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Effect of Genetic Polymorphisms Related to Folate and Homocysteine Metabolism In the Etiology of Recurrent Miscarriages

Authors: Elvira Maria Guerra-Shinohara; Kelma Cordeiro da Silva Giusti; Nathalia Sierra Monteiro; Robson José Lazaro; Fernanda Midori Seino; Carolina Tosin Bueno; Mário Henrique Burlacchini Carvalho; +3 Authors

Effect of Genetic Polymorphisms Related to Folate and Homocysteine Metabolism In the Etiology of Recurrent Miscarriages

Abstract

Abstract Abstract 5136 Introduction: Folic acid deficiency has been associated with obstetric complications such as preeclampsia, placental abruption and recurrent miscarriages (RM). Folic acid is a methyl group donating in various reactions. Low concentrations of 5,10-methylenetetrahydrofolate, the cofactor of enzyme thymidylate synthase, decrease the synthesis of thymidylate, which results in increased ratio deoxyuridylate monophosphate/deoxytimidylate monophosphate (dUMP/dTMP) and increased incorporation of deoxyuridylate triphosphate (dUTP) to DNA. The removal of dUTP by DNA-glycosylase can cause permanent damage to DNA, which may lead to apoptosis or increase the risk of developing cancer. Polymorphisms in genes of enzymes (MTHFR - methylene tetrahydrofolate reductase, MTR - methionine synthase and MTRR - methionine synthase reductase) and also in the gene of the reduced folate carrier (RFC1) were related to reduced folate and increased total homocysteine concentrations and have been associated as risk factors for RM. Material and Methods: 171 women with a history of three or more recurrent miscarriages and 95 healthy women with no history of abortion and having two or more normal babies were included. Weight and height of women were obtained and the body mass index (BMI) was calculated. The presence of antibodies (ANA and anti-DNA) was evaluated using immunofluorescence kits. The genotypes of the polymorphisms MTHFR c. 677C>T, MTR c. 2756A>G and RFC1 c.80G>A were obtained by PCR-RFLP, while genotyping for polymorphisms MTRR c. 66A>G and MTHFR c. 1298A>C was made by real time PCR. Multivariate logistic regression model (forward conditional) was used to obtain the odds ratio and its 95% confidence intervals of having MR (dependent variable). The independent variables were: quartiles of BMI, age range, positive ANA (titer of 1/40), positive anti-DNA (titre 1/10), genotypes for the MTHFR c. 677C>T, MTHFR c.1298A>C, MTR c. 2756A>G, MTRR c. 66A>G and RFC1 c. 80G>A. Results: No differences between the groups were observed for serum total homocysteine or allele frequencies for MTHFR c. 677C>T, MTHFR c. 1298A>C, MTR c. 2756A>G and RFC1 c.80G>A polymorphisms. In a conditional logistic regression analysis the risk of RM was significantly associated with BMI OR [95% CI] = 1.40 [1.02, 1.93] per quartile increase in BMI), positive anti-DNA OR [95% CI] = 7.24 [0.92, 57.25], positive ANA OR [95% CI] = 2.48 [1.21, 5.08], and AA genotype for MTRR c. 66A>G polymorphism (OR [95% CI] = 2.19 [1.16, 4.12]. Conclusion: The etiology of RM is multifactorial and it is associated with increasing of BMI, presence of autoantibodies and AA genotype for MTRR c. 66A>G polymorphism. Disclosures: No relevant conflicts of interest to declare.

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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