Folate-metabolizing gene variants and pregnancy outcome of IVF

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Presentation transcript:

Folate-metabolizing gene variants and pregnancy outcome of IVF M. Laanpere, S. Altmäe, T. Kaart, A. Stavreus-Evers, T.K. Nilsson, A. Salumets Reproductive BioMedicine Online Volume 22, Issue 6, Pages 603-614 (June 2011) DOI: 10.1016/j.rbmo.2011.03.002 Copyright © 2011 Reproductive Healthcare Ltd. Terms and Conditions

Figure 1 Distributions of the CTH 1208 G/T genotype among all female IVF patients, patient subgroups according to clinical pregnancy outcome and number of previous IVF failures and fertile controls. Fisher’s exact test was used to estimate whether the genotypic frequencies differed significantly among the studied groups. P-values of Fisher’s exact test are provided. ∗A generalized linear model revealed that individuals with the CTH 1208 GT genotype have a significantly reduced chance of belonging to the patient group with three or more previous IVF failures rather than the fertile control group, compared with individuals with the TT genotype (odds ratio 3.57, 95% confidence interval 1.27–10.04, P=0.016). NS=not statistically significant. Reproductive BioMedicine Online 2011 22, 603-614DOI: (10.1016/j.rbmo.2011.03.002) Copyright © 2011 Reproductive Healthcare Ltd. Terms and Conditions

Figure 2 Overview of folate-mediated one-carbon metabolism, consisting of two cycles that compete for folate cofactors: DNA biosynthesis (blue) and methylation (green). Homocysteine is catabolized in the trans-sulphuration pathway (pink). Genes tested in this study have been shown as blue ellipses with studied polymorphisms listed next to the gene. Tested biochemical markers (folate, homocysteine and vitamin B12) are shown in green. Dotted lines indicate compound transport into the cell. Dashed line represents biochemical reactions where all steps have not been shown. B12=vitamin B12; BHMT=betaine-homocysteine methyltransferase; CTH=cystathionase; DHF=dihydrofolate; dTMP=deoxythymidine monophosphate; dUMP=deoxyuridine monophosphate; FOLR1=folate receptor α; Hcy=homocysteine; MTHFR=methylenetetrahydrofolate reductase; MTR=methionine synthase; R=methyl acceptor, such as DNA or histones; SAH=S-adenosylhomocysteine; SAM=S-adenosylmethionine; SLC19A1=solute carrier family 19 member 1; THF=tetrahydrofolate; TCN2=transcobalamin II. Reproductive BioMedicine Online 2011 22, 603-614DOI: (10.1016/j.rbmo.2011.03.002) Copyright © 2011 Reproductive Healthcare Ltd. Terms and Conditions

Figure 3 Overview of the MTHFR 677 C/T and CTH 1208 G/T heterozygous genotypes’ association with positive IVF outcome and reproductive success. Reproductive BioMedicine Online 2011 22, 603-614DOI: (10.1016/j.rbmo.2011.03.002) Copyright © 2011 Reproductive Healthcare Ltd. Terms and Conditions