scholarly journals The Allele Frequencies of Three Polymorphisms in Genes Involved in Homocysteine Metabolism in a Group of Unrelated Healthy Singaporeans

2010 ◽  
Vol 29 (2) ◽  
pp. 111-119 ◽  
Author(s):  
Chuanfei Chen ◽  
Yik-Yuen Gan
Keyword(s):  
Genetic Risk ◽  
Total Population ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr C677t ◽  
Allele Frequencies ◽  
Methionine Synthase ◽  
Asian Populations ◽  
Insertion Allele ◽  
677T Allele ◽  
Ms A2756g

The cystathionineβ-synthase (CBS) 844ins68 polymorphism, methionine synthase (MS) A2756G SNP, and 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T SNP are associated with homocysteine (Hcy) level in humans. Elevated Hcy level is considered a risk factor for atherosclerotic diseases among Asian populations. Therefore, the three polymorphisms may vary the risk for developing such diseases in Singaporeans. In this study, the three polymorphisms were determined in a group of unrelated healthy Singaporeans (273 Chinese, 127 Indians, and 156 Malays). Regarding allele frequencies, Indians had the highest frequencies of the CBS insertion allele (2.0%) and the MS 2756G allele (26.4%), while Chinese had the highestMTHFR677T allele frequency (27.5%). In addition, theMTHFR677T allele was found significantly lower in Chinese males than in their female counterparts. As the CBS insertion allele was suggested to be associated with lower Hcy level, whereas the MS 2756G allele and theMTHFRT/T genotype were related to higher Hcy level, the MS A/G or G/G genotype and theMTHFRT/T genotype were considered double genetic risk factors for elevated Hcy level. The frequency of such double genetic risk was 0.7% (4 subjects) in the total population consisting of 3 Chinese (1.1%) and 1 Malays (0.6%). NoMTHFRT/T genotype was found in Indians. Such results suggested that Chinese could have higher Hcy levels than Malays while the situation for Indians was complicated. Since human Hcy levels are also affected by environmental factors, further studies are required to better evaluate the association between these three polymorphisms and Hcy levels and/or disease susceptibilities in Singaporeans.

scholarly journals 3’UTR Polymorphism of Thymidylate Synthase gene increased the risk of persistence of pre-neoplastic cervical lesions

2020 ◽  
Author(s):  
Nayara Nascimento Toledo Silva ◽  
Ana Carolina Silva Santos ◽  
Verlândia Mendes Nogueira ◽  
Cláudia Martins Carneiro ◽  
Angelica Alves Lima
Keyword(s):  
Thymidylate Synthase ◽  
Carbon Metabolism ◽  
Mthfr C677t ◽  
Methionine Synthase ◽  
Cervical Carcinogenesis ◽  
Cervical Lesions ◽  
Neoplastic Lesions ◽  
One Carbon Metabolism ◽  
Ms A2756g

Abstract Background: Cervical cancer is caused by high-risk Human Papillomavirus (hr-HPV) infection associated with cofactors that has been analyzed as predictors of the remission or persistence of cytological abnormalities remission or persistence. These cofactors can be either environmental, epigenetic, or genetic. Polymorphism in genes of enzymes that act on one-carbon metabolism alter their activity and also may be associated with cervical carcinogenesis because they affect DNA synthesis and repair, and gene expression. Therefore, this study aimed to analyze the risk of persistence of pre-neoplastic cervical lesions according to genetic polymorphisms involved in one-carbon metabolism. Methods: Our sample consisted of 106 women, divided into two groups – Remission (n=60), i.e., with the presence of pre-neoplastic lesions at first meeting (T1) and normal cytology after six months of follow-up (T2), and Persistence (n=46), i.e., with the presence of pre-neoplastic lesions at T1 and T2. We obtained cervical samples for cytological analysis (T1 and T2), HPV detection (T1), and evaluation of polymorphism C667T of Methylenetetrahydrofolate Reductase (MTHFR C677T), A2756G of Methionine Synthase (MS A2756G), A66G of Methionine Synthase Reductase (MTRR A66G), double or triple 28 bp tandem repeat in 5’-untranslated enhanced region of Thymidylate Synthase (TSER), and 6 bp deletion at nucleotide1494 in TS 3’-untranslated region (TS3’UTR). To analyze all genetic polymorphisms simultaneously, we calculated the Genetic Risk Score (GRS). Results: We observed no differences between the Remission and Persistence groups regarding the GRS. Also, there were no differences in the genotypic and allelic distribution of MTHFR C677T and MS A2756G polymorphisms. However, the risk of persistence was higher among women with the heterozygote genotype - ins/del [OR (IC95%): 3.22 (1.19 – 8.69), p=0.021], or the polymorphic genotype – del/del [OR (IC95%): 6.50 (1.71 – 24.70), p=0.006] of TS3’UTR. Conclusions: The presence of the TS3’UTR polymorphism increased the risk of persistence of cervical abnormalities. This genetic variant could be a potential marker of cervical carcinogenesis and therefore assist the follow-up of women with persistent pre-neoplastic cervical lesions.

scholarly journals Genetic polymorphisms in one-carbon metabolism increased the risk of persistence of pre-neoplastic cervical lesions

2019 ◽  
Author(s):  
Nayara Nascimento Toledo Silva ◽  
Ana Carolina Silva Santos ◽  
Verlândia Mendes Nogueira ◽  
Cláudia Martins Carneiro ◽  
Angelica Alves Lima
Keyword(s):  
Genetic Polymorphism ◽  
Carbon Metabolism ◽  
Mthfr C677t ◽  
Methionine Synthase ◽  
Cervical Carcinogenesis ◽  
Cervical Lesions ◽  
Neoplastic Lesion ◽  
One Carbon Metabolism ◽  
Ms A2756g

Abstract Background: Cervical cancer is caused by high-risk Human Papillomavirus (hr-HPV) infection associated with cofactors that has been analyzed as predictors of cytological abnormalities remission or persistence. These cofactors may be classified as environmental, epigenetic or genetic. Polymorphism in genes of enzymes that act on one-carbon metabolism alter their activity and may be associated with cervical carcinogenesis because they affect DNA synthesis and repair, and gene expression. Therefore, the objective of this study was to analyze the risk of persistence of pre-neoplastic cervical lesions according to genetic polymorphisms involved in one-carbon metabolism. Sample group was divided in Remission (n=60) - presence of pre-neoplastic lesion at first meeting (T1), and normal cytology after six months of follow-up (T2), and Persistence (n=46) - presence of pre-neoplastic lesion at T1 and T2. Cervical samples were obtained for cytological analysis (T1 and T2), HPV detection (T1), and evaluation of polymorphism C667T of Methylenetetrahydrofolate Reductase (MTHFR C677T), A2756G of Methionine Synthase (MS A2756G), A66G of Methionine Synthase Reductase (MTRR A66G), double or triple 28 bp tandem repeat in 5'-untranslated enhanced region of Thymidylate Synthase (TSER), and 6 bp deletion at nucleotide1494 in TS 3'-untranslated region (TS3'UTR). Genetic Risk Score (GRS) was calculated for analyze all genetic polymorphism simultaneously. Results: No differences were observed between Remission and Persistence groups of GRS, or genotypic and allelic distribution of MTHFR C677T and MS A2756G polymorphisms. However, higher risk of persistence was observed among women presenting heterozygote genotype - ins/del [OR (IC95%): 3.22 (1.19 – 8.69), p=0.021], or polymorphic genotype – del/del [OR (IC95%): 6.50 (1.71 – 24.70), p=0.006] of TS3’UTR. Conclusions: Presence of TS3’UTR polymorphism increased risk of persistence of cervical abnormalities. This genetic variant could be considered as potential marker of cervical carcinogenesis, assisting follow-up of women with persistent pre-neoplastic cervical lesions.

scholarly journals Non-fasting reference intervals for the Abbott IMxTM homocysteine and AxSYMTM plasma folate assays: influence of the methylenetetrahydrofolate reductase 677 C→T mutation on homocysteine

2000 ◽  
Vol 37 (3) ◽  
pp. 390-398 ◽  
Author(s):  
James G Donnelly ◽  
Phillip A Isotalo
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Mthfr C677t ◽  
Hospital Staff ◽  
Reference Intervals ◽  
Mean Value ◽  
Plasma Homocysteine ◽  
Healthy Individuals ◽  
Plasma Folate ◽  
The Mean ◽  
677T Allele

Plasma homocysteine comes under both genetic and nutritional control. B vitamins and particularly folate are important factors in homocysteine metabolism. We have obtained reference intervals for total plasma homocysteine and plasma folate. We have also determined the influence of methylenetetrahydrofolate reductase (MTHFR) genotype on plasma homocysteine concentrations in healthy individuals. Reference intervals for Abbott IMxTM homocysteine and AxSYMTM plasma folate assays were established using 116 volunteers recruited from hospital staff. Exclusion criteria included cardiac, hepatic or renal disorders, and use of over-the-counter prescription medications. An exception was the inclusion of three women using oral contraceptives and one woman receiving post-menopausal oestrogen supplementation. Methylenetetrahydrofolate reductase 677C-T genotyping was performed on 101 of the volunteers to determine whether the MTHFR 677T allele influences homocysteine concentrations in healthy individuals. Reference intervals for homocysteine and folate were determined using the mean±2 standard deviations of the data. Folate/homocysteine ratios were sorted by MTHFR C677T genotype. Homocysteine correlated negatively with plasma folate. Mean male homocysteine concentrations were significantly higher (9· μmol/L; P<0·05) than the mean value (7·1 μmol/L) obtained for females. Mean homocysteine values were significantly higher in subjects who were homozygous for the MTHFR 677T allele when compared with the 677CC genotype ( P<0·05). Ratios of folate/homocysteine were 20% and 7·44% lower in the male and female 677TT group than in the 677CC group, respectively. The mean homocysteine value of 43 volunteers who were taking multivitamins was not significantly different from that of 73 who were not vitamin supplemented. Conversely, the mean folate value was slightly greater, and statistically significant, in the group taking vitamin supplements. The mean folate values and reference intervals were not significantly different when grouped by sex or age. MTHFR 677C T mutations influenced homocysteine values observed in our study of healthy volunteers, even though we did not observe outright folate-deficient individuals. Our random homocysteine values were similar to the fasting homocysteine values obtained in other studies.

677TT Genotype Is Associated with Elevated Risk of Methotrexate (MTX) Toxicity in Juvenile Idiopathic Arthritis: Treatment Outcome, Erythrocyte Concentrations of MTX and Folates, and MTHFR Polymorphisms

2010 ◽  
Vol 37 (10) ◽  
pp. 2180-2186 ◽  
Author(s):  
JANA TUKOVÁ ◽  
JAROSLAV CHLÁDEK ◽  
MILOS HROCH ◽  
DANA NĚMCOVÁ ◽  
JOZEF HOZA ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Juvenile Idiopathic Arthritis ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr C677t ◽  
Elevated Risk ◽  
Mthfr Polymorphisms ◽  
American College Of Rheumatology ◽  
Genotype Frequencies ◽  
Erythrocyte Concentration ◽  
677T Allele

Objective.To investigate whether methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and erythrocyte concentration of methotrexate (EMTX) could serve as predictors of methotrexate (MTX) efficacy and toxicity in patients with juvenile idiopathic arthritis (JIA).Methods.Genetic analyses and EMTX and folate assessment were performed in 69 patients with JIA aged 2.5–19.6 years (30 male) treated with MTX using a dose-escalation protocol and classified as full responders (disease inactivity; n = 51) or nonresponders (< 30% improvement in pediatric American College of Rheumatology-30 criteria while receiving ≥ 15 mg/m2/week parenteral MTX for at least 3 months; n = 18).Results.Nonresponders were treated with the higher median MTX dose (17.2 vs 12.6 mg/m2/week; p < 0.0001) and accumulated more EMTX (217 vs 106 nmol/l; p < 0.02) and erythrocyte folates (763 vs 592 nmol/l; p = 0.052) than responders. Analysis of MTHFR allele and genotype frequencies in relation to response failed to detect association. The frequency of any adverse effect was 29.4% in responders and 33.3% in nonresponders (p = 0.77). The frequency of 677T allele was elevated in patients with adverse effects (52.4% vs 20.9%; OR 3.88, 95% CI 1.8–8.6, p < 0.002). The probability of any adverse effect was significantly higher in patients with 677TT compared to the 677CC genotype (OR 55.5, 95% CI 2.9–1080, p < 0.001).Conclusion.MTHFR genotyping may have a predictive value for the risk of MTX-associated toxicity in patients with JIA. Despite the lack of therapeutic effect, nonresponders accumulated adequate concentrations of EMTX.

scholarly journals 3’UTR Polymorphism of Thymidylate Synthase gene increased the risk of persistence of pre-neoplastic cervical lesions

2020 ◽  
Author(s):  
Nayara Nascimento Toledo Silva ◽  
Ana Carolina Silva Santos ◽  
Verlândia Mendes Nogueira ◽  
Cláudia Martins Carneiro ◽  
Angelica Alves Lima
Keyword(s):  
Thymidylate Synthase ◽  
Carbon Metabolism ◽  
Mthfr C677t ◽  
Methionine Synthase ◽  
Cervical Carcinogenesis ◽  
Cervical Lesions ◽  
Neoplastic Lesions ◽  
One Carbon Metabolism ◽  
Ms A2756g

Abstract Background: Cervical cancer is caused by high-risk Human Papillomavirus (hr-HPV) infection associated with cofactors that has been analyzed as predictors of the remission or persistence of cytological abnormalities remission or persistence. These cofactors can be either environmental, epigenetic, or genetic. Polymorphism in genes of enzymes that act on one-carbon metabolism alter their activity and also may be associated with cervical carcinogenesis because they affect DNA synthesis and repair, and gene expression. Therefore, this study aimed to analyze the risk of persistence of pre-neoplastic cervical lesions according to genetic polymorphisms involved in one-carbon metabolism. Our sample consisted of 106 women, divided into two groups – Remission (n=60), i.e., with the presence of pre-neoplastic lesions at first meeting (T1) and normal cytology after six months of follow-up (T2), and Persistence (n=46), i.e., with the presence of pre-neoplastic lesions at T1 and T2. We obtained cervical samples for cytological analysis (T1 and T2), HPV detection (T1), and evaluation of polymorphism C667T of Methylenetetrahydrofolate Reductase (MTHFR C677T), A2756G of Methionine Synthase (MS A2756G), A66G of Methionine Synthase Reductase (MTRR A66G), double or triple 28 bp tandem repeat in 5’-untranslated enhanced region of Thymidylate Synthase (TSER), and 6 bp deletion at nucleotide1494 in TS 3’-untranslated region (TS3’UTR). To analyze all genetic polymorphisms simultaneously, we calculated the Genetic Risk Score (GRS). Results: We observed no differences between the Remission and Persistence groups regarding the GRS. Also, there were no differences in the genotypic and allelic distribution of MTHFR C677T and MS A2756G polymorphisms. However, the risk of persistence was higher among women with the heterozygote genotype - ins/del [OR (IC95%): 3.22 (1.19 – 8.69), p=0.021], or the polymorphic genotype – del/del [OR (IC95%): 6.50 (1.71 – 24.70), p=0.006] of TS3’UTR. Conclusions: The presence of the TS3’UTR polymorphism increased the risk of persistence of cervical abnormalities. This genetic variant could be a potential marker of cervical carcinogenesis and therefore assist the follow-up of women with persistent pre-neoplastic cervical lesions.

Metabolic and Genetic Risk Factors for Migraine in Children

Cephalalgia ◽  
2006 ◽  
Vol 26 (6) ◽  
pp. 731-737 ◽  
Author(s):  
F Bottini ◽  
ME Celle ◽  
MG Calevo ◽  
S Amato ◽  
G Minniti ◽  
...  
Keyword(s):  
Genetic Risk ◽  
Methylenetetrahydrofolate Reductase ◽  
Factor V Leiden ◽  
Mthfr C677t ◽  
Factor V ◽  
Mutant Genotype ◽  
Methionine Load ◽  
Increased Risk ◽  
Factor Ii ◽  
Stroke In The Young

Migraine can induce ischaemic stroke, and is considered an independent risk factor for stroke in the young. To date, the nature of the link between migraine and stroke is essentially unknown. Forty-five children were studied. Homocysteine levels (fasting and post methionine load), vitamin B12 and plasma folate levels, factor V Leiden, factor II G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C mutations were examined. Compared with controls, patients with migraine had higher levels of post-methionine load homocysteine values (19.5 ± 4.9 vs. 16.9 ± 1.9; P = 0.025) and significantly lower folate levels (5.8 ± 2.6 vs. 7.5 ± 2.1; P = 0.002). We found a trend toward an increased risk of migraine in subjects carrying a homozygous mutant genotype for MTHFR C677T and MTHFR A1298C polymorphisms. Genetic prothrombotic conditions do not seem to be related to migraine in the young, whereas the biochemical differences between migrainous patients and controls are an appealing topic for further investigation.

scholarly journals No association between common polymorphisms in genes of folate and homocysteine metabolism and the risk of Down's syndrome among French mothers

2005 ◽  
Vol 94 (2) ◽  
pp. 166-169 ◽  
Author(s):  
Abalo Chango ◽  
Nathalie Fillon-Emery ◽  
Clotilde Mircher ◽  
Henri Bléhaut ◽  
Daniel Lambert ◽  
...  
Keyword(s):  
Trisomy 21 ◽  
Methylenetetrahydrofolate Reductase ◽  
Allele Frequencies ◽  
Methionine Synthase ◽  
Reduced Folate Carrier ◽  
French Population ◽  
Maternal Risk ◽  
Methionine Synthase Reductase ◽  
French Case ◽  
Combined Genotypes

The cause of the non-disjunction leading to trisomy 21 remains unclear. Recent evidence has suggested that 5, 10-methylenetetrahydrofolate reductase (MTHFR) and/or methionine synthase reductase (MTRR) might contribute to the maternal risk of trisomy 21. The purpose of the present study was to analyse these findings among the French population and to investigate whether common polymorphisms in genes of the folate and homocysteine pathway, including the MTHFR 677C>T, MTHFR 1298A>C, the methionine synthase (MTR) 2756A>G, the cystathionine β-synthase (CBS) 844Ins68 and the reduced folate carrier (RFC-1) 80G>A polymorphisms, contribute to the risk of trisomy 21. The risk was studied by analysing independent and combined genotypes in 119 case mothers and 119 control mothers. The MTHFR 677T, MTHFR 1298C, MTR2756G, MTRR66G, CBSIns68+ and the RFC-1 80G allele frequencies were not significantly different among French case mothers, compared with control mothers. The risk of having a child with trisomy 21 did not appear to be linked to polymorphisms in genes associated with folate and homocysteine metabolism.

scholarly journals Genotype Prevalence and Allele Frequencies of 5,10-Methylenetetrahydrofolate Reductase (MTHFR) C677T and A1298C Polymorphisms in Italian Newborns

2009 ◽  
Vol 40 (12) ◽  
pp. 732-736 ◽  
Author(s):  
Bruno Zappacosta ◽  
Lucio Romano ◽  
Silvia Persichilli ◽  
Luigi A. Cutrone ◽  
Mirella Graziano ◽  
...  
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Mthfr C677t ◽  
Allele Frequencies

scholarly journals Individualized Folic Acid Supplementation based on Polymorphisms of Methylenetetrahydrofolate Reductase (MTHFR) and Methionine Synthase Reductase (MTRR), Compared with Traditional Folic Acid Supplementation, Reduces Gestational Diabetes Mellitus

2022 ◽  
Author(s):  
Xiaoying Yu ◽  
Le Diao ◽  
Baoying Du ◽  
Ying Wang ◽  
Xiaoqin Xv ◽  
...  
Keyword(s):  
Folic Acid ◽  
Gestational Diabetes ◽  
Pregnant Women ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr C677t ◽  
Allele Frequencies ◽  
Control Group ◽  
Case Group ◽  
Methionine Synthase Reductase ◽  
Mtrr A66g

Abstract Backgroud: Folic Acid (FA) may contribute to the development of gestational diabetes mellitus (GDM), but existing studies are inconsistent. We examined the genotype distributions and allele frequencies of methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C and methionine synthase reductase (MTRR) A66G polymorphisms of pregnant women in China, and compared the effects of individualized folate supplementation and traditional FA supplementation on GDM.Methods: The genotype distributions and allele frequencies of MTHFR C677T, A1298C and MTRR A66G polymorphisms in 968 pregnant women (case group) were tested. FA metabolism was ranked at four levels, and then pregnant women of different levels are supplemented with different doses of FA at different periods. The case group was followed up for pregnancy complications and compared with 1,940 pregnant women traditionally supplemented with FA in the same hospital (control group).Results: The allele frequencies of MTHFR C677T were 63.3% (C) and 36.7% (T), those of MTHFR A1298C were 79.3% (A) and 20.7% (C), and those of MTRR A66G were 75.0% (A) and 25.0% (G). Compared with control group, the incidence of GDM in the case group were significantly lower, especially in high-risk pregnant women after FA supplementation.Conclusion: Traditional FA supplementation based on personal habits is controversial, but the use of polymorphisms of genes to clarify the FA metabolism of pregnant women, appropriate, timely and accurate supplementation of FA can effectively reduce gestational diabetes, especially for high-risk pregnant women.

Association of MTRR A66G polymorphism (but not of MTHFR C677T and A1298C, MTR A2756G, TCN C776G) with homocysteine and coronary artery disease in the French population

2005 ◽  
Vol 94 (09) ◽  
pp. 510-515 ◽  
Author(s):  
Yves Juilliére ◽  
Mirande Candito ◽  
Charles E. Adjalla ◽  
Pierre Gibelin ◽  
Bernard Herbeth ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr C677t ◽  
Methionine Synthase ◽  
French Population ◽  
Methionine Synthase Reductase ◽  
Mtrr A66g ◽  
Artery Disease ◽  
The Individual

Summarymethylenetetrahydrofolate reductase polymorphism (MTHFR C677T) is an established determinant of homocysteine plasma level (t-Hcys) while its association with coronary artery disease (CAD) seems to be more limited. In contrast, the association of the substitutions A2756G of methionine synthase (MTR), A66G of methionine synthase reductase (MTRR) and C776G of transcobalamin (TCN) to both t-Hcys and CAD needs to be evaluated further. The objective was to evaluate the association of these polymorphisms with t-Hcys and CAD in a French population. We investigated the individual and combined effects of these polymorphisms and of vitamin B12 and folates with t-Hcys in 530 CAD patients and 248 matched healthy controls. t-Hcys was higher in the CAD group than in controls (11.8 vs 10.4 μM, P<0.0001) and in carriers of MTRR AA and MTHFR 677TT than in those carrying the most frequent allele of both polymorphisms (13.8 vs 11.4 μM, P=0.0102 and 12.5 vs 11.0 mM, P=0.0065 respectively). The frequency of MTRR A allele was higher in CAD patients than in controls (0.48 [95% CI: 0.44-0.52] vs 0.38 [95% CI: 0.32-0.44], P=0.0081) while no difference was observed for MTHFR 677T frequency. In multivariate analysis, t-Hcys > median and MTRR AA genotype were two significant independent predictors of CAD with respective odds ratios of 3.1 (95 % CI: 1.8-5.1, P<0.0001) and 4.5 (95% CI: 1.5-13.1, P=0.0051). In conclusion, in contrast to North Europe studies, MTRR AA genotype is a genetic determinant of moderate hyperhomocysteinemia associated with CAD in a French population without vitamin fortification.

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