Hypospadias and Intake of Nutrients Related to One-Carbon Metabolism

California Research Division, March of Dimes Foundation, Oakland, California, USA.
The Journal of urology (Impact Factor: 4.47). 12/2008; 181(1):315-21; discussion 321. DOI: 10.1016/j.juro.2008.09.041
Source: PubMed


We examined whether hypospadias is associated with maternal intake of folic acid containing vitamin/mineral supplements or dietary intake of nutrients related to one-carbon metabolism (folate, choline, vitamins B12 and B6, thiamine, riboflavin, methionine and zinc).
The study included births from October 1997 to December 2003 that were part of the National Birth Defects Prevention Study. Diet was assessed by food frequency questionnaire during maternal telephone interviews. Analyses included 915 cases with second or third degree hypospadias (urethra opened at the penile shaft, scrotum or perineum) and 2,266 male, liveborn, nonmalformed controls. All ORs and 95% CIs were estimated from logistic regression models that included several potential confounders. Nutrient based analyses also included energy intake.
Hypospadias risk was not associated with supplement use (adjusted ORs were 1.2, 95% CI 0.9-1.6 for intake beginning in the month before or the first month of pregnancy and 1.1, 95% CI 0.8-1.4 for intake beginning in the second or third month, relative to no intake). Among women who took supplements reduced hypospadias risk was associated with higher dietary intakes of choline, methionine and vitamin B12. The respective ORs (CIs) for the highest vs lowest quartiles were 0.7 (0.5-1.1), 0.6 (0.4-0.9) and 0.7 (0.5-1.0). Among women who did not take supplements increased risk of hypospadias was associated with higher vitamin B12 intake. The OR (CI) for the highest vs lowest quartile was 3.1 (1.1-9.0).
This study suggests an association of hypospadias with intake of certain nutrients related to one-carbon metabolism.

6 Reads
  • Source
    • "We found an association between increased level of propionylcarnitine and the risk of hypospadias in newborns. The presented results support the hypothesis that there is a link between maternal intake of certain nutrients involved in the metabolism of methyl groups and the risk of hypospadias [5]. Some experimental evidence exists in favor of the ameliorative effects of vitamin B12 on teratogen–induced congenital anomalies in rodents [13, 14]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Of interest is if factors like maternal diet can influence the risk of hypospadias-affected pregnancy. Increased propionylcarnitine (C3) is regarded as a biomarker of vitamin B12 deficiency. The retrospective study was undertaken to determine whether increased propionylcarnitine and low methionine in newborns are associated with hypospadias. 41 newborns with hypospadias and 90 control newborns without congenital anomalies were investigated. Whole blood propionylcarnitine and methionine concentrations were measured using tandem mass spectrometry. The mean concentration of propionylcarnitine was higher in newborns with hypospadias compared with newborns without congenital anomalies (p = 0.026). The mean methionine level in cases was insignificantly lower than in controls. There appears to be an association between decreased vitamin B12, as indexed by an increase of propionylcarnitine, and hypospadias in the investigated group of patients.
    Central European Journal of Urology 11/2013; 66(3):377-80. DOI:10.5173/ceju.2013.03.art36
  • Source
    • "MTHFR and OCM play key roles in physiologic processes by regulating the channeling of onecarbon units between the DNA cycle (nucleotide synthesis) and the methylation cycle (Frankenburg, 2007; Krebs et al., 2009; Laanpere et al., 2010). Dysfunction of the OCM cycle has been linked to neural tube defects (van der Put et al., 2001; Zhang et al., 2008) and autism (Pasca et al., 2009), and may contribute to the pathogenesis of other disorders, including leukemia (de Jonge et al., 2009; Wiemels et al., 2001), dementia (Kim et al., 2008; Kronenberg et al., 2009), colorectal cancer (Kim, 1999; Levine et al., 2010), cardiovascular disease (Smulders and Stehouwer, 2005) and congenital abnormalities (Carmichael et al., 2009; Wani et al., 2008). Given MTHFR's essential role in brain function and neurodevelopment (del Rio Garcia et al., 2009; Ueland et al., 2001), and that family and twin studies have demonstrated considerable shared genetic variance between psychiatric disorders (Cardno et al., 2002; Lichtenstein et al., 2009; McGuffin et al., 2003; Van Snellenberg and de Candia, 2009), it is reasonable to hypothesize that genetic variation in MTHFR may contribute to the shared genetic vulnerability of common psychiatric disorders. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Past analyses examining the relationship between genetic variation in the 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene and psychiatric disorders have provided mixed and largely inconclusive findings. MTHFR is involved in the one-carbon metabolic pathway which is essential for DNA biosynthesis and the epigenetic process of DNA methylation. We conducted a meta-analysis of all published case-control studies investigating associations between two common MTHFR single nucleotide polymorphisms (SNPs), MTHFR C677T (sample size 29,502) and A1298C (sample size 7934), and the major psychiatric disorders (i) schizophrenia (SZ), (ii) bipolar disorder (BPD), and (iii) unipolar depressive disorder (UDD). In order to examine possible shared genetic vulnerability, we also tested for associations between MTHFR and all of these major psychiatric disorders (SZ, BPD and UDD) combined. MTHFR C677T was significantly associated with all of the combined psychiatric disorders (SZ, BPD and UDD); random effects odds ratio (OR)=1.26 for TT versus CC genotype carriers; confidence interval (CI) 1.09-1.46); meta-regression did not suggest moderating effects of psychiatric diagnosis, sex, ethnic group or year of publication. Although MTHFR A1298C was not significantly associated with the combination of major psychiatric disorders, nor with SZ, there was evidence for diagnostic moderation indicating a significant association with BPD (random effects OR=2.03 for AA versus CC genotype carriers, CI: 1.07-3.86). Meta-analysis on UDD was not possible due to the small number of studies available. This study provides evidence for shared genetic vulnerability for SZ, BPD and UDD mediated by MTHFR 677TT genotype, which is in line with epigenetic involvement in the pathophysiology of these psychiatric disorders.
    Brain Behavior and Immunity 12/2010; 25(8):1530-43. DOI:10.1016/j.bbi.2010.12.006 · 5.89 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The authors describe the development and testing of a water-tree retardant (WTR) XLPE (cross-linked polyethylene) insulation grade. The major points included are a description of a hypothesis relevant for the growth of water treeing, verification of the efficiency of the material from laboratory to full-scale compound manufacture, showing that it is possible to process the grade on conventional cable production lines, and finally the short- and long-term electrical properties of these cables. All results obtained from the extended processing trials and long-time electrical aging testing under most-severe conditions verify the expectations that the described WTR-XLPE grade exhibits: drastic suppression of the generation of bow-tie trees and vented trees; significant improvement of electrical breakdown strength after wet aging; and excellent extrudability and crosslinking during cable processing. Thus it is affirmed that through use of the investigated WTR insulation grade it would be possible to further extend the life expectancy and reliability of power cables under severe service conditions
    Properties and Applications of Dielectric Materials, 1988. Proceedings., Second International Conference on Properties and Applications of; 10/1988
Show more