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Polymorphisms in thioredoxin genes are associated with prenatal thyroid hormone status in a cohort of high fish-eating pregnant women

Published online by Cambridge University Press:  24 September 2014

A. J. Yeates ,
T. Love ,
K. Engstrom ,
M. S. Mulhern ,
E. M. McSorley ,
G. Watson ,
G. E. Myers ,
E. van Wijngaarden ,
P. W. Davidson  and
C. Shamlaye
...Show all authors
A. J. Yeates
Affiliation:
Northern Ireland Centre for Food and Health, University of Ulster, Coleraine, BT52 1SA
T. Love
Affiliation:
University of Rochester, School of Medicine and Dentistry, NY, USA
K. Engstrom
Affiliation:
Lund University, Sweden
M. S. Mulhern
Affiliation:
Northern Ireland Centre for Food and Health, University of Ulster, Coleraine, BT52 1SA
E. M. McSorley
Affiliation:
Northern Ireland Centre for Food and Health, University of Ulster, Coleraine, BT52 1SA
G. Watson
Affiliation:
University of Rochester, School of Medicine and Dentistry, NY, USA
G. E. Myers
Affiliation:
University of Rochester, School of Medicine and Dentistry, NY, USA
E. van Wijngaarden
Affiliation:
University of Rochester, School of Medicine and Dentistry, NY, USA
P. W. Davidson
Affiliation:
University of Rochester, School of Medicine and Dentistry, NY, USA
C. Shamlaye
Affiliation:
Ministry of Health, Victoria, Mahé, Republic of Seychelles
J. J. Strain
Affiliation:
Northern Ireland Centre for Food and Health, University of Ulster, Coleraine, BT52 1SA
K. Broberg
Affiliation:
Lund University, Sweden
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Abstract

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Proceedings of the Nutrition Society , Volume 73 , Issue OCE2: Irish Section Meeting, 18–20 June 2014, Changing Dietary Behaviour: Physiology Through to Practice , 2014 , E88
Copyright
Copyright © The Authors 2014 

Iodine and selenium are required for synthesis of the thyroid hormones, thyroxine (T4) and triiodothyronine (T3), which are critical for optimal neurodevelopment( Reference Schomburg and Kohrle 1 ). Maternal T4 has previously been shown to positively correlate with child cognitive development in the Seychelles Child Development Study Nutrition Cohort 1 (SCDS NC1)( Reference Davidson, Strain and Myers 2 ). The selenoproteins thioredoxin (TXN) and thioredoxin reductases (TXNRD 1 and 2) protect the thyroid from oxidative stress during hormone synthesis( Reference Leoni, Kimura and Santisteban 3 ). The aim of the present study was to investigate associations between single nucleotide polymorphisms (SNPs) in thioredoxin genes, TXN and TXNRD, with prenatal status of thyroid hormones in the SCDS NC1.

Blood was collected from pregnant women at enrolment and at 28 weeks gestation, from which serum concentrations of thyroid hormones were previously measured and genotyping performed for selected SNPs following leukocyte DNA extraction (n = 170). Univariate analysis of covariance (ANCOVA) was used to compare associations of each genotype with serum hormone concentrations, whilst adjusting for maternal age, BMI and smoking status. For TXN, homozygote minor and heterozygote alleles were combined.

Values are estimated means and their standard errors (SE). Significant differences in means between each allele compared to the reference genotypes for TXNRD1, 2 and TXN (CC, CC and AA respectively) are shown (*P < 0·05, **P < 0·01) from ANCOVA adjusting for maternal age, BMI and smoking.

Minor allele frequency of TXNRD1, TXNRD2 and TXN were calculated as 37%, 39% and 4% respectively. Variations of each genotype were significantly associated with greater concentrations of thyroid hormones. TXNRD1 heterozygous was associated with T4 at both time-points, with TXNRD2 homozygous being associated with T3 at 28 wks and TXN heterozygous with T4 and T3 at both time-points. Results indicate that genetic variation in TXN genes may influence prenatal thyroid hormone concentrations in this cohort of high-fish eating pregnant women. Further research should confirm these results in a larger cohort and investigate the influence of genetic variation in selenoproteins on neurodevelopment.

This work was supported by grants from the US National Institute of Environmental Health Sciences, the National Institutes of Health and the Government of Seychelles.

References

1. Schomburg, L & Kohrle, J (2008) Mol Nutr Food Res 52, 1235–1246.CrossRefGoogle Scholar
2. Davidson, PW, Strain, JJ, Myers, GJ et al. (2008) Neurotoxicol 29, 767–775.CrossRefGoogle Scholar
3. Leoni, SG, Kimura, ET, Santisteban, P et al. (2011) Molec Endocrinol 25, 1924–1935.CrossRefGoogle Scholar