• Korean Journal of Biological Psychiatry
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• v.12 no.2
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• pp.114-122
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• 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.

• Journal of Nutrition and Health
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• v.39 no.3
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• pp.264-273
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• 2006

Elevated maternal plasma homocysteine concentrations have been associated with adverse pregnancy outcomes. Serum homocysteine levels may be affected by the MTHFR genotypes and the nutritional status of B vitamins including vitamin $B_2,\;B_6$, folate and vitamin $B_{12}$. We investigated whether postnatal growth measurements were influenced by maternal MTHFR genotypes and their mid-pregnancy serum vitamin B and homocysteine levels. In 130 pregnant women of 24-28 wks of gestation, the MTHFR genotypes, serum B vitamins and homocysteine concentrations were analyzed. Physical growth status was assessed in their offsprings by measuring height, weight, and head and chest circumferences from birth up to 24 months. Serum homocysteine levels were higher in the subjects with T/T genotype than those with the C/T or C/C. Heights and head and chest circumferences of offsprings from the T/T mothers were significantly lower than those from the C/C or C/T mothers only when the serum homocysteine levels were above the median. The mean height of offsprings from the T/T mothers was significantly lower than those from the C/C and C/T mothers. The mean weight and head circumferences of offsprings born from the mothers whose mid-term pregnancy PLP levels were in the lowest quartile was significantly lower than those from mothers in the highest quartile. Heights and head circumferences of offsprings from the T/T mothers were significantly lower than those from the C/C or C/T mothers only when the serum FAD levels were in the lowest quartile. These results suggest that postnatal growth up to 24 months may be influenced by the maternal C677T MTHFR genotypes, and mid-pregnancy serum homocysteine and vitamin B status.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8093-8100
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• 2016

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.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1951-1955
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• 2013

Background: Associations between the methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism and esophageal cancer risk have been reported in many articles recently, but results were controversial. Therefore the present meta-analysis was conducted to to provide a more precise estimation. Methods: Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of associations. Results: Finally, six case-control studies involving a total of 1,302 cases and 2,391controls for the A1298C polymorphism were included. The meta-analysis showed that significantly increased risk for Asians (CC versus AA, OR=3.799, 95%CI=1.541-9.365, P=0.004; CCversusCA+AA, OR=3.997, 95%CI=1.614-9.900, P=0.003) and Caucasians (CC versus AA, OR=1.797, 95%CI=1.335-2.418, P=0.000; CC+CA versus AA,OR=1.240, 95%CI=1.031-1.492, P=0.022; CCversusCA+AA, OR=1.693, 95%CI=1.280-2.240, P=0.000). In addition, there was an association with risk for both ESCC (CC versus AA, OR=2.529, 95%CI=1.688-3.788, P=0.000; CCversusCA+AA, OR=2.572, 95%CI=1.761-3.758, P=0.000) and esophageal adenocarcinoma (EAC) (CC versus AA, OR=1.592, 95%CI=1.139-2.227, P=0.007; CC+CA versus AA,OR=1.247, 95%CI=1.016-1.530, P=0.035; CCversusCA+AA, OR=1.466, 95%CI=1.069-2.011, P=0.018). Conclusion: This meta-analysis suggested associations of the A1298C polymorphism with increased risk of esophageal cancer in both Asians and Caucasians. In addition, we found that the MTHFR A1298C polymorphism might influence risk ofESCC and EAC in the overall studies.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1203-1208
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• 2012

Background: Previous studies concerning the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and colorectal cancer risk in Asian populations generated conflicting results. A meta-analysis was therefore performed to allow a more reliable estimate of any link. Methods: Relevant studies concerning the association between the MTHFR C677T polymorphism and risk of colorectal cancer were included into this meta-analysis. The quality of the studies was assessed according to a predefined scale. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined for this gene-disease association using fixed or random effect models according to the heterogeneity between included studies. Results: Finally, 21 studies with a total of 6692 cases and 8266 controls were included. Meta-analyses showed that there was an obvious association of the MTHFR 677T allele with decreased risk of colorectal cancer (OR = 0.91, 95%CI=0.85-0.98, P=0.011). Subgroup analyses by country further identified this association, with dietary folate as the main source of heterogeneity. Conclusion: The MTHFR 677T allele is associated with a lower risk of colorectal cancer in Asian populations, and there is effect modification by population plasma folate.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1553-1556
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• 2012

Introduction: Antimetabolites may cause severe toxicity and even toxic death in cancer patients. Our aim was to evaluate the relationship between antimetabolite toxicity and pharmacogenetics in patients with severe clinical toxicity or alanine transaminase (ALT) elevation after fluorouracil (5FU), capecitabine or methotrexate administration. Patients and Methods: Cancer patients with severe antimetabolite toxicity were evaluated for methylenetetrahydrofolate reductase (MTHFR) gene C667T, thymidilate synthase (TS) gene 5´UTR variable number of tandem repeats (VNTR), dihydroprymidine dehydrogenase (DPYD) gene IVS14+1G/A, Xeroderma pigmentosum (XPD) gene Lys751Gln and X-ray repair cross-complementing group 1 (XRCC1) gene Arg399Gln polymorphisms. Results: Eighteen patients were enrolled, with a male/female ratio of 0.8. They had osteosarcoma in methotrexate group (n=7), gastrointestinal malignancies in 5FU group (n=9) and breast cancer in the capecitabine group (n=2). Mucositis and dermatitis occurred in all groups, together with ALT elevation in the methotrexate group and 2 toxic deaths were encountered. DPYD, TS, MTHFR, XPD and XRCC1 gene polymorphism rare allele frequencies were observed to be higher than in the general population. Conclusion: Pharmacogenetics might contribute to tailored therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3943-3947
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• 2012

Objective: Findings for associations between the methylenetetrahydrofolate reductase (MTHFR) A1298C gene polymorphism and head and neck cancer risk have been conflicting. We therefore performed a meta-analysis to derive a more precise relationship. Methods: Ten published case-control studies were collected and odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between MTHFR A1298C polymorphism and head and neck cancer risk. Sensitivity analysis and publication bias assessment also were performed to guarantee the statistical power. Results: Overall, no significant association between MTHFR A1298C polymorphism and head and neck cancer risk was found in this meta-analysis (C vs. A: OR=1.04, 95%CI=0.87-1.25, P=0.668, Pheterogeneity<0.001; CC vs. AA: OR=1.07, 95%CI=0.70-1.65, P=0.748, $P_{heterogeneity}<0.001$; AC vs. AA: OR=1.06, 95%CI=0.88-1.27, P=0.565, $P_{heterogeneity}<0.001$; CC+AC vs. AA: OR=1.06, 95%CI=0.86-1.30, P=0.571, $P_{heterogeneity}<0.001$; CC vs. AA+AC: OR=1.02, 95%CI=0.69-1.52, P=0.910, $P_{heterogeneity}<0.001$). Similar results were also been found in succeeding analysis of HWE and stratified analysis of ethnicity. Conclusion: In conclusion, our meta-analysis demonstrates that MTHFR A1298C polymorphism may not be a risk factor for developing head and neck cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3937-3942
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• 2012

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.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2249-2252
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• 2012

Objective: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been reported to be associated with pancreatic cancer, but the published studies had yielded inconsistent results.We therefore performed the present meta-analysis. Methods: A search of Google scholar, PubMed, Cochrane Library and CNKI databases before April 2012 was conducted to summarize associations of MTHFR polymorphisms with pancreatic cancer risk. Assessment was with odds ratios (ORs) and 95% confidence intervals (CIs). Publication bias were also calculated. Results: Four relative studies on MTHFR gene polymorphisms (C667T and A1298C) were involved in this meta-analysis. Overall, C667T(TT vs. CC : OR = 1.61, 95%CI = 0.78 - 3.34; TT vs. CT : OR = 1.41, 95%CI = 0.88-2.25; dominant model: OR = 0.68, 95%CI = 0.40-1.17; recessive model: OR = 0.82, 95%CI = 0.52-1.30) and A1298C(CC vs. AA:OR=1.01, 95%CI=0.47-2.17; CC vs. AC: OR=0.99,95%CI=0.46-2.14; dominant model: OR=1.01, 95%CI = 0.47-2.20; recessive model: OR = 1.01, 95%CI = 0.80-1.26) did not increase pancreatic cancer risk. Conclusion: This meta-analysis indicated that MTHFR polymorphisms (C667T and A1298C) were not associated with pancreatic cancer risk.

• Journal of Animal Science and Technology
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• v.54 no.3
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• pp.157-163
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• 2012

The male reproduction is precisely controlled by a number of intrinsic and extrinsic factors. These factors usually involve in expressional regulation of various molecules influencing on sperm production in the testis. A number of ways are employed to control the transcription of specific genes, including epigenetic modifications of DNA and histone molecules. DNA methylation of CpG dinucleotides is a commonly used regulatory mechanism for testicular genes associated with the fertility. Previous studies have demonstrated the infertility induced by improper DNA methylation of these genes. In the present research, we attempted to determine transcriptional expression of some of these genes in the rat testis at different postnatal ages using real-time PCR analysis. These genes include neurotrophin 3 (Ntf3), insulin-like growth factor II (Igf2), JmjC-domain-containing histone demethylase 2A 1 (Jhm2da), paired box 8 transcription factor (Pax8), small nuclear ribonucleoprotein polypeptide N (Snrpn), and 5,10-methylenetetrahydrofolate reductase (Mthfr). The expression levels of Ntf3, Igf2, and Snrpn genes were the highest at the neonatal age, followed by transient decreases at the prepubertal age. Expression of Jhm2da and Mthfr genes were continuously increased from the neonate to 1 year of age. The levels of Pax8 mRNA at the early ages were higher than those at the later ages of postnatal development. These findings suggest that expression of some fertility-associated testicular genes in the rat during postnatal period could be differentially regulated by the control of the degree of DNA methylation.