Jeon, Nick-Beom;Ji, Seung Il;Shin, Seung Joo;Cha, Sun Hee;Choi, Dong Hee;Yim, Dong Jin;Park, Sang Hee;Lee, Suman;Lee, Sang Hwa;Ko, Jung Jae;Kim, Nam Keun
Clinical and Experimental Reproductive Medicine
/
v.33
no.1
/
pp.61-61
/
2006
Objectives : This study was performed to understand the influence of the methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) genotypes on the spontaneously aborted embryos. Methods : DNA was extracted from tissue samples of 95 spontaneously aborted embryos and 100 samples of normal children randomly and 449 samples of normal adults were selected as the controls. MTHFR genotypes were determined by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Results : The aborted embryo group had higher frequency of MTHFR 677CC type (p=0.014) and lower 677CT type (p=0.063) than the controlled child group. The frequency of MTHFR 677CT type was drastically lower than that of controlled adult group (p=0.032). In the MTHFR C677T/A1298C combination, 677CC/1298AC genotype of the aborted embryo was significantly higher (p=0.034) than that of controlled child group, but it was not statistically significant in controlled adult group (p=0.063). Conclusion : MTHFR 677CC and MTHFR 677CC/1298AC genotypes may represent genetic markers for the risk of spontaneously aborted embryos at least in Koreans.
Park, Hye-Sook;Kim, Young-Ju;Ha, Eun-Hee;Lee, Bo-Eun;Park, Bo-Hyun;Lee, Hwa-Young;Park, Eun-Ae;Chang, Nam-Soo;Hong, Yun-Chul
Molecular & Cellular Toxicology
/
v.1
no.2
/
pp.130-136
/
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.
Aim: We aimed to investigate the associations of dietary intake of folate, vitamin $B_6$ and $B_{12}$ and MTHFR genotype with breast cancer in a Chinese population. Methods: A matched case-control study was conducted, and 435 patients with newly diagnosed and histologically confirmed breast cancer and 435 controls were collected. The folate intake, vitamin $B_6$ and vitamin $B_{12}$ were calculated, and MTHFR C665T, C677T and A1298C were analyzed by PCR-RFLP. Results: We found vitamin $B_{12}$ was likely to reduce the risk of breast cancer, and MTHFR 665TT was associated with increased risk of breast cancer. Folate intake, vitamin $B_{12}$ intake and variants of MTHFR C677T and MTHFR A1298C demonstrated no association with risk of breast cancer. However, we found patients with low intake of vitamin $B_6$ and MTHFR 665TT genotype had a higher risk of breast cancer (OR=1.87, 95% CI=1.29-2.77), the association being less pronounced among subjects with a moderate intake of vitamin $B_6$ and MTHFR 665TT genotype (OR=1.58, 95% CI=1.03-2.49, P=0.03). Conclusion: Our study indicated that the MTHFR C665T polymorphism and vitamin $B_6$ are associated with risk of breast cancer, which indicated roles for nutrients in developing breast cancer.
Purpose: Hypermethylation of human mut L homologue 1 (hMLH1) promoter region is known to cause sporadic microsatellite instability (MSI) colorectal cancers. 5,10-methylenetetrahydrofolate reductase (MTHFR) is the key enzyme in folate metabolism, acting as a methyl donor for DNA methylation. In this study, we investigate whether the polymorphism of MTHFR 677C>T plays a role in the alteration of the promoter-specific hypermethylation, predisposing to MSI colorectal cancers. Methods: Total of 487 sporadic colorectal cancer patients in CHA Bundang Medical Center were collected. MSI was identified when two or more are positive among five microsatellite markers (BAT25, BAT26, D17S250, D5S346, D2S123). The others were classified as microsatellite stable (MSS). Polymorphism of MTHFR 677C>T was genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: MSI was observed in 65 of 487 patients (12.73%). MSI colorectal cancers showed similar clinicopathological features with previously reported; younger age onset, right-sided preponderance, mucinous and poorly differentiated histology, lower stage, fewer lymph node metastases than MSS tumors (each P<0.05). The frequency of MTHFR 677TT genotype was 17.7% in the MSI group higher than 14.6% in the MSS group (P=0.17). Although not statistically significant, compared to the MTHFR 677CC referent, MTHFR 677 CT+TT genotype was more likely to have MSI than MSS (odds ratio, 1.81; 95% confidence interval, 0.94 to 3.68; P=0.06). Conclusion: This study demonstrated higher frequency of MTHFR 677TT genotype in MSI colorectal cancers. Furthermore, individuals with MTHFR 677CT+TT variant type might potentially develop MSI rather than MSS colorectal cancers.
Kim, Nam-Keun;Nam, Yoon-Sung;Lee, Su-Man;Kim, Sun-Hee;Shin, Seung-Joo;Chang, Sung-Woon;Kim, Se-Hyun;Cha, Kwang-Yul;Oh, Do-Yeun
Clinical and Experimental Reproductive Medicine
/
v.29
no.3
/
pp.215-222
/
2002
Objective : Previous studies have suggested that hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR C677T) mutations are associated with increased risk of recurrent spontaneous abortion (RSA). Recently, a second site polymorphism in MTHFR, 1298A-->C, which changes a glutamic acid into an alanine residue, was shown to be associated with a decreased enzyme activity. We tested whether the variant alleles of MTHFR C677T and A1298C are risk factor (biomarker) for RSA. Materials and Methods: We analyzed DNA from a case-control study in the Korean DNA was extracted from blood samples of 118 patients with RSA and 123 healthy fertile patients as the controls. MTHFR variant alleles were determined by a PCR-restriction fragment length polymorphism assay. Results: We found no evidence for an association between 677TT genotype and risk of RSA (OR=1.95, 95% CI=$0.84{\sim}4.50$, p=0.12). However, the MTHFR 1298AC (OR=0.36, 95% CI=$0.20{\sim}0.63$, p=0.0004) and 1298AC+CC (OR=0.35, 95% CI=$0.20{\sim}0.61$, p=0.0002) genotypes were lower among 118 RSA cases compared with 123 controls, conferring a 2.8-fold decrease in risk of RSA, respectively. Moreover, the combined genotypes of MTHFR 677CC/1298AC (OR=0.30, 95% CI=$0.10{\sim}0.88$, p=0.029) and 677CT/1298AC (OR=0.77, 95% CI=$0.60{\sim}0.99$, p=0.043) also showed significantly lower risk than those with MTHFR 677CC/1298AA type. Conclusion: MTHFR 1298AC, MTHFR 677CC/1298AC and 677CT/1298AC genotypes may represent genetic markers for the protection of RSA at least in Korean women.
Lee, Young Sik;Jeon, Chang Moo;Na, Chul;Chae, Seok Lae
Korean Journal of Biological Psychiatry
/
v.12
no.2
/
pp.114-122
/
2005
Objectives:Recently in schizophrenia high incidence of MTHFR(methylenetetrahydrofolate reductase), which is a main relating enzyme that reduce homocysteine level, genetic variations were reported. So we examined serum homocysteine level and MTHFR gene polymorphism in Korean schizophrenics. Method:We compared serum homocysteine level and MTHFR polymorphism between 235 schizophrenics (100male, 135female) and 235 normal controls(100male, 135female). C677T and A1298C polymorphism of MTHFR gene were analyzed. Results:1) C677T genetic mutation(CT and TT) were more frequent in schizophrenia group than normal control group(p<0.01). But the difference of A1298C mutation frequency was not found between two groups. 2) In schizophrenia patients, TT genotype of C677T mutation showed significantly higher homocysteine level (29.99uM/L) than other group(CT:13.34uM/L, CC:9.34uM/L p<0.01). 3) MTHFR 677 TT homogeneous mutation genotype showed two times more risk(odds ratio=2.15) than 677CC normal genotype in schizophrenia. Conclusion:Some schizophrenia patients with high homocysteine serum level may have C677T TT genotype. In that case, folate ingestion could be a good management for clinical improvement.
Background: Genetic and environmental factors play important roles in pathogenesis of digestive tract cancers like those in the esophagus, stomach and colorectum. Folate deficiency and methylenetetrahydrofolate reductase (MTHFR) as an important enzyme of folate and methionine metabolism are considered crucial for DNA synthesis and methylation. MTHFR variants may cause genomic hypomethylation, which may lead to the development of cancer, and MTHFR gene polymorphisms (especially C677T and A1298C) are known to influence predispositions for cancer development. Several case control association studies of MTHFR C677T polymorphisms and colorectal cancer (CRC) have been reported in different populations with contrasting results, possibly reflecting inadequate statistical power. Aim: The present meta-analysis was conducted to investigate the association between the C677T polymorphism and the risk of colorectal cancer. Materials and Methods: A literature search of the PubMed, Google Scholar, Springer link and Elsevier databases was carried out for potential relevant articles. Pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated to assess the association of MTHFR C677T with the susceptibility to CRC. Cochran's Q statistic and the inconsistency index (I2) were used to check study heterogeneity. Egger's test and funnel plots were applied to assess publication bias. All statistical analyses were conducted by with MetaAnalyst and MIX version 1.7. Results: Thirty four case-control studies involving a total of 9,143 cases and 11,357 controls were retrieved according to the inclusion criteria. Overall, no significant association was found between the MTHFR C677T polymorphism and colorectal cancer in Asian populations (for T vs. C: OR=1.03; 95% CI= 0.92-1.5; p= 0.64; for TT vs CC: OR=0.88; 95%CI= 0.74-1.04; p= 0.04; for CT vs. CC: OR = 1.02; 95%CI= 0.93-1.12; p=0.59; for TT+ CT vs. CC: OR=1.07; 95%CI= 0.94-1.22; p=0.87). Conclusions: Evidence from the current meta-analysis indicated that the C677T polymorphism is not associated with CRC risk in Asian populations. Further investigations are needed to offer better insight into any role of this polymorphism in colorectal carcinogenesis.
Background: Many studies have investigated possible association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and ovarian cancer risk, but the impact is still unclear owing to the obvious inconsistencies. This study was performed to quantify the strength of the association with a metaanalysis. Methods: We searched the PubMed, Embase, and CNKI databases for studies relating the association between MTHFR C677T polymorphism and ovarian cancer risk and estimated summary odds ratios (ORs) with confidence intervals (CIs) for assessment. Results: Finally, eight studies with a total of 3,379 ovarian cancer cases and 4,078 controls were included into this meta-analysis. Overall the showed that MTHFR C677T polymorphism was not associated with ovarian cancer risk under all genetic models ($OR_{T\;versus\;C}$ = 1.03, 95%CI 0.90-1.18; $OR_{TT\;versus\;CC}$ = 1.08, 95%CI 0.79-1.47; $OR_{TT\;versus\;TC+CC}$ = 1.05, 95%CI 0.80-1.37; $OR_{TT+TC\;versus\;CC}$ = 1.05, 95%CI 0.86-1.21). Meta-analyses of studies with confirmation of HWE also showed no significant association. Subgroup analyses by ethnicity showed there was no significant association in the Caucasians but MTHFR C677T polymorphic variant T contributed to increased risk of ovarian cancer in East Asians. No evidence of publication bias was observed. Conclusion: Meta-analyses of available data show that MTHFR C677T polymorphism is not associated with ovarian cancer risk in Caucasians, but the MTHFR polymorphic variant T may contribute to increased risk in East Asians.
Objectives: The purpose of this study was to determine the relationship between methylation status of the Dact1 gene and MTHFR a1298c polymorphic forms in transitional cell carcinoma tissues in a Chinese population. Methods: Polymorphisms of folate metabolism enzyme gene MTHFR were assessed by restrictive fragment length polymorphism (RFLP) methods and PCR-based DNA methylation analysis was used to determine the CpG island methylation status of the Dact1 gene. Associations between the methylation status of the Dact1 gene and clinical characteristics, as well as MTHFR a1298c polymorphisms, were analyzed. Results: aberrant methylation of the Dact1 gene was found in 68.3% of cancer tissues and 12.4% of normal tissues,. The methylation rate of the Dact1 gene in cancer tissues was significantly higher in patients with lymph node metastasis than in those without lymph node metastasis (46.3% vs. 17.2%, P = 0.018). No association was found between aberrant DNA methylation and selected factors including sex, age, tobacco smoking, alcohol consumption and green tea consumption. After adjusting for potential confounding variables, variant allele of MTHFR a1298c was found to be associated with methylation of the Dact1 gene. Compared with wild type CC, the odds ratio was 4.33 (95% CI: 1.06-10.59) for AC and 4.95 (95% CI: 1.18-12.74) for AA. The N stage in TNM staging and the occurrence of lymph node metastasis were associated with an MTHFR 1298 AA+AC genotype (P<0.05). Conclusion: MTHFR 1298 AC and AA genotypes might help maintain a normal methylation status of the Dact1 gene, aberrant CpG island methylation of which is closely related to the genesis and progression of transitional cell carcinoma.
Background: Our objective was to evaluate the MTHFR C677T-A1298C polymorphisms in patients with breast cancer and in individuals with no history of cancer, to compare the levels of genetic damage and apoptosis under folic acid (FA) deficiency between patients and controls, and to assess associations with breast cancer. Methods: Genetic damage was marked by micronucleated binucleated cells (MNBN) and apoptosis was estimated by cytokinesis-block micronucleus assay (CBMN). PCR-RFLP molecular analysis was carried out. Results: The results showed significant associations between the MTHFR 677TT or the combined MTHFR C677T-A1298C and breast cancer risk (OR = 2.51, CI = 0.85 to 7.37, p = 0.08; OR = 4.11, CI = 0.78 to 21.8, p < 0.001). The MNBN from the combined MTHFR C677T-A1298C was higher and the apoptosis was lower than that of the single variants (p < 0.05). At 15 to 60 nmol/L FA, the MNBN in cases with the TTAC genotype was higher than controls (p < 0.05), whereas no significant difference in apoptosis was found between the cases and controls after excluding the genetic background. Conclusions: Associations between the combined MTHFR C677T-A1298C polymorphism and breast cancer are possible from this study. A dose of 120 nmol/L FA could enhance apoptosis in cases with MTHFR C677T-A1298C. Breast cancer individuals with the TTAC genotype may be more sensitive to the genotoxic effects of FA deficiency than controls.
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