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Through summarizing and analyzing a large number of documents and reports of large academic conferences in China, the current situation and the prospect of individualized drug delivery model were analyzed based on folate metabolic gene in pharmaceutical care. Folate metabolic genemethylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G were related with development of multiple diseases. Its polymorphism guidesindividualized drug administrationto increase the efficacy of drugs or decrease adverse effects.
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Autism is a neurodevelopmental disorders that manifests before 3 years of age, more common in boys. Whereas causes of autism remain uncertain, it is influenced by genetic and environmental factors. Recent studies have shown that the genes involved in the folate metabolism pathway may play an important role in autism. Methionine synthase reductase (MTRR) is a key enzyme that plays an important role in the homocysteine/folate metabolism and has been shown to be implicated in neurological disorders including autism. In this study, 356 subjects were studied, which consists of 142 autistic children and 214 nonautistic control. Genomic DNA was extracted from blood samples. Genotype of MTRR 66A>G gene was performed using polymerase chain reaction-allele specific PCR (AS-PCR). The genotype frequencies of AA, AG and GG in the children with autism were 9.9%, 76.0% and 14.1%, respectively and in control group were 13.1%, 86.0% and 0.9%, respectively. The allele frequencies of A, G in the children with autism were 48.0%, 52.0%, respectively and in control group were 56.0%, 44.0%, respectively. Statistical analysis showed that there is a significant correlation in the genotype between two groups (OR=20, 95% CI=4.1 to 98, P<0.001). It is concluded that MTRR A66G polymorphism is associated with autism in a population in northern Iran. More studies with larger number should be done to confirm this result.
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Autistic DisorderABSTRACT
Objectives To investigate the relationship of methylenetetrahydrofolate reductase (MTHFR) and methioninesynthase reductase (MTRR) with unexplained recurrent spontaneous abortion (URSA). Methods Case control study was used to select 244 patients with URSA (miscarriage group) and 116 normal women (control group) who were admitted to Tianjin Medical University General Hospital and Tianjin Women’s and Children’s Health Center from January 2013 to March 2015. The oral mucosal epithelial cells were extracted using fluorescence quantitative PCR to detect MTHFR gene C677T, A1298C and MTRR gene loci of A66G single nucleotide polymorphisms (SNP). The relationship between folate metabolism related gene polymorphisms of MTHFR and MTRR and URSA was analysed. Results The frequency of C677T genotype MTHFR was significantly higher in URSA group than that in the control group, and the frequency of CT genotype was significantly lower than that of the control group (P<0.05). There was no significant difference in the frequencies of A1298C MTRR and A66G MTHFR between the two groups. The activity of MTHFR, red cell folate and plasma folate levels were significantly lower in URSA group than those of control group. Homocysteine levels were significantly higher in URSA group than those of control group (P<0.05). There were no significant differences in serum folic acid, red cell folate, homocysteine cysteine levels between patients <35 years old and ≥ 35 years old in URSA group. Conclusion C677TMTHFR gene polymorphism is associated with unexplained recurrent spontaneous abortion.
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Objective To explore the genotype distribution of methylenetetrahydrofolate reductase ( MTH-FR)C677T,A1298C and methionine synthase reductase (MTRR) A66G involved in the folic acid biosynthetic path-way among Chinese Han gestational age women in Sanhe City .Methods 601 samples were recruited from Sanhe re-gion,genomic DNA was obtained from the oral mucosa cells .The detections of MTHFR and MTRR gene polymor-phisms conducted with Taqman -MGB technology .The distribution of gene polymorphisms of this study was analyzed and compared with partial regions of China ,which were reported.Results The frequency of MTHFR 677TT among Sanhe women(37.40%) was significantly different to Yanbian (28.30%),Zhenjiang(21.84%),Songzi(15.40%), Deyang(13.80%),Huizhou(10.90%),Qionghai(6.14%),Zibo(43.6%) (χ2 =12.60,87.44,151.95,233.02, 61.87,446.90,7.27,all P<0.05).The frequency of MTHFR 1298CC(2.30%) was significantly different to Zibo (1.44%),Zhenjiang(3.50%),Songzi(2.60%),Deyang(6.26%),Huizhou(7.20%),Qionghai(7.13%) (χ2 =5.84,6.49,14.32,32.54,22.94,53.12,all P<0.05).The frequency of MTRR 66GG (7.50%) was significantly different to Qionghai (9.25%),Songzi(6.40%)(χ2 =16.34,4.10,all P<0.05).Conclusion The MTHFR, MTRR polymorphism distribution of Han women in Sanhe City is region specific ,respective .
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Objective To analyze the relationship between methylenetetrahydrofolate reductase (MTHFR)C677T,A1298C and methionine synthase reductase(MTRR)gene polymorphism with abnormal pregnancy history.Methods 549 normal women (control group)and 300 women with the abnormal pregnancy history(observation group)were taken as the subjects by adopting the case control research method.The oral mucosa epithelial cells were collected for extracting genomic DNA.The MTHFR and MTRR gene polymorphisms were detected by the gene sequencing method.Results The distribution frequency of MTHFR 677TT genotype in the abnormal pregnancy group was significantly increased compared with the control group (10.00% vs.3.46%,χ2 =15.25,P <0.01);the distribution frequency of MTHFR-1298CC genotype in the abnormal pregnancy group was significantly in-creased compared with the control group (11.00 vs.4.01%,χ2 =15.66,P <0.01);the distribution frequency of MTRR A66G gen-otype had no statistical difference between the two groups(χ2 =3.02,P =0.082).The interactive analysis of 2 genes indicated that simultaneous carrying the MTHFR A1298C mutation site and MTRR A66G mutation site increased the possibility of abnormal pregnancy occurrence (OR=1.52,P =0.011).Conclusion MTHFR C677T and A1298C have a certain correlation with female ab-normal pregnancy occurrence.
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Objective To explore the 5,10-methylenetetrahydrofolate reductase (MTHFR) and 5-methyltetrahydro-folate-homocysteine methyltransferase reductase ( MTRR ) gene polymorphisms among the Han women in Zhangjiagang city .Methods A total of 4008 Han women were recruited .Their oral epithelial cells were collected to extract genome DNA in order to detect gene polymorphisms of MTHFR and MTRR using fluorescence quantitative PCR.Then the results were compared with those in other cities in China .Results The genotype frequencies of MTHFR C677T CC, CT and TT among Zhangjiagang women are 32.2%, 49.5%and 18.3%, respectively.The C allele frequency is 64.3%, T allele frequency is 35.7%.The genotype frequencies of MTHFR A1298 C AA, AC and CC are 68.7%,28.7% and 2.5%, respectively .The A allele frequency is 80.8%, C allele frequency is 19.2%.The genotype frequencies of MTRR A66 G AA, AG and GG are 54.4%, 38.5%and 7.1%, respectively . The A allele frequency is 76.3%, G allele frequency is 26.4%.Conclusions The MTHFR, MTRR polymorphism distribution of Han women in Zhangjiagang city is region specific.
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Objective To investigate the relationship of plasma homocysteine with the genotype distribution of MTHFR and MTRR among Chinese Han women in Xiangtan. Methods MTHFR C677T, A1298C and MTRR A66G geno?typing was analyzed to detect the distribution of gene polymorphisms among 1 701 women from Xiangtan city then the data were compared with the rest of the Han women in Zibo, Zhengzhou, Yantai, Zhenjiang, Songzi, Huizhou, Qionghai. Plasma Hcy levels from 110 patients were measured and analyzed the correlation with gene polymorphisms. Results The frequency of MTHFR C677T genotype and allele frequencies in Xiangtan is 12.6%which is higher than Huizhou (10.9%) and Qionghai (6.1%) but lower than Zibo (43.6%), Zhengzhou (36.8%), Yantai (32.2%), Zhenjiang (21.8%) with statistically significant dif?ference (P<0.05). There is no significant different in MTHFR C677T between Xiangtan and Songzi. The frequency of MTH?FR A1298C genotype and allele frequencies in Xiangtan is 4.8%which is lower than Qionghai(7.1%)but higher than Zibo (1.4%),Zhengzhou(2.4%), Yantai(1.8%), Zhenjiang(3.5%)and Songzi(2.6%)with statistically significant difference. The frenquency of MTRR A66G genotype and allele frequencies in Xiangtan is 6.8%which is higher than Zibo (4.8%) but lower than Qionghai (9.3%) with statistically signifcant difference. Plasma Hcy concentration correlate with MTHFR C677T, Hcy concentration in TT population is higher than that in CT and CC population(μmol/L:8.52±2.01 vs 5.94±1.47 vs 5.71± 0.18);Plasma Hcy concentration also correlate with MTHFR A1298C and Hcy concentration in CC population is higher than AA and AC population(μmol/L:9.83 ± 2.26 vs 6.35 ± 2.13 vs 5.55 ± 1.75);Plasma Hcy concentration does not correlate with MTRR A66G. Conclusion The gene polymorphism of MTHFR C677T, A1298C and MTRR A66G among the Han women in Xiangtan was statistically different from other selected regions of China. Mutation in MTHFR C 677T and A1298C were associated with elevated plasma levels of Hcy.
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BACKGROUND AND OBJECTIVES: Methionine synthase reductase (MTRR) is a vital enzyme of homocysteine/methionine metabolic pathway and is required for the conversion of inactive form of methionine synthase (MTR) to its active form. A clinically important allelic variant of MTRR A66G, with less enzymatic activity is reported with worldwide prevalence rate of ~ 30%. The present study was designed to determine the frequency of MTRR A66G polymorphism in rural Sunni Muslim population of Eastern Uttar Pradesh. MATERIALS AND METHODS: Total 56 subjects were analyzed for MTRR A66G polymorphism. A66G mutation analysis was carried out according to the polymerase chain reaction-restriction fragment length polymorphism method of Wilson et al. [1] amplification with MTRR specific primers followed by amplicon digestion with NdeI enzyme was used for the identification of different MTRR genotypes in subjects. RESULTS AND DISCUSSION: The AA genotype was found in 5 subjects, AG in 23 subjects, and GG genotype in 28 subjects. Genotype frequencies of AA, AG, and GG were 0.089, 0.41, and 0.5 respectively. The allele frequency of A allele was found to be 0.298 and G allele was 0.705. CONCLUSION: It is evident from the present study that the percentage of homozygous genotype GG and frequency of G allele is high in the target Muslim population.
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Adolescent , Adult , Aged , Alleles , Codes of Ethics , Ethics , Ferredoxin-NADP Reductase/genetics , Gene Frequency , Genetic Predisposition to Disease , Genotype , India , Islam , Humans , Middle Aged , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Population Groups/geneticsABSTRACT
Objective: This study was aimed to evaluate the Methionine synthase reductase (MTRR) A66G mutation in Yadav and Scheduled Caste (SC) population of Uttar Pradesh. Materials and Methods: Blood samples were collected from 100 subjects after taking informed written consent and PCR-RFLP method was used for the analysis of A66G mutation. After NdeI digestion, 66-bp amplicon of normal allele was cut into 22- and 44-bp long fragments, whereas mutant G allele was not digested. Results: Frequencies of genotypes in Yadav population AA, AG, and GG were 12%, 60%, and 28%, respectively, and in SC population, genotypic frequencies were 12% (AA), 52% (AG), and 36% (GG). Conclusion: MTRR gene A66G mutation is found to be polymorphic in both the target populations with G allele frequencies being 0.58 for Yadav and 0.62 for Scheduled Caste.
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Gastric cancer is ranked as the most common cancer in Koreans. A recent molecular biological study about the folate pathway gene revealed the correlation with a couple of cancer types. In the folate pathway, several genes are involved, including methylenetetrahydrofolate reductase (MTHFR), methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR), and methyltetrahydrofolate-homocysteine methyltransferase (MTR). The MTHFR gene has been reported several times for the correlation with gastric cancer risk. However, the association of the MTRR or MTR gene has not been reported to date. In this study, we investigated the association between the single nucleotide polymorphisms (SNPs) of the MTHFR, MTRR, and MTR genes and the risk of gastric cancer in Koreans. To identify the genetic association with gastric cancer, we selected 17 SNPs sites in folate pathway-associated genes of MTHFR, MTR, and MTRR and tested in 1,261 gastric cancer patients and 375 healthy controls. By genotype analysis, estimating odds ratios and 95% confidence intervals (CI), rs1801394 in the MTRR gene showed increased risk for gastric cacner, with statistical significance both in the codominant model (odds ratio [OR], 1.39; 95% CI, 1.04 to 1.85) and dominant model (OR, 1.34; 95% CI, 1.02 to 1.75). Especially, in the obese group (body mass index > or = 25 kg/m2), the codominant (OR, 9.08; 95% CI, 1.01 to 94.59) and recessive model (OR, 3.72; 95% CI, 0.92 to 16.59) showed dramatically increased risk (p < 0.05). In conclusion, rs1801394 in the MTRR gene is associated with gastric cancer risk, and its functional significance need to be validated.
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Humans , 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase , Ferredoxin-NADP Reductase , Folic Acid , Genotype , Methylenetetrahydrofolate Reductase (NADPH2) , Odds Ratio , Oxidoreductases , Polymorphism, Single Nucleotide , Stomach NeoplasmsABSTRACT
PURPOSE: Aneuploidy is the cause of diseases such as Down syndrome or Edward syndrome and, more generally, is a major cause of mental retardation and fetal loss. The purpose of this study was to evaluate the association between MTHFR (C677T) or MTRR (A66G) polymorphisms and fetal aneuploidy. MATERIALS AND METHODS: Data was collected from 37 women who had a fetus with aneuploidy (cases) and 78 women who had previously delivered at least two healthy children without aneuploidy and did not have a history of miscarriage or abnormal pregnancy (controls). The MTHFR (C677T) or MTRR (A66G) polymorphisms were analyzed by PCR-restriction fragment length polymorphism assay. RESULTS: The frequencies of the MTHFR 677 CC, CT, and TT genotypes were 30.7%, 48.7%, and 20.6% in the control group and 37.8%, 48.6%, and 13.5% in the case group, respectively. There were no significant differences in genotype frequencies between the two groups. For the MTRR A66G polymorphism, the frequencies of the AA, AG and GG genotypes were 50%, 46.1%, and 3.9% in the control group and 13.5%, 81.1%, and 5.4% in case group, respectively. The frequency of the MTRR AG mutant was significantly increased in the case group, with an odds ratio of 6.5 (95% CI: 2.3-18.6, P<0.05). CONCLUSION: The results of this study suggest that mother carriers with the MTRR G allele have an increased risk of fetal aneuploidy, while the MTHFR T allele is not associated with increased risk of fetal aneuploidy. The MTRR A66G polymorphism may be a risk factor for producing a child with chromosomal aneuploidy.
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Child , Female , Humans , Pregnancy , 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase , Abortion, Spontaneous , Alleles , Aneuploidy , Down Syndrome , Ferredoxin-NADP Reductase , Fetus , Genotype , Intellectual Disability , Methionine , Mothers , Odds Ratio , Oxidoreductases , Risk FactorsABSTRACT
Homocysteine (Hcy) is thought to play an important role in the development of osteoporosis and fracture. Methionine synthase reductase (MTRR) is an enzyme involved in the conversion of Hcy to methionine. We hypothesized that certain genetic polymorphisms of MTRR leading to reduced enzyme activity may cause hyperhomocysteinemia and affect bone metabolism. We therefore examined the associations of the A66G and C524T polymorphisms of the MTRR gene with bone mineral density (BMD) and serum osteocalcin levels in postmenopausal women. Although we did not detect any significant associations between MTRR polymorphisms and BMD or serum osteocalcin levels, we found that the 66G/524C haplotype, which has reduced enzyme activity, was significantly associated with serum osteocalcin levels in a gene-dose dependent manner (P=0.002). That is, the highest osteocalcin levels (34.5+/-16.8 ng/ml) were observed in subjects bearing two copies, intermediate osteocalcin levels (32.6+/-14.4 ng/ml) were observed in subjects bearing one copy, and the lowest levels of osteocalcin (28.8+/-10.9 ng/ml) were observed in subjects bearing no copies. These results suggest that the 66G/524C haplotype of the MTRR gene affect bone turn over rate.