Effects of Methionine Synthase (MS) A2756G and Methionine Synthase Reductase (MSR) A66G Polymorphisms on Methionine Metabolism in Brazilian Pregnant Women and Their Neonates.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3686-3686
Author(s):  
Patricia R. Barbosa ◽  
Sally P. Stabler ◽  
Mario H. Hirata ◽  
Rosario D.C. Hirata ◽  
Robert H. Allen ◽  
...  

Abstract Methionine synthase (MS) is a cobalamin dependent enzyme that catalyses the remethylation of homocysteine to methionine. The methionine synthase reductase (MSR) maintains adequate levels of methylcob(III)alamin, the activated cofactor for MS. The aim of this study was to investigate the effect of MS A2756G and MSR A66G polymorphisms on total homocysteine (tHcy), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) levels in 390 pregnant women and their 292 newborns, from Sorocaba city, Brazil. Genotypes of two polymorphisms were determined by PCR-RFLP. Pregnant women with MS 2756AA genotype have higher tHcy and lower Cbl levels than those with 2756G alleles. The MMA values were increased in neonates with MS 2756AA genotypes (Table 1). There are no difference between the maternal values of Cbl, serum folate, tHcy, MMA and SAM according to MSR A66G genotypes.The values of SAM were lower in neonates with MSR 66G alleles than those with AA genotypes (Table 2). We conclude that MS 2756AA genotypes are associated with higher tHcy levels in pregnant women and higher MMA levels in neonates. The MSR 66GG genotypes is associated with lower SAM levels in neonates. Table 1- Distribution of geometric means and confidence intervals 95% (CI 95%) and numbers of subjects for maternal and neonatal values of cobalamin (Cbl), serum folate, total homocysteine (tHcy), methymalonic acid (MMA) and S- adenosylmethionine (SAM) according to genotypes for the polymorphism MS A2756G. Variables Genotypes for MS A2756G Student t Test AA AG + GG Pregnant Women Cbl (pmol/L) 139 (133 – 144) 235 156 (146 – 166) 129 P= 0.001 SF (nmol/L) 14.3 (13.6 – 15.0) 234 14.5 (13.6 – 15.5) 129 P= 0.667 tHcy( μmol/L) 6.8 (6.5 – 7.1) 235 6.2 (5.9 – 6.6) 128 P= 0.036 MMA(nmol/L) 234 (219 – 245) 194 241 (219 – 265) 106 P= 0.610 SAM(nmol/L) 81.8 (77.9 – 86,0) 229 83.1 (79.1 – 87.4) 124 P= 0.663 Neonates Cbl (pmol/L) 227 (212 – 244) 188 234 (213 – 257) 101 P= 0.646 SF (nmol/L) 32.0 (31.0 – 33.0) 186 32.0 (30.8 – 33.2) 99 P= 0.967 tHcy μmol/L) 5.8 (5.5 – 6.1) 185 5.5 (5.1 – 5.9) 100 P= 0.229 MMA(nmol/L) 383 (364 – 402) 183 342 (317 – 369) 100 P= 0.011 SAM(nmol/L) 188 (181 – 196) 178 182 (168 – 197) 98 P= 0.491 Table 2 - Distribution of geometric means and confidence intervals 95% (CI (%%) and number of subjects for neonatal values of cobalamin (Cbl), serum folate, total homocysteine (tHcy), methylmalonic acid (MMA) and S- adenosylmethionine (SAM) according to genotypes for the polymorphism MSR A66G. Variables Genotypes MSR A66G Student t Test AA AG GG Groups not sharing a common superscript letter are significantly different at P<0.05 based on Tukey’s test Neonates Cbl (pmol/L) 225 (202 – 249) 86 229 (214 – 246) 166 247 (205 – 298) 35 P= 0.602 SF (nmol/L) 33.0 (31.6 – 34.4) 84 31.7 (30.7 – 32.7) 166 31.8 (29.7 – 34.2) 33 P= 0.352 tHcy μmol/L) ( 5.7 (5.3 – 6.2) 84 5.6 (5.3 – 5.9) 165 5.9 (5.3 – 6.6) 34 P= 0.618 MMA (nmol/L) 360 (334 – 389) 84 378 (357 – 400) 163 339 (299 – 384) 34 P= 0.230 SAM (nmol/L) 200 (186 – 215)a 82 184 (176 – 192)a 159 170 (149 – 195)b 33 P= 0.032

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3687-3687
Author(s):  
Elvira M. Guerra-Shinohara ◽  
Patricia R. Barbosa ◽  
Luiz F. Sampaio-Neto ◽  
Rosario D. Hirata ◽  
Mario H. Hirata ◽  
...  

Abstract In the homocysteine metabolic pathway, several key enzymes, including methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR), have been implicated in abnormal homocysteine accumulation in the presence of rare alleles. In previous study, we showed that lower maternal Cbl levels were associated with higher tHcy and lower S-adenosylmethionine/S-adenosylhomocysteine ratio in pregnant women and their neonates.The aim of this study is to investigate whether MTHFR and MTRR polymorphisms are involved in the risk for elevated total homocysteine (tHcy) and its interaction with low cobalamin (Cbl) or serum folate (SF) levels. Genotypes for polymorphisms MTHFR C677T and MTRR A66G were determined by PCR-FLRP. The serum levels of Cbl, SF and tHcy were determined in 377 pregnant women (37–42 weeks of gestational age), and cutoff values for Cbl and SF were considered the first quartile (low values). Four models of univariate logistic regression analyses were used (Table 1). Pregnant women with MTHFR 677T allele have high risk for elevated tHcy that is increased when 677T allele is associated with low Cbl. Increased risk for elevated tHcy is also met when MTRR 66G allele and low Cbl levels were associated. Women with low SF and common MTHFR and MTRR alleles have high risk for elevated tHcy, that is increased when in association with 677T allele or with 66G allele. Interaction between MTHFR C677T and MTRR A66G polymorphisms and vitamins levels in pregnant women Dependent variables Comparation levels (N) P value Odd Ratios 95% CI P for trend: (a) P<0.001; (b) P<0.001; (c) P=0.067; (d) P<0.001 tHcy>8.3μmol/L MTHFR 677CC genotype and Cbl> 115.8 pmol/L (ref) (136) a 1.00 MTHFR 677CC genotype and≤Cbl 115.8 pmol/L (45) 0.298 1.57 0.67 – 3.63 MTHFR 677CT and 677TT genotypes and Cbl>115.8 pmol/L (145) 0.015 2.09 1.16 – 3.77 MTHFR 677CT and 677TT genotypes and≤Cbl 115.8 pmol/L (48) 0.001 4.63 2.22 – 9.65 tHcy>8.3μmol/L MTHFR 677CC genotype and SF > 10.9 nmol/L (ref) (148) b 1.00 MTHFR 677CC genotype and≤SF 10.9 nmol/L (33) 0.008 3.20 1.35 – 7.59 MTHFR 677CT and 677TT genotypes and SF > 10.9 nmol/L (133) 0.035 1.95 1.05 – 3.61 MTHFR 677CT and 677TT genotypes and≤SF 10.9 nmol/L (59) 0.001 6.62 3.31 – 13.26 tHcy>8.3μmol/L MTRR 66AA genotype and Cbl> 115.8 pmol/L (ref) (96) c 1.00 MTRR 66AA genotype and ≤Cbl 115.8 pmol/L (23) 0.222 1.90 0.68 – 5.29 MTRR 66AG and 66GG genotypes and Cbl>115.8 pmol/L (183) 0.418 1.29 0.70 – 2.39 MTRR 66AG and 66GG genotypes and ≤Cbl 115.8 pmol/L (69) 0.013 2.46 1.21 – 5.01 tHcy>8.3μmol/L MTRR 66AA genotype and SF > 10.9 nmol/L (ref) (92) d 1.00 MTRR 66AA genotype and ≤SF 10.9 nmol/L (27) 0.006 3.83 1.47 – 9.96 MTRR 66AG and 66GG genotypes and SF > 10.9 nmol/L (186) 0.399 1.34 0.68 – 2.63 MTRR 66AG and 66GG genotypes and≤SF 10.9 nmol/L (65) 0.001 4.78 2.26 – 10.10 In conclusion, the interaction between MTHFR and MTRR polymorphisms and low folate and cobalamin serum levels may explain the increased risk for elevated tHcy found in pregnant women.


Blood ◽  
2003 ◽  
Vol 101 (7) ◽  
pp. 2483-2488 ◽  
Author(s):  
Leo A. J. Kluijtmans ◽  
Ian S. Young ◽  
Colin A. Boreham ◽  
Liam Murray ◽  
Dorothy McMaster ◽  
...  

A modestly elevated total plasma homocysteine concentration (tHcy) is generally accepted as an independent and graded risk factor for various pathologies, including vascular diseases, neural tube defects, Alzheimer disease, and pregnancy complications. We analyzed 5 common functional polymorphisms in enzymes involved in homocysteine metabolism (ie, methylenetetrahydrofolate reductase [MTHFR] 677C>T and 1298A>C, methionine synthase [MTR] 2756A>G, cystathionine β-synthase [CBS] 844ins68, and methionine synthase reductase [MTRR] 66A>G) in 452 young adults, and quantified their independent and interactive effects on tHcy concentrations. Serum folate, red cell folate, vitamin B12, and tHcy concentrations were significantly influenced by MTHFR 677C>T genotypes. A particularly strong interaction was observed between theMTHFR 677TT genotype and serum folate, which led to a high tHcy phenotype that was more pronounced in males. The genetic contribution to the variance in tHcy was estimated to be approximately 9%, compared with approximately 35% that could be attributed to low folate and vitamin B12. Our study indicates that dietary factors are centrally important in the control of tHcy levels in young adults with additional, but somewhat weaker, genetic effects. These data underscore the potential benefits that may be gained by improving the dietary status of young adults, and provide support for the implementation of folate/B-vitamin food fortification programs.


2019 ◽  
Vol 11 (4) ◽  
pp. 277-284
Author(s):  
Vitrianingsih Vitrianingsih ◽  
Sitti Khadijah

Studi memperkirakan emesis gravidarum terjadi pada 50-90% kehamilan. Mual muntah pada kehamilan memberikan dampak yang signifikan bagi tubuh dimana ibu menjadi lemah, pucat dan cairan tubuh berkurang sehingga darah menjadi kental (hemokonsentrasi). Keadaan ini dapat memperlambat peredaran darah dan berakibat pada kurangnya suplay oksigen serta makanan ke jaringan sehingga dapat membahayakan kesehatan ibu dan janin. Salah satu terapi yang aman dan dapat dilakukan untuk mengurangi keluahan mual muntah pada ibu hamil adalah pemberian aromaterapi lemon. Penelitian bertujuan untuk mengetahui efektifitas aroma terapi lemon untuk menangani emesis gravidarum. Penelitian ini menggunakan rancangan Quasi experiment  dengan  one group pre-post test design. Populasi penelitian adalah ibu hamil yang mengalami emesis gravidarum di Kecamatan Berbah, Sleman. Jumlah sampel 20 ibu hamil trimester pertama yang diambil dengan teknik purposive sampling. Pengukuran mual muntah dilakukan debelum dan setelah  pemberian aromaterapi lemon menggunakan Indeks Rhodes. Analisa data menggunakan uji Paired t-test. Hasil penelitian didapatkan rata-rata skor mual muntah sebelum pemberian aromaterapi lemon berdasarkan Indeks Rhodes pada Ibu Hamil dengan emesis gravidarum yaitu 22,1 dan terjadi penurunan skor setelah pemberian aromaterapi lemon menjadi 19,8. Ada pengaruh pemberian aromaterapi lemon dengan pengurangan mual muntah pada ibu hamil (p-value = 0.017). Berdasarkan hasil penelitian dapat disimpulkan pemberian aromaterapi lemon efektif untuk mengurangi emesis gravidarum pada ibu hamil trimester pertama.  Kata kunci: aromaterapi lemon, emesis gravidarum THE EFFECTIVENESS OF LEMON AROMATHERAPY FOR HANDLING EMESIS GRAVIDARUM   ABSTRACT Studies estimate that nausea and vomiting (emesis gravidarum) occur in 50 – 90% of pregnancies. Nausea and vomiting of pregnancy have a significant impact on the body in which it makes a mother becomes weak, pale, and decreasing body fluid so that the blood becomes thick (hemoconcentration). This situation can slow down blood circulation and inflict the lack of oxygen and food supplies to the body tissues so that it can endanger the health of the mother and fetus. One of the therapies that is safe and can be conducted to reduce nausea and vomiting of pregnancy is by giving the lemon aromatherapy treatment. The research aims to determine the effectiveness of the aroma of lemon therapy to deal with emesis gravidarum. This study applied quasi-experimental research with one group pretest-posttest design. The population of this study was pregnant women who experienced emesis gravidarum. Furthermore, samples were 20 mothers from Berbah, Sleman taken by using a purposive sampling technique. Nausea and vomiting were assessed between before and after giving lemon aromatherapy using the Rhodes Index. The data were analyzed using the paired t-test. The mean score of nausea and vomiting before giving lemon aromatherapy on mother with emesis gravidarum based on the Rhodes Index was 22.1. However, it decreased after given lemon aromatherapy treatment to 19.8. Therefore, there was an effect on giving lemon aromatherapy treatment toward the decrease of nausea and vomiting for pregnant women (p-value = 0.017). Lemon aromatherapy is effective to reduce emesis gravidarum.  Keywords: lemon aromatherapy, emesis gravidarum


2019 ◽  
Author(s):  
Leila Ahmadian ◽  
Reza Khajouei ◽  
Sudabeh Kamali ◽  
Moghaddameh Mirzaee ◽  
Arefeh Ameri

BACKGROUND Today, the Internet may be a promising tool for interventions for pregnant women. However, these kinds of tools are only helpful if users are ready to use them. OBJECTIVE The present study was conducted with the aim of readiness assessment of pregnant women to use the Internet to access health information about pregnancy and childbirth. METHODS This study was carried out on a sample of 384 pregnant women. Data were collected using a valid and reliable questionnaire. The first section of this questionnaire collected demographic characteristics of the participants. The second part of the questionnaire contains 27 questions covering the following components: infrastructure readiness (6 questions); affordability readiness (3 questions); and skill readiness (12 questions). Data were analyzed with SPSS 19.0 using descriptive statistics, Chi-square test, and T-test. RESULTS This study was carried out on a sample of 384 pregnant women. Data were collected using a valid and reliable questionnaire. The first section of this questionnaire collected demographic characteristics of the participants. The second part of the questionnaire contains 27 questions covering the following components: infrastructure readiness (6 questions); affordability readiness (3 questions); and skill readiness (12 questions). Data were analyzed with SPSS 19.0 using descriptive statistics, Chi-square test, and T-test. CONCLUSIONS The use of the Internet by pregnant women depends on factors such as infrastructure, affordability, and skills readiness. This study showed that speed and the quality of the Internet, hardware and software availability, affordability of the Internet, and access to the Internet training were factors in measuring E-health readiness assessment. CLINICALTRIAL Not applicable


Cephalalgia ◽  
2013 ◽  
Vol 33 (7) ◽  
pp. 469-482 ◽  
Author(s):  
Kathryn A Roecklein ◽  
Ann I Scher ◽  
Albert Smith ◽  
Tamara Harris ◽  
Gudny Eiriksdottir ◽  
...  

Aims The C677T variant in the methylenetetrahydrofolate reductase ( MTHFR; EC 1.5.1.20) enzyme, a key player in the folate metabolic pathway, has been associated with increased risk of migraine with aura. Other genes encoding molecular components of this pathway include methionine synthase ( MTR; EC 2.1.1.13) and methionine synthase reductase ( MTRR; EC 2.1.1.135) among others. We performed a haplotype analysis of migraine risk and MTHFR, MTR, and MTRR. Methods Study participants are from a random sub-sample participating in the population-based AGES-Reykjavik Study, including subjects with non-migraine headache ( n = 367), migraine without aura ( n = 85), migraine with aura ( n = 167), and no headache ( n = 1347). Haplotypes spanning each gene were constructed using Haploview. Association testing was performed on single SNP and haplotypes using logistic regression, controlling for demographic and cardiovascular risk factors and correcting for multiple testing. Results Haplotype analysis suggested an association between MTRR haplotypes and reduced risk of migraine with aura. All other associations were not significant after correcting for multiple testing. Conclusions These results suggest that MTRR variants may protect against migraine with aura in an older population.


2006 ◽  
Vol 96 (08) ◽  
pp. 154-159 ◽  
Author(s):  
Rosa-Maria Guéant-Rodriguez ◽  
Guido Anello ◽  
Rosario Spada ◽  
Antonino Romano ◽  
Adrian Fajardo ◽  
...  

SummaryAssociation between methylenetetrahydrofolate reductase polymorphism (MTHFR 677 C>T), a determinant of homocysteine plasma level (t-Hcys), with ischaemc cerebrovascular disease (iCVD) seems to be neutral in North Europe and North America. The association of 2756 A>G of methionine synthase (MTR), 66 A>G of methionine synthase reductase (MTRR) and 776 C>G of transcobalamin (TCN2) needs to be evaluated further. It was the objective of this study to evaluate the association of these polymorphisms, t-Hcys, vitamin B12 and folate levels with iCVD, in an Italian population from Sicily. We investigated the association of these polymorphisms, t-Hcys, vitamin B12 and folate with iCVD in 252 subjects, including 131 cases and 121 sexand agematched healthy controls. t-Hcys was higher in the iCVD group than in controls [15.3 (11.5–17.9) vs. 11.6 (9.4–14.5) µM; P=0. 0007] and also in subjects withTCN2 776CG genotype, compared to homozygous genotypes [13.5 (9.9± 16.9) vs. 11.7 (9.6 ± 14.4) µM; P=0. 0327]. The folate level in cases and controls was consistent with an adequate dietary intake [12.7 (9.0–15.3) vs. 12.5 (9.6–16.9) nM; P=0. 7203]. In multivariate analysis, t-Hcys was a significant independent predictor of iCVD with an odds ratio of 1.14 (95% C.I. : 1.06–1.24; P=0. 0006). No association was found between MTHFR, MTR, MTRR and TCN2 polymorphisms and iCVD risk. We have found an influence of t-Hcys and a neutral effect of MTHFR, MTR, MTRR and TCN2 on iCVD risk in Sicily. The neutral influence of these polymorphisms may be explained by adequate status in folate and vitamin B12. Other factors underlying the increased t-Hcys need further investigations.


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