scholarly journals MTHFR Genetic Polymorphism As a Risk Factor in Egyptian Mothers with Down Syndrome Children

2008 ◽  
Vol 24 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Nagwa A. Meguid ◽  
Ahmed A. Dardir ◽  
Mohamed Khass ◽  
Lamia El Hossieny ◽  
Afaf Ezzat ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Odds Ratio ◽  
Methylenetetrahydrofolate Reductase ◽  
Folate Intake ◽  
Maternal Risk ◽  
Genotype Frequencies ◽  
Homozygous Genotype ◽  
Significant Difference ◽  
Genetic Impact ◽  
Normal Offspring

Recent reports linking Down syndrome (DS) to maternal polymorphisms at the methylenetetrahydrofolate reductase (MTHFR) gene locus have generated great interest among investigators in the field. The present study aimed at evaluation ofMTHFR677C/T and 1298A/C polymorphisms in theMTHFRgene as maternal risk factors for DS. Forty two mothers of proven DS outcomes and forty eight control mothers with normal offspring were included. Complete medical and nutritional histories for all mothers were taken with special emphasis on folate intake. Folic acid intake from food or vitamin supplements was significantly low (below the Recommended Daily Allowance) in the group of case mothers compared to control mothers. Frequencies ofMTHFR677T andMTHFR1298C alleles were significantly higher among case mothers (32.1% and 57.1%, respectively) compared to control mothers (18.7% and 32.3%, respectively). Heterozygous and homozygous genotype frequencies ofMTHFRat position 677 (CT and TT) were higher among case mothers than controls (40.5% versus 25% and 11.9% versus 6.2%, respectively) with an odds ratio of 2.34 (95% confidence interval [CI] 0.93–5.89) and 2.75 (95% CI 0.95–12.77), respectively. Interestingly, the homozygous genotype frequency (CC) at position 1298 was significantly higher in case mothers than in controls (33.3% versus 2.1% respectively) with an odds ratio of 31.5 (95% CI 3.51 to 282.33) indicating that this polymorphism may have more genetic impact than 677 polymorphism. Heterozygous genotype (AC) did not show significant difference between the two groups. We here report on the first pilot study of the possible genetic association between DS andMTHFR1298A/C genotypes among Egyptians. Further extended studies are recommended to confirm the present work.

scholarly journals The impact of Folate Pathway Polymorphisms Combined to Nutritional Deficiency As a Maternal Predisposition Factor for Down Syndrome

2008 ◽  
Vol 25 (3) ◽  
pp. 149-157 ◽  
Author(s):  
C. B. Santos-Rebouças ◽  
J. C. Corrêa ◽  
A. Bonomo ◽  
N. Fintelman-Rodrigues ◽  
K. C. V. Moura ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Methylenetetrahydrofolate Reductase ◽  
Genetic Profile ◽  
Negative Effects ◽  
Methionine Synthase Reductase ◽  
Genotype Frequencies ◽  
Folate Pathway ◽  
Increased Risk ◽  
Reductase Gene ◽  
The Impact

Polymorphisms in genes encoding folate metabolizing enzymes have been linked to an increased risk of maternal chromosomal nondisjunction in several populations. With the purpose of evaluating this relationship, we compared the frequencies of 677C>T and 1298A>C polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) and 66A>G in the methionine synthase reductase gene (MTRR) between 103 young mothers of Down syndrome (DS) individuals and 108 control mothers, whose offspring was karyotypically normal, correlating it with an estimative of folate and – related micronutrients levels intake. Maternal and paternal transmission frequencies ofMTHFR677T allele were also examined to access potential parent-of-origin effects. PCR-RFLP for genomic DNA was accomplished and allele/genotype frequencies differences were determined using the x2test, whereas pattern of transmission of theMTHFR677 allele was analyzed by transmission disequilibrium test. None of the polymorphisms seemed to be more frequent in case mothers than in controls, either individually or combined. The estimative of nutritional intake revealed that folate consumption median was inadequate in both groups, whereas methionine and zinc consumption medians were significantly greater in control mothers. It suggests that such interaction between genetic profile and environment could predispose this sub group of women to have a DS child. Additional studies focusing the interaction between nutritional intakes, biochemical data and folate pathway polymorphisms are needed to confirm the present results. The possibility of neutralize the biochemical negative effects of folate-related polymorphisms through oral supplementation could provide new targets for DS prevention.

A polymorphic marker Val109Asp in the omentin gene are associated with abdominal obesity in the Kyrgyz population

2016 ◽  
Vol 62 (3) ◽  
pp. 4-8
Author(s):  
Zhainagul T. Isakova ◽  
Elnura T. Talaibekova ◽  
Diana A. Asambaeva ◽  
Alina S. Kerimkulova ◽  
Olga S. Lunegova ◽  
...  
Keyword(s):  
Abdominal Obesity ◽  
Polymorphic Marker ◽  
Genotype Frequencies ◽  
Homozygous Genotype ◽  
Increased Risk ◽  
Significant Difference ◽  
Pcr Rflp ◽  
And Control ◽  
Male Subjects ◽  
Kyrgyz Population

Aim — in this study, we investigated whether polymorphisms Val109Asp in the omentin gene are associated with abdominal obesity in the Kyrgyz population.Material and methods. We genotyped 297 nonrelated adults Kyrgyz individuals. 127 patients (male — 46, female — 81, average age — 53±7,0) with abdominal obesity (elevated waist circumferences ≥102 cm for male subjects and ≥ 88 cm for female) and 170 non-obese control subjects (male — 107, female — 63, average age 51±9). Val109Asp polymorphisms analysis in the omentin gene were performed by PCR-RFLP method.Results. There were significant differences in genotype distributions of rs2274907 between the obese and control cohorts (p=0.01). Frequencies of Asp109Asp, Val109Asp and Val109Val genotypes among patients with abdominal obesity were 48, 40 and 12%, respectively, that differed from those among controls (Asp109Asp — 53%, Val109Aspl — 43% and Val109Val — 4%); there was significant difference in genotype frequencies between two groups (χ²=6,29; p=0,043). Homozygous genotype Val109Val was more frequent in the obese than non-obese group. The genotype Val109Val of omentin gene is associated with a high risk of developing abdominal obesity in the Kyrgyz population (OR=3,12; 95% CI 1,23—7,90). Homozygous genotype Asp109Asp, reduces the risk of developing abdominal obesity (OR=0,82; 95% CI 0,53—1,30). The allelic variants of the polymorphisms Val109Asp in the omentin gene were not found to be associated with abdominal obesity.Conclusion. There is significant association between Val109Asp polymorphism in omentin gene and abdominal obesity in the Kyrgyz Population. An increased risk of abdominal obesity associated with homozygous genotype — Val109Val in omentin gene.

scholarly journals Homocysteine Levels and C677T Polymorphism of Methylenetetrahydrofolate Reductase in Women with Polycystic Ovary Syndrome

2003 ◽  
Vol 88 (2) ◽  
pp. 673-679 ◽  
Author(s):  
Francesco Orio ◽  
Stefano Palomba ◽  
Sebastiano Di Biase ◽  
Annamaria Colao ◽  
Libuse Tauchmanova ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Young Women ◽  
Methylenetetrahydrofolate Reductase ◽  
Polycystic Ovary ◽  
Folate Intake ◽  
Control Group ◽  
C677t Polymorphism ◽  
Ovary Syndrome ◽  
Mthfr Polymorphism ◽  
Significant Difference

The aim of this study was to investigate the homocysteine (Hcy) levels and the C677T polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR), a crucial factor of the Hcy metabolism in young women with polycystic ovary syndrome (PCOS). Seventy young women with PCOS and another 70 healthy women with low folate intake were enrolled. Cases and controls were matched for age, body mass index, and allele frequency. Hcy, vitamin B12, and folate levels were measured, and a genetic analysis of 5,10-MTHFR at nucleotide 677 was performed in all subjects. No difference in mean Hcy levels was observed between PCOS women in comparison to the control group. Considering the different MTHFR polymorphism, no significant difference was found in serum Hcy levels between subjects with PCOS and controls showing CC (10.4 ± 3.1 vs. 9.7 ± 2.9 μmol/liter ± sd) and CT genotypes (10.9 ± 3.8 vs. 11.0 ± 3.2 μmol/liter ± sd). In subjects with a TT homozygous state, a significant (P < 0.05) difference was observed between PCOS and control women (11.5 ± 3.9 vs. 22.0 ± 7.8 μmol/liter ± sd). In conclusion, our data show that in PCOS women, the serum Hcy levels are normal, and the C677T polymorphism of MTHFR does not influence the Hcy levels like in controls.

scholarly journals Influence of IL10 (rs1800896) Polymorphism and TNF-α, IL-10, IL-17A, and IL-17F Serum Levels in Ankylosing Spondylitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Matheus Braga ◽  
Fernanda Formaggi Lara-Armi ◽  
Janisleya Silva Ferreira Neves ◽  
Marco Antônio Rocha-Loures ◽  
Mariana de Souza Terron-Monich ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Serum Levels ◽  
University Hospital ◽  
Nucleotide Polymorphisms ◽  
Genotype Frequencies ◽  
Asas Criteria ◽  
Tnf Α ◽  
Significant Difference

Ankylosing spondylitis (AS) is a chronic autoimmune inflammatory disease that mainly affects the axial and sacroiliac joints. Single-nucleotide polymorphisms (SNPs) in genes encoding cytokines have been associated with AS, which can interfere with the production of these cytokines and contribute to the development of AS. In order to contribute to a better understanding of the pathology of AS, our objective was to investigate a possible association of the IL10 −1082 A>G SNP (rs1800896) with AS and to evaluate the serum levels of TNF-α, IL-10, IL-17A, and IL-17F in AS patients and controls comparing them with their respective genotypes (TNF rs1800629, IL10 rs1800896, IL17A rs2275913, and IL17F rs763780). Patients and controls were selected from the Maringá University Hospital and the Maringá Rheumatism Clinic, in Paraná State, Southern Brazil, and they were diagnosed by the ASAS Criteria. In total, 149 patients and 169 controls were genotyped for the IL10 −1082 A>G polymorphism using a polymerase chain reaction with sequence specific primers (PCR-SSP); the measurement of TNF-α serum levels was performed through the immunofluorimetric test and IL-10, IL-17A, and IL-17F using an ELISA test. There was a high frequency of the IL10 −1082 G allele in AS patients compared with controls with an odds ratio of 1.83 and 95% confidence interval of 1.32 to 2.54, and a significant difference in the genotype frequencies of the IL10 −1082 A/G+G/G between patients and healthy controls, with an odds ratio of 3.01 and 95% confidence interval of 1.75 to 5.17. In addition, increased serum levels of IL-10 were observed in AS patients: 2.38 (IQR, 0.91) pg/ml compared with controls 1.72 (IQR 0.93) pg/ml (P = 0.01). Our results also showed an association between IL17F rs763780 C/T+T/T genotypes and increased serum levels of IL-17F in patients with AS and also in controls. We can conclude that patients with the A/G and G/G genotypes for −1082 A>G (rs1800896) in the IL10 gene are three times more likely to develop AS, that the serum level of IL-10 was higher in AS patients and that the IL17F rs763780 polymorphism can affect the levels of IL-17F in the serum of patients and controls in the same way.

scholarly journals Maternal Risk for Down Syndrome Is Modulated by Genes Involved in Folate Metabolism

2012 ◽  
Vol 32 (2) ◽  
pp. 73-81 ◽  
Author(s):  
Bruna Lancia Zampieri ◽  
Joice Matos Biselli ◽  
Eny Maria Goloni-Bertollo ◽  
Hélio Vannucchi ◽  
Valdemir Melechco Carvalho ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Methylenetetrahydrofolate Reductase ◽  
Methylmalonic Acid ◽  
Folate Metabolism ◽  
Serum Folate ◽  
Vitamin B ◽  
Maternal Risk ◽  
Solute Carrier ◽  
The Impact ◽  
Homocysteine Methyltransferase

Studies have shown that the maternal risk for Down syndrome (DS) may be modulated by alterations in folate metabolism. The aim of this study was to evaluate the influence of 12 genetic polymorphisms involved in folate metabolism on maternal risk for DS. In addition, we evaluated the impact of these polymorphisms on serum folate and plasma methylmalonic acid (MMA, an indicator of vitamin B12status) concentrations. The polymorphismstranscobalamin II (TCN2)c.776C>G,betaine-homocysteine S-methyltransferase (BHMT)c.742A>G,methylenetetrahydrofolate reductase (NAD(P)H) (MTHFR)c.677 C>T and theMTHFR677C-1298A-1317T haplotype modulate DS risk. The polymorphismsMTHFRc.677C>T and solute carrier family19 (folate transporter), member 1 (SLC19A1)c.80 A>G modulate folate concentrations, whereas the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) c.66A>G polymorphism affects the MMA concentration. These results are consistent with the modulation of the maternal risk for DS by these polymorphisms.

Methylenetetrahydrofolate Reductase Polymorphisms C677T and A1298C as Maternal Risk Factors for Down Syndrome in Jordan

2011 ◽  
Vol 15 (1-2) ◽  
pp. 51-57 ◽  
Author(s):  
May F. Sadiq ◽  
Ekhlas A. Al-Refai ◽  
Amjad Al-Nasser ◽  
Mohammad Khassawneh ◽  
Qasem Al-Batayneh
Keyword(s):  
Risk Factors ◽  
Down Syndrome ◽  
Methylenetetrahydrofolate Reductase ◽  
Maternal Risk Factors ◽  
Maternal Risk

scholarly journals Functional Inference of Methylenetetrahydrofolate Reductase Gene Polymorphisms on Enzyme Stability as a Potential Risk Factor for Down Syndrome in Croatia

2010 ◽  
Vol 28 (5) ◽  
pp. 293-298 ◽  
Author(s):  
Jadranka Vraneković ◽  
Ivana Babić Božović ◽  
Nada Starčević Čizmarević ◽  
Alena Buretić-Tomljanović ◽  
Smiljana Ristić ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Methylenetetrahydrofolate Reductase ◽  
Enzyme Stability ◽  
Genotype Frequencies ◽  
Reductase Gene ◽  
Pcr Rflp ◽  
Functional Inference ◽  
The Stability ◽  
And Function ◽  
Methylenetetrahydrofolate Reductase Gene

Understanding the biochemical structure and function of the methylenetetrahydrofolate reductase gene (MTHFR) provides new evidence in elucidating the risk of having a child with Down syndrome (DS) in association with two commonMTHFRpolymorphisms, C677T and A1298C. The aim of this study was to evaluate the risk for DS according to the presence ofMTHFRC677T and A1298C polymorphisms as well as the stability of the enzyme configuration. This study included mothers from Croatia with a liveborn DS child (n= 102) or DS pregnancy (n= 9) and mothers with a healthy child (n= 141).MTHFRC677T and A1298C polymorphisms were assessed by PCR-RFLP. Allele/genotype frequencies differences were determined using χ2test. Odds ratio and the 95% confidence intervals were calculated to evaluate the effects of different alleles/genotypes. No statistically significant differences were found between the frequencies of allele/genotype or genotype combinations of theMTHFRC677T and A1298C polymorphisms in the case and the control groups. Additionally, the observed frequencies of the stable (677CC/1298AA, 677CC/1298AC, 677CC/1298CC) and unstable (677CT/1298AA, 677CT/1298AC, 677TT/1298AA) enzyme configurations were not significantly different. We found no evidence to support the possibility thatMTHFRpolymorphisms and the stability of the enzyme configurations were associated with risk of having a child with DS in Croatian population.

scholarly journals Investigating the Impact of the Down Syndrome Related Common MTHFR 677C>T Polymorphism in the Danish Population

2009 ◽  
Vol 27 (6) ◽  
pp. 279-285 ◽  
Author(s):  
Haris Kokotas ◽  
Maria Grigoriadou ◽  
Margareta Mikkelsen ◽  
Aglaia Giannoulia-Karantana ◽  
Michael B. Petersen
Keyword(s):  
Down Syndrome ◽  
Methylenetetrahydrofolate Reductase ◽  
Small Sample Size ◽  
Small Sample ◽  
Chromosome 21 ◽  
Danish Population ◽  
Maternal Risk ◽  
The Common ◽  
Or Gene ◽  
The Impact

Chromosomal aneuploidy consists the leading cause of fetal death in our species. Around 50% of spontaneous abortions until 15 weeks of gestational age are chromosomally aneuploid, with trisomies accounting for 50% of the abnormal abortions. Trisomy 21 is the most common chromosome abnormality in liveborns and is usually the result of nondisjunction of chromosome 21 in meiosis in either oogenesis or spermatogenesis. To investigate the relationship between folate metabolism and Down syndrome (DS) in a Danish population, we analyzed the common 677C>T genetic polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene. Our cohort consisted of 181 mothers of children with DS versus 1,084 healthy controls. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to examine theMTHFR677C>T polymorphism. No significant association between the polymorphism and the risk for DS was found. We conclude that the commonMTHFR677C>T polymorphism is not likely to be a maternal risk factor for DS in our cohort and that the difference to previous studies can probably be explained by small sample size or geographic variation in gene polymorphisms involving gene-nutritional or gene-gene or gene-nutritional-environmental factors.

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