• Clinical and Experimental Reproductive Medicine
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• 제26권3호
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• pp.441-445
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• 1999

Objective: To analyze the methylenetetrahydrofolate reductase (MTHFR) mutation in recurrent spontaneous abortion associated with hyperhomocysteinemia. Material and Method: The blood sample of habitual aborter with high fasting homocysteine level was tested by PCR - RFLP method. Results: The patient was found to be a homozygosity for MTHFR gene mutation that was confirmed by the finding which is consistent with the mutation at the nucleotide 677 C to T, corresponding to Ala to Val. Conclusions: Hyperhomocysteinemia due to MTHFR mutation is a cause of recurrent spontaneous abortion. Therefore, the MTHFR mutation should be examined in the workup of recurrent spontaneous abortion showing hyperhomocysteinemia.

• 대한예방의학회:학술대회논문집
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• 대한예방의학회 2004년도 제56차 추계 학술대회 연제집
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• pp.38.3-39
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• 2004

• Clinical and Experimental Reproductive Medicine
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• 제33권1호
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• pp.61-61
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• 2006

목 적: 본 연구는 methylenetetrahydrofolate reductase (MTHFR C677T와 A1298C) 유전자 돌연변이형이 자연유산아 발생의 원인 유전자로 작용하는지에 대해 알아보고자 시도하였다. 연구방법: 95명의 자연유산아 조직과 대조군으로 100명의 정상 소아의 혈액 그리고 449명의 정상 성인의 혈액을 채취하여 DNA를 분리하여 사용하였다. 유전자형은 분리된 DNA를 이용하여 중합효소 연쇄반응과 제한효소 절편다형 분석방법으로 결정하였다. 결 과: 자연유산아 그룹은 소아대조군에서 보다 MTHFR 677CC 형 (p=0.014)은 높게, 677CT형 (p=0.063)은 낮게 나타났다. 성인대조군과의 비교에서도 MTHFR 677CT 형의 빈도는 현저히 낮게 나타났다 (p=0.032). 그리고 MTHFR 677CC/1298AC 조합형 유전자의 경우 소아대조군 (p=0.034)과의 비교에서는 현저히 높은 빈도를 나타냈으나, 성인대조군 (p=0.063)과의 비교에서는 높은 경향성은 있었으나 통계학적으로 유의한 차이는 없었다. 결 론: MTHFR 677CC와 MTHFR 677CC/1298AC 유전자형은 자연유산아 발생의 위험인자일 가능성이 높으며, 지속적인 연구가 요구된다.

• 대한한방내과학회지
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• 제23권1호
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• pp.1-4
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• 2002

Objective : Hyperhomocysteinemia has been proven to be an independent risk factor for stroke. The genetic mutation of methylenetetrahydrofolate reductase(MTHFR) elevates serum homocysteine level, but it still remains controversial whether the MTHFR gene mutation could be a predictor of ischemic stroke. Therefore, we studied if this genetic defect could cause ischemic stroke independently. Methods : We gathered ischemic stroke subjects and age, sex-matched controls. Age, gender, past medical history, smoking habit, serum homocysteine level, and the MTHFR genotype were recorded. General characteristics of ischemic stroke subjects were compared to the controls. We classified the stroke according to the related vessels(small and large artery infarction) and single lesion and multiple infraction. Relevant risk of the MTHFR genotype was evaluated in each stroke subtype with multiple logistic regression analysis. Results : When the controls were compared to the whole ischemic stroke, there was no specific difference except some medical histories. However, further analysis based on stroke subtypes showed important results. The small artery infarction group, multiple infraction group had significant odds ratio of the MTHFR TT genotype adjusted for age, gender, medical history and smoking habit. Conclusions : The MTHFR TT genotype is an independent risk factor for certain types of ischemic stroke, small artery infarction and multiple infarction.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.299-302
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• 2013

Methylenetetrahydrofolate reductase (MTHFR) has been reported to be associated with DNA methylation, an epigenetic feature frequently found in gastric cancer. We conducted a case-control study to explore the association of MTHFR C677T polymorphisms with gastric cancer risk and its relation with the DNA methylation of COX-2, MGMT, and hMLH1 genes. Genotyping of P16, MGMT and HMLH1 was determined by methylation-specific PCR after sodium bisulfate modification of DNA, and genotyping of MTHFR C677T was conducted by TaqMan assays using the ABI Prism 7911HT Sequence Detection System. Folate intake was calculated with the aid of a questionnaire. Compared with the MTHFR 677CC genotype, the TT genotype was significantly associated with 2.08 fold risk of gastric cancer when adjusting for potential risk factors. Individuals who had an intake of folate above $310{\mu}g$/day showed protective effects against gastric cancer risk. The effect of MTHFR C677T polymorphisms on the risk of gastric cancer was modified by folate intake and methylation status of MGMT (P for interaction <0.05).

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2193-2197
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• 2012

Background: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate, and the role of MTHFR C677T polymorphism in cervical carcinogenesis is still controversial. Method: We performed a meta-analysis of all relevant case-control studies that examined any association between the C677T polymorphism and cervical cancer risk. We estimated summary odds ratios (ORs) with their confidence intervals (CIs) to assess links. Results: Finally, 10 studies with a total of 2113 cervical cancer cases and 2804 controls were included. Results from this meta-analysis showed that significantly elevated cervical cancer risk was associated with the MTHFR T allele in the Asian population under conditions of two genetic comparison models (for TT vs. CC, OR = 1.37, 95%CI 1.00-1.87, P = 0.050; for TT vs. TC+CC: OR = 1.34, 95%CI 1.01-1.77, P = 0.039). However, there was no obvious association between the MTHFR C677T polymorphism and cervical cancer risk in the other populations. Conclusion: The MTHFR C677T polymorphism is associated with cervical cancer risk in Asians, while any possible link in the Caucasian population needs further studies.

• Molecular & Cellular Toxicology
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• 제1권2호
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• pp.130-136
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• 2005

The purpose of this study was to evaluate whether the interactions between maternal folate deficiency and methylenetetrahydrofolate reductase (MTHFR) polymorphism increase the risk of elevated maternal serum homocysteine, short gestation and reduced infant birthweight. Healthy pregnant (n = 170; 24-28 gestational weeks; 20-40 years old) women were analyzed for the MTHFR genotype and serum levels of folate and homocysteine, and were then followed for gestational age and infant birthweight. The mean infant birthweight was highest in mothers carrying MTHFR CC and with a normal folate range, and they were followed by mothers carrying MTHFR CT or TT and a normal range of folate or a folate deficiency. Birthweight was the lowest in mothers whose carrying MTHFR CC with folate deficiency. Using two way ANOVA, we found that folate level and the MTHFR polymorphism interacted to affect birth-weight of infants (p=0.05). Among those mothers carrying MTHFR CC, those with folate deficiency showed a 543 g reduction in infant birthweight compared with those with normal folate levels. However, infant birthweight was no different for mothers, those who with folate deficiency compared to those with normal range of folate among mothers carrying the MTHFR CT or TT genotypes. This study suggests an interaction between maternal serum folate and the MTHFR polymorphisms of the mother on the risk of delivering reduced birthweight offspring. Folate supplementation of folate deficient pregnant women with the MTHFR wild type is suggested to reduce the risk of low birthweight.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9259-9264
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• 2014

Background: Previous studies concerning the association between the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism with lung cancer in Asian populations have provided inconclusive findings. Aim: A meta-analysis was performed to investigate a more reliable association between MTHFR C677T polymorphism and lung cancer in Asians. Materials and Methods: A comprehensive search was conducted to identify all case-control studies of MTHFR polymorphisms and lung cancer in Asia, using odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of any association. Results: Meta-analysis results suggested that the MTHFR C677T polymorphism contributed to an increased lung cancer risk in Asian populations (for T vs C: OR=1.11, 95%CI=1.0-1.23; for CT vs CC: OR= 1.1, 95%CI= 0.95-1.2 ; for TT+CT vs CC: OR=1.13, 95%CI=1.0-1.30; for TT vs CC: OR=1.25, 95%CI=1.01-1.30; for TT vs CT+CC: OR=1.16, 95%CI=1.0-1.36). Conclusions: MTHFR C677T polymorphism is significantly associated with lung cancer in Asians.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.3163-3168
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• 2013

Methylenetetrahydrofolate reductase (MTHFR) plays a central role in folate metabolism. This study with 381 esophageal cancer patients and 432 healthy controls was conducted to examine the association of MTHFR C677T and A1298C polymorphisms with susceptibility to esophageal cancer (EC) in a Chinese population. Compared with the CC genotype of MTHFR C677T, subjects carrying homozygote TT and variant genotypes (CT+TT) demonstrated reduced risk of EC with adjusted ORs (95% CI) of 0.44 (0.28-0.71) and 0.57 (0.37-0.88), respectively. However, no association was found between the MTHFR A1298C polymorphism and the risk of EC. Comparing to haplotype CA, haplotypes TA and TC could reduce the susceptibility to EC with adjusted ORs (95% CI) of 0.61(0.47-0.79) and 0.06 (0.01-0.43), respectively. In conclusion, the present study suggested that the MTHFR C677T polymorphism can markedly influence the risk of EC in Chinese.

• Journal of Nutrition and Health
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• 제35권10호
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• pp.1045-1052
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• 2002

Hyperhomocysteinemia, resulted from an interaction between the mutation of MTHFR gene and B vitamin deficiency, is suggested as a possible cause for complications and adverse outcomes of pregnancy. The purpose of the present study was to investigate the relationship between the intakes of B vitamins and serum homocysteine concentrations with the C677T mutation in the MTHFR genotypes in 135 normal pregnant women of 24-28 weeks of gestation. Dietary intake of B vitamins did not differ among the three genotypes, but the negative correlation between dietary folate intake and the serum homocysteine level was the strongest in the T/T type (r ＝ -0.249) than in other genotypes (C/T: r＝ -0.040, C/C:r＝ 0.126, p＜0.05). Among the subject with the T/T type, the pregnant women who consumed folate less than 50% of the RDA had higher serum homocysteine levels than those who consumed folate greater than 125% of the RDA (10.4$\pm$5.9 vs 7.0$\pm$1.5 $\mu$mol/L, p＜0.05). Serum homocysteine levels were higher in the women with micronutrient supplements than those with no supplements in the T/T type, but such relation was not present in the C/C or the C/T type. In conclusion, serum homocysteine concentrations were influenced by the interrelationship between the MTHFR polymorphisms and dietary folate intake or micronutrient supplementation.