³

et al. 2006

Reproduction

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Because they have been described as strong risk factors for idiopathic recurrent pregnancy losses (RPLs), we assessed the association between the methylenetetrahydrofolate reductase (MTHFR) single-nucleotide polymorphisms (SNPs) C677T and A1298C and hyperhomocysteinemia in Tunisian women with idiopathic RPL. Study subjects comprised 200 patients with more than three consecutive RPLs, and 200 age-matched parous control women. C677T and A1298C SNPs were analyzed by PCR-RFLP analysis, and fasting serum homocysteine was measured with ELISA. The frequency of MTHFR 677T/T (30.0 vs 7.0%) and 1298C/C (13.5 vs 4.0%) genotypes was significantly higher in patients. While it was similar among patients and controls (P 5 0.095), higher homocysteine was seen with the T/T (but not 1298A/C and 1298C/C) genotype among patients and controls compared with non-T/T carriers (P < 0.05), and in patients vs controls. Higher prevalence of MTHFR 677T/T was seen in late (P < 0.05) and early-late (P < 0.001) RPL, while higher prevalence of 1298C/C genotype was seen only in earlylate RPL (P < 0.001), and the prevalence of double heterozygotes was statistically not significant between patients and controls (P 5 0.10; odds ratio 5 2.73). Logistic regression analysis showed that, after adjusting for all variables, homozygosity for MTHFR C677T was associated with late (P < 0.001), and combined early-late (P < 0.001), while homozygosity for A1298C was associated only with combined early-late (P 5 0.026), as was secondary-level education, which was associated with early (P 5 0.005), late (P 5 0.026) and combined early-late (P 5 0.004) abortions. Homozygosity for MTHFR C677T (late and early-late) and A1298C (early-late) are risk factor for RPLs, irrespectively of total homocysteine levels.

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“…The results of investigations about whether MTHFR gene mutation increases the risk for recurrent abortion is still controversial. 17,18 Whereas the ratio of MTHFR C677T gene mutation among patients with a history of recurrent abortion has been found as 30%, while it was 7% for control group. 19 This data is in concordance with the findings of our study that indicate high levels of MTH-FR gene mutation.…”

Section: Discussionmentioning

confidence: 99%

Thrombophilic risk factors in women with recurrent abortion

Yokuş

Balçık²,

Albayrak³

et al. 2010

J Clin Exp Invest

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No Association of C677T Methylenetetrahydrofolate Reductase and an Endothelial Nitric Oxide Synthase Polymorphism with Recurrent Pregnancy Loss

Abstract: We conclude that the NO concentration but not the polymorphism of MTHFR and eNOS gene and hyperhomocysteinemia are associated with recurrent pregnancy loss in Japanese.

Cited by 56 publications

References 35 publications

Methylenetetrahydrofolate Reductase C677T Polymorphism and Recurrent Pregnancy Loss Risk in Asian Population: A Meta-analysis

Methylenetetrahydrofolate Reductase C677T Polymorphism and Recurrent Pregnancy Loss Risk in Asian Population: A Meta-analysis

Methylenetetrahydrofolate reductase C677T and A1298C polymorphism and changes in homocysteine concentrations in women with idiopathic recurrent pregnancy losses

Thrombophilic risk factors in women with recurrent abortion

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