• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.10
• /
• pp.5069-5074
• /
• 2012

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.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.6
• /
• pp.2597-2604
• /
• 2012

Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme involved in folate metabolism; a single nucleotide polymorphism (SNP) C677T has been reported to be linked with altered incidences of several diseases. We here conducted a meta-analysis of 15 published epidemiological studies with a total of 7306 cases and 8062 controls to evaluate its association with prostate cancer risk with overall and subgroup analyses. No statistical relationship was found overall with any genetic model (TT vs. CC: OR = 0.80, 95%CI = [0.62, 1.04], P = 0.094; CT vs. CC: OR = 0.97, 95%CI = [0.84; 1.12], P = 0.667; Dominant: OR = 0.94, 95%CI = [0.82; 1.07], P = 0.343; Recessive: OR = 0.81, 95%CI = [0.64; 1.04], P = 0.104), but after the exclusion of several studies, we could observe the homozygote TT to confer less susceptibility to prostate cancer in carriers; moreover, different effects of the polymorphism on prostate cancer risk was detected from subgroup analysis stratified by participants' residential region: significant reduced prostate cancer risk was found to be associated with the polymorphism from Asian studies (TT vs. CC: OR = 0.47, 95%CI = [0.33; 0.67], P < 0.001; CT vs. CC: OR = 0.73, 95%CI = [0.60; 0.90], P = 0.002; Dominant: OR = 0.67, 95%CI = [0.56; 0.82], P < 0.001; Recessive: OR = 0.55, 95%CI = [0.40; 0.76], P < 0.001) while studies from Europe indicated a slight increased risk under dominant model with marginal significance (OR = 1.14, 95%CI = [0.99; 1.30], P = 0.064). Moreover, the protective effect of the polymorphism against prostate cancer was also shown by studies performed in yellow Asians (TT vs. CC: OR = 0.48, 95%CI = [0.31; 0.75], P = 0.001; CT vs. CC: OR = 0.68, 95%CI = [0.51; 0.90], P = 0.006; Dominant: OR = 0.63, 95%CI = [0.48; 0.82], P < 0.001; Recessive: OR = 0.57, 95%CI = [0.39; 0.84], P = 0.004). We propose that these phenomena should be viewed with the consideration of folate metabolism profile and different gene background as well as living habits of different populations, and more relevant studies should be conducted to confirm our hypothesis and provide a comprehensive and clear picture concerning this topic.

• Animal Bioscience
• /
• v.34 no.6
• /
• pp.975-984
• /
• 2021

Objective: Inbreeding depression of reproduction is a major concern in the conservation of native chicken genetic resources. Here, based on the successful development of strongly inbred (Sinb) and weakly inbred (Winb) Langshan chickens, we aimed to evaluate inbreeding effects on reproductive traits and identify candidate genes involved in inbreeding depression of reproduction in Langshan chickens. Methods: A two-sample t-test was performed to estimate the differences in phenotypic values of reproductive traits between Sinb and Winb chicken groups. Three healthy chickens with reproductive trait values around the group mean values were selected from each of the groups. Differences in ovarian and hypothalamus transcriptomes between the two groups of chickens were analyzed by RNA sequencing (RNA-Seq). Results: The Sinb chicken group showed an obvious inbreeding depression in reproduction, especially for traits of age at the first egg and egg number at 300 days (p<0.01). Furthermore, 68 and 618 differentially expressed genes (DEGs) were obtained in the hypothalamus and ovary between the two chicken groups, respectively. In the hypothalamus, DEGs were mainly enriched in the pathways related to vitamin metabolism, signal transduction and development of the reproductive system, such as the riboflavin metabolism, Wnt signaling pathway, extracellular matrix-receptor interaction and focal adhesion pathways, including stimulated by retinoic acid 6, serpin family F member 1, secreted frizzled related protein 2, Wnt family member 6, and frizzled class receptor 4 genes. In the ovary, DEGs were significantly enriched in pathways associated with basic metabolism, including amino acid metabolism, oxidative phosphorylation, and glycosaminoglycan degradation. A series of key DEGs involved in folate biosynthesis (gamma-glutamyl hydrolase, guanosine triphosphate cyclohydrolase 1), oocyte meiosis and ovarian function (cytoplasmic polyadenylation element binding protein 1, structural maintenance of chromosomes 1B, and speedy/RINGO cell cycle regulator family member A), spermatogenesis and male fertility (prostaglandin D2 synthase 21 kDa), Mov10 RISC complex RNA helicase like 1, and deuterosome assembly protein 1) were identified, and these may play important roles in inbreeding depression in reproduction. Conclusion: The results improve our understanding of the regulatory mechanisms underlying inbreeding depression in chicken reproduction and provide a theoretical basis for the conservation of species resources.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.5
• /
• pp.2193-2197
• /
• 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.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.5
• /
• pp.3163-3168
• /
• 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.

• Clinical and Experimental Reproductive Medicine
• /
• v.46 no.3
• /
• pp.107-111
• /
• 2019

Objective: Spermatogenesis is a complex process that is regulated by a number of genes, some of which are involved in folate-dependent 1-carbon metabolism. Methionine synthase (encoded by MTR) is a key enzyme participating in this pathway. This study aimed to investigate the relationship of the MTR 2756A > G polymorphism with idiopathic male fertility in the Iranian population. Methods: The participants of this study included 100 men with idiopathic infertility and 100 healthy men as the control group. Genotyping of MTR 2756A > G was performed using the polymerase chain reaction and restriction fragment length polymorphism technique. The obtained data were analyzed using SPSS ver. 20.0 with a level of confidence of p< 0.05. Results: The frequencies of the A and G alleles at this locus were 77% and 23% in infertile patients and 84% and 16% in the control group, respectively. The frequencies of the GG, GA, and AA genotypes were 5%, 36%, and 59% in the infertile patients versus 3%, 27%, and 70% in the control group, respectively. No significant difference was observed in any genetic models. Conclusion: In general, the findings of this study suggest that the MTR 2756A > G single-nucleotide polymorphism is not a predisposing factor for idiopathic infertility in men.

• Korean Journal of Community Nutrition
• /
• v.10 no.4
• /
• pp.525-535
• /
• 2005

This study was conducted to investigate the effect of a 3 week low calorie diet (LCD) and a 9 week of behavior modification (BM) program on the weight loss, mineral and vitamin status in 22 obese women. The subject were healthy, obese (PIBW> $120\%$) women aged 20 - 50 Yr and not taking any medications known to influence body composition, mineral or vitamin metabolism During the LCD program, subjects were provided commercial liquid formulas with 125 kcal per pack and were instructed to have a formula for replacement of one meal and at least one regular meal per day within the range of daily 800 - 1200 kcal intake. During the BM program the subjects weekly attended the group nutrition counseling session to encourage themselves to modify their eating behavior and spontaneously restrict their energy intakes. The BM program focused on stimulus control, control of portion sizes and modification of binge eating and other adverse habits. The initial mean energy intake of subjects was 2016.9 $\pm$ 129.8 kcal ($100.8\%$ of RDA) and dropped to 1276.5 $\pm$ 435.7 kcal at the end of a 3 week of LCD program and elevated to 1762 $\pm$ 329.3 kcal at the end of a 9 week of BM program. Carbohydrate, protein and fat intakes were significantly decreased at the end of the LCD but carbohydrate was the only macro nutrient that showed significant decrease (p < 0.05) at the end of the BM program compared to baseline. Calcium and iron intakes decreased significantly (p < 0.01, respectively) with no significant changes in other micronutrients at the end of the LCD. The mean weight of the subjects decreased from 73.8 $\pm$ 8.0 kg to 69.2 $\pm$ 7.7 kg with LCD and ended up with 67.7 $\pm$ 7.1 kg after 9 weeks of BM. The 3 weeks of LCD reduced most of the anthropometric indices such as BMI, PIBW, fat weight, wast-to-hip ratio and subscapular and suprailiac skinfold thickness. The 9 weeks of behavior modification showed slight change or maintenance of each anthropometric measurements. Weight loss and decreased WHR with the diet program induced significantly decreased systolic blood pressure. SGOT, SGPT and serum insulin levels with improved serum lipid profiles. Biochemical parameters related to iron status such as hemoglobin, hematocrit were significantly decreased (p < 0.01) at the end of the LCD. But their mean values were within normal range. The mean serum 25 (OH) vitamin $D_3$ level significantly increased after whole diet program. Serum folate level significantly decreased after 12 weeks of diet program. In conclusion 3 weeks of LCD brought 4.6 kg reduction in body weight without risk of iron, zinc or vitamin D deficiency and 9 weeks of the BM was effective to maintain nutritional status with slightly more weight reduction (1.5 kg). However calcium intake and serum folate should be monitored during the LCD and BM because of increased risk of deficiencies.

• Clinical and Experimental Reproductive Medicine
• /
• v.44 no.3
• /
• pp.152-158
• /
• 2017

Objective: To identify the associations between polymorphisms of the 3'-untranslated region (UTR) of methylenetetrahydrofolate reductase (MTHFR) gene, which codes for an important regulatory enzyme primarily involved in folate metabolism, and idiopathic recurrent pregnancy loss (RPL) in Korean women. Methods: The study population comprised 369 RPL patients and 228 controls. MTHFR 2572C > A, 4869C > G, 5488C > T, and 6685T > C 3'-UTR polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis or by TaqMan allelic discrimination assays. Natural killer cell proportions were determined by flow cytometry. Results: The MTHFR 2572-5488-6685 (A-C-T) haplotype had an adjusted odds ratio of 0.420 (95% confidence interval, 0.178-0.994; p= 0.048) for RPL. Analysis of variance revealed that MTHFR 4869C > G was associated with altered $CD56^+$ natural killer cell percentages (CC, $17.91%{\pm}8.04%$; CG, $12.67%{\pm}4.64%$; p= 0.024) and folate levels (CC, $12.01{\pm}7.18mg/mL$; CG, $22.15{\pm}26.25mg/mL$; p= 0.006). Conclusion: Variants in the 3'-UTR of MTHFR are potential biomarkers for RPL. However, these results should be validated in additional studies of ethnically diverse groups of patients.

• Asian-Australasian Journal of Animal Sciences
• /
• v.25 no.10
• /
• pp.1481-1492
• /
• 2012

The interaction of the genes involved in intestinal development is the molecular basis of the regulatory mechanisms of intestinal development. The objective of this study was to identify the significant pathways and key genes that regulate intestinal development in Landrace piglets, and elucidate their rules of operation. The differential expression of genes related to intestinal development during suckling time was investigated using a porcine genome array. Time sequence profiles were analyzed for the differentially expressed genes to obtain significant expression profiles. Subsequently, the most significant profiles were assayed using Gene Ontology categories, pathway analysis, network analysis, and analysis of gene co-expression to unveil the main biological processes, the significant pathways, and the effective genes, respectively. In addition, quantitative real-time PCR was carried out to verify the reliability of the results of the analysis of the array. The results showed that more than 8000 differential expression transcripts were identified using microarray technology. Among the 30 significant obtained model profiles, profiles 66 and 13 were the most significant. Analysis of profiles 66 and 13 indicated that they were mainly involved in immunity, metabolism, and cell division or proliferation. Among the most effective genes in these two profiles, CN161469, which is similar to methylcrotonoyl-Coenzyme A carboxylase 2 (beta), and U89949.1, which encodes a folate binding protein, had a crucial influence on the co-expression network.

• Journal of Life Science
• /
• v.18 no.8
• /
• pp.1036-1041
• /
• 2008

Methenyltetrahydrofolate synthetase extract was obtained from mouse liver and purified via $30{\sim}70%$ ammonium sulfate fractionation, Fast Q anion exchange and phenyl agarose chromatography. HPLC gel chromatography and SDS-polyacrylamide electrophoresis experiments showed that the enzyme is a monomer with molecular weight of 23 kDa. Optimum temperature and pH were $35^{\circ}C$ and 6.5, respectively. The enzyme was chemically modified only by tetranitromethane and 1-ethyl-3- (3-dimethyl aminopropyl)-carbodiimide (EDC), indicating that tyrosine and carboxylate are in the active site. pH studies showed that 2 tyrosines are involved in the binding of the substrates and a carboxylate in catalysis. Therefore, the chemical mechanism of the enzyme is likely that 2 tyrosines bind to ATP and 5-formylTHFand a carboxylate acts as a general base.