Genetic polymorphisms involved in folate metabolism and elevated plasma concentrations of homocysteine: maternal risk factors for Down syndrome in Brazil

Biselli, Joice Matos; Goloni-Bertollo, Eny Maria; Zampieri, Bruna Lancia; Haddad, Renato; Eberlin, Marcos N.; Pavarino, Érika Cristina

doi:10.4238/vol7-1gmr388

Cited by 61 publications

(70 citation statements)

References 43 publications

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“…Several studies have been conducted on the role of folate gene polymorphisms and metabolism in the pathogenesis of DS to provide evidence and new clues (da Silva et al, 2005;Scala et al, 2006;Wang et al, 2008;Biselli et al, 2008b;Coppedè et al, 2006Coppedè et al, , 2009Neagos et al, 2010;Brandalize et al, 2010). The genes investigated as maternal risk factors for DS include methionine synthase, reduced folate carrier 1 and cystathionine-beta-synthase besides MTHFR and MTRR.…”

Section: Discussionmentioning

confidence: 99%

“…Several investigators have reported that individual polymorphism may be insufficient to cause an increased incidence of birth of children with DS, but that a genotype in which two or more polymorphisms in distinct enzymes of the pathways may lead to increased incidence (Acácio et al, 2005;Coppedè et al, 2006;Biselli et al, 2008b). We explored gene-gene interactions and found the first evidence of a positive interaction between the polymorphic variants of the MTHFR, MTHFD and TC genes.…”

Section: Discussionmentioning

confidence: 99%

“…These results provided further evidence for a major role of gene-gene interactions in the assessment of genetic susceptibility to DS. In the last twenty years, few studies have found the MTHFR C677T polymorphism as an independent risk factor for bearing DS children (James et al, 1999;Hobbs et al, 2000;da Silva et al, 2005;Wang et al, 2007bWang et al, , 2008, and most studies conducted in this field have shown a positive view about the cooperation of MTHFR C677T or A1298C polymorphism with other factors including gene polymorphisms and vitamin intake involved in folate and methyl metabolism (O'Leary et al, 2002;da Silva et al, 2005;Acácio et al, 2005;Rai et al, 2006;Biselli et al, 2008b;Meguid et al, 2008;Coppedè et al, 2006Coppedè et al, , 2009Brandalize et al, 2009Brandalize et al, , 2010, where some of them have been in Chinese populations (Wang et al, 2007b(Wang et al, , 2008Liao et al, 2010). It seems that the MTHFR gene mutation acts as a key factor in the assessment of risk to DS.…”

Section: Discussionmentioning

confidence: 99%

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Combined folate gene MTHFD and TC polymorphisms as maternal risk factors for Down syndrome in China

Liao¹,

Zhang²,

Zhou³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. We examined whether polymorphisms in the methylenetetrahydrofolate dehydrogenase (MTHFD) and transcobalamin (TC) genes, which are involved in folate metabolism, affect maternal risk for Down syndrome. We investigated 76 Down syndrome mothers and 115 control mothers from Bengbu, China. Genomic DNA was isolated from the peripheral lymphocytes. Polymerase chain reaction and restriction fragment length polymorphism were used to examine the polymorphisms of MTHFD G1958A and TC C776G. The frequencies of the polymorphic alleles were 24.3 and 19.1% for MTHFD 1958A, 53.9 and 54.2% for TC 776G, in the case and control groups, respectively. No significant differences were found between two groups in relation to either the allele or the genotype frequency for both polymorphisms. However, when gene-gene interactions between these two polymorphisms together with previous studied C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) 1765©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (1): 1764-1773 (2014) Folate gene polymorphisms and the risk of Down syndrome gene were analyzed, the combined MTHFR 677CT/TT and MTHFD 1958AA/GA genotype was found to be significantly associated with the risk of having a Down syndrome child [odds ratio (OR) = 3.11; 95% confidence interval (95%CI) = 1.07-9.02]. In addition, the combined TC 776CG and MTHFR 677TT genotype increased the risk of having a child with Down syndrome 3.64-fold (OR = 3.64; 95%CI = 1.28-10.31).In conclusion, neither MTHFD G1958A nor TC C776G polymorphisms are an independent risk factor for Down syndrome. However, the combined MTHFD/MTHFR, TC/MTHFR genotypes play a role in the risk of bearing a Down syndrome child in the Chinese population.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Combined folate gene MTHFD and TC polymorphisms as maternal risk factors for Down syndrome in China

Liao¹,

Zhang²,

Zhou³

et al. 2014

Genet. Mol. Res.

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“…7,8 Polymorphisms of genes that encode enzymes involved in folate metabolism have been associated with the etiology of DS. [9][10][11][12] A polymorphism of the reduced folate carrier 1 (RFC1) gene consisting of an adenine-to-guanine substitution at position 80 (A80G) has been associated with altered concentrations of products derived from the folate metabolic pathway. 13,14 This has been indicated as a maternal risk factor for DS, in combination with other polymorphisms involved in this metabolism.…”

Section: Introductionmentioning

confidence: 99%

“…13,14 This has been indicated as a maternal risk factor for DS, in combination with other polymorphisms involved in this metabolism. 9,11 The RFC1 gene encodes the reduced folate carrier 1 protein, which plays a role in folic acid absorption, thereby transporting 5-methyltetrahydrofolate, the metabolically active form of folate, into a variety of cells. 15 Polymorphisms of genes encoding cobalamin-transporting proteins such as transcobalamin 2 (TC2) may interfere with the availability of this vitamin in the organism.…”

Section: Introductionmentioning

confidence: 99%

A80G polymorphism of reduced folate carrier 1 (RFC1) and C776G polymorphism of transcobalamin 2 (TC2) genes in Down's syndrome etiology

et al. 2008

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CONTEXT AND OBJECTIVE:There is evidence that polymorphisms of genes involved in folate metabolism may be associated with higher risk that mothers may bear a Down's syndrome (DS) child. This study therefore had the objective of investigating the A80G polymorphism of the reduced folate carrier 1 (RFC1) gene and the C776G polymorphism of the transcobalamin 2 (TC2) gene as maternal risk factors for DS among Brazilian women. DESIGN AND SETTING:Analytical cross-sectional study with control group, at Faculdade de Medicina de São José do Rio Preto (Famerp). METHODS:Sixty-seven mothers of DS individuals with free trisomy 21, and 113 control mothers, were studied. Molecular analysis of the polymorphisms was performed by means of the polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP), followed by electrophoresis on 2% agarose gel. RESULTS:The frequencies of the polymorphic alleles were 0.51 and 0.52 for RFC1 80G, and 0.34 and 0.34 for TC2 776G, in the case and control groups, respectively. Thus, there were no differences between the groups in relation to either the allele or the genotype frequency, for both polymorphisms (P = 0.696 for RFC1 A80G; P = 0.166 for TC2 C776G; P = 0.268 for combined genotypes). CONCLUSION:There was no evidence of any association between the RFC1 A80G and TC2 C776G polymorphisms and the maternal risk of DS in the sample evaluated.

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Polymorphisms in folate pathway genes are not associated with somatic nondisjunction in turner syndrome

Bispo

Santos

Barros

et al. 2015

American J of Med Genetics Pt A

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Folate metabolism dysfunction can lead to DNA hypomethylation and abnormal chromosomal segregation. Previous investigations of this association have produced controversial results. Here we performed a case-control study in patients with Turner syndrome (TS) to determine the effects of genetic polymorphisms of folate pathway genes as potential risk factors for somatic chromosomal nondisjunction. TS is a useful model for this investigation because patients with TS show a high frequency of chromosome mosaicism. Here we investigated the possible association of polymorphisms of the MTHFR gene with TS risk, which has been previously investigated with controversial results. We also examined the effects of MTR, RFC1, and TYMS gene polymorphisms in TS for the first time. The risk was evaluated according to allelic and genotype (independent and combined) frequencies among 70 patients with TS and 144 age-matched healthy control subjects. Polymorphism genotyping was performed by PCR, PCR-RFLP, and PCR-ASA. The polymorphisms MTHFR 677C>T and 1298A>C, MTR 2756A>G, RFC1 80G>A, and TYMS 2R/3R-alone or in combinations-were not associated with the risk of chromosomal aneuploidy in TS. In conclusion, our present findings did not support a link between impaired folate metabolism and abnormal chromosome segregation leading to somatic nondisjunction in TS patients.

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Genetic polymorphisms involved in folate metabolism and elevated plasma concentrations of homocysteine: maternal risk factors for Down syndrome in Brazil

Cited by 61 publications

References 43 publications

Combined folate gene MTHFD and TC polymorphisms as maternal risk factors for Down syndrome in China

Combined folate gene MTHFD and TC polymorphisms as maternal risk factors for Down syndrome in China

A80G polymorphism of reduced folate carrier 1 (RFC1) and C776G polymorphism of transcobalamin 2 (TC2) genes in Down's syndrome etiology

Polymorphisms in folate pathway genes are not associated with somatic nondisjunction in turner syndrome

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