Variations in folate pathway genes are associated with unexplained female infertility

Altmäe, Signe; Stavréus-Evers, Anneli; Ruiz, Jonatan R.; Laanpere, Margit; Syvänen, Tiina; Yngve, Agneta; Salumets, Andres; Nilsson, Torbjörn

doi:10.1016/j.fertnstert.2009.02.025

Cited by 88 publications

(80 citation statements)

References 46 publications

(59 reference statements)

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“…Considering the SLC19A1 gene encodes the RFC1 protein, it is plausible that polymorphism in SLC19A1 gene may interfere with the folate transporting by means of reduced SLC19A1 protein expression (De Table 2 continued Genotype and allele Marco et al 2003;Relton et al 2003). The effects of SLC19A1 G80A polymorphism on cellular folate intake remain uncertain (Whetstine et al 2001;StanislawskaSachadyn et al 2009); however, the G allele of G80A has been suggested as a risk factor for HHcy (Chango et al 2000;Altmae et al 2010), which is speculated to be associated with defective chorionic villous visualization in women with RPL (Nelen et al 2000). In the study, our findings were consistent with previous ones.…”

Section: Discussionmentioning

confidence: 99%

The association of idiopathic recurrent early pregnancy loss with polymorphisms in folic acid metabolism-related genes

et al. 2014

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The aim of this study was to investigate the association between polymorphisms in folic acid metabolism-related genes and idiopathic recurrent early pregnancy loss (REPL). A prospective case-control study was performed on a cohort of 82 REPL patients and 166 healthy controls. Genotyping of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C was assessed by applying polymerase chain reaction for amplification followed by DNA sequencing, for methionine synthase reductase A66G, solute carrier family 19, member 1 (SLC19A1) G80A and C696T, and genotyping was done by utilizing the Sequenom MassARRAY system. The results revealed a significant association between MTHFR A1298C polymorphism and idiopathic REPL. Haplotype analysis indicated that the MTHFR 677C-MTHFR 1298C allele combination was associated with REPL (P \ 0.001). The MTHFR 677C-MTHFR 1298A and SLC19A1 80G-SLC19A1 696C allele combinations had lower frequencies in patients with REPL, but with P [ 0.05 (P = 0.093 and P = 0.084, respectively).

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Section: Discussionmentioning

confidence: 99%

The association of idiopathic recurrent early pregnancy loss with polymorphisms in folic acid metabolism-related genes

et al. 2014

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“…A significant proportion of women presenting for fertility treatment are known to be polymorphic for genes for at least two key enzymes (i.e. 5,10-methylenetetrahydrofolate reductase (MTHFR) and solute carrier family 19, member 1 (SLC19A1)) involved in folate metabolism (Altmäe et al 2010). Mild hyperhomocysteinaemia is prevalent in subjects polymorphic for a number of enzymes involved in folate/methionine metabolism (Midttun et al 2007), and total homocysteine concentrations, measured in follicular fluid, are sensitive to dietary intakes of folic acid (Boxmeer et al 2008) and are associated with pregnancy outcome in clinical IVF cycles (Haggarty et al 2006, Pacchiarotti et al 2007.…”

Section: Introductionmentioning

confidence: 99%

Endogenous folates and single-carbon metabolism in the ovarian follicle, oocyte and pre-implantation embryo

Kwong¹,

Adamiak²,

Gwynn³

et al. 2010

Reproduction

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Maternal B-vitamin status at conception can affect fertility and the health of offspring. This study details transcript expression for genes encoding key enzymes in the linked methionine/folate cycles in the bovine oocyte, somatic cells of the ovarian follicle and pre-implantation embryo. Transcripts for all 12 enzymes that were studied and for the two folate receptors (FOLR1 and FOLR2) and reduced folate carrier (SLC19A1) were expressed in liver cells, but transcripts for betaine-homocysteine methyltransferase and methionine adenosyl transferase 1A were absent in all ovarian cells, and transcripts for FOLR2 were absent in embryonic cells. Transcripts for glycine methyltransferase were also absent/weak in cumulus and granulosa cells. The absence of these enzymes could have a profound effect on single-carbon metabolism within the ovary and pre-implantation embryo. Immunocytochemical analysis revealed SLC19A1 protein expression on the plasma and basal-lateral membranes of the pre-implantation embryo. The folate antagonist methotrexate (MTX) enters the cell via SLC19A1, and in the current study, MTX inclusion in bovine/ovine culture media at either 1 or 10 mM from the 1-cell stage inhibited embryo development beyond the 8-cell stage. Hypoxanthine and thymidine (100 mM) increased the proportion of embryos that developed to blastocysts, but the cell number was reduced by 20%. The reduced uptake of [ 35 S] methionine into intra-cellular S-adenosylmethionine and S-adenosylhomocysteine pools, together with reduced uptake of glutamate and tryptophan, was consistent with depleted intra-cellular pools of reduced folates. These data provide an insight into the importance of maternal dietary folate/B-vitamin status during the peri-conceptional period.Reproduction (2010) 139 705-715

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“…Although other factors need to be considered, such as omega 3 and vitamin D deficiency (refer to paper by Simpson et al in this issue), environmental and genetic factors [75][76][77][78]. Nevertheless, further research is required to determine if there is a link between vitamin B12 and MS. [83,87,88] Visual impairment that causing double vision, inability to focus on the object, optical motor function dysregulation [89] Visual impairment that causing double vision, inability to focus on the object, optical motor function dysregulation [90][91][92] Cranial nerve damage, including thermoregulation, sensory, audiooptical-gustatory impairments, dysarthria [89] Cranial nerve damage, including thermoregulation, sensory, audiooptical-gustatory impairments, dysarthria [93][94][95][96] Tingling sensations, tremor, numbness of the limbs, involuntary movements [97] Tingling sensations, tremor, numbness of the limbs [98][99][100][101] Muscular pain and spasm [97,102] Muscular pain and spasm [3,84] Smooth muscles malfunction, including swallowing difficulty [103] Smooth muscles malfunction, including swallowing difficulty [104,105] Fatigue, lack of energy and weakness [106] Fatigue, lack of energy and general weakness [107][108][109][110][111] Bladder and sexual incontinence [112,113] Bladder and sexual dysfunctions [114]…”

Section: Vitamin B12 Deficiency and Ms Symptoms: Similarities And Difmentioning

confidence: 99%

Is there a Link between Vitamin B and Multiple Sclerosis?

Nemazannikova

Mikkelsen

Stojanovska

et al. 2018

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Damage to the myelin sheath (demyelination) is one of the main manifestations of multiple sclerosis (MS). Interestingly, both MS and vitamin B deficiency results in severe myelin degeneration that leads to loss in neuronal signal transmission. Deficiency in vitamin B complex vary, although common symptoms include fatigue, increased oxidative stress, inflammation and demyelination. In particular, vitamin B12 (cobalamin) has triggered an increased attention for its role in the methylation process, involvement in myelination and remyelination and reversal of MS symptoms. Here we discuss the role of vitamin B complex (B1, B2, B3, B4, B5, B6, B7, B9, B12) in MS. The anti-inflammatory and re-myelinating attributes of vitamin B complex members are promising, although with limited clinical studies. Hence, there is an urgent need for larger scope studies to determine the role of vitamin B supplementation alone, or in combination with other therapeutic agents, in prevention or reversal of MS and aid in improved quality of life of MS patients.

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Variations in folate pathway genes are associated with unexplained female infertility

Cited by 88 publications

References 46 publications

The association of idiopathic recurrent early pregnancy loss with polymorphisms in folic acid metabolism-related genes

The association of idiopathic recurrent early pregnancy loss with polymorphisms in folic acid metabolism-related genes

Endogenous folates and single-carbon metabolism in the ovarian follicle, oocyte and pre-implantation embryo

Is there a Link between Vitamin B and Multiple Sclerosis?

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