Polymorphisms in placental iodothyronine deiodinase genes are not associated with neural tube defects in pregnant women with high maternal serum homocysteine and low thyroid hormone levels

Abstract Background: This study hypothesized that single nucleotide polymorphisms in placental iodothyronine deiodinase genes could be related to neural tube defects in pregnant women with high maternal serum homocysteine and low thyroid hormone levels. Methods: We performed a case-control study between 2007 and 2009 that included pregnant women from the Lüliang Mountains, Shanxi Province, China. Nine distinct single nucleotide polymorphisms in the iodothyronine deiodinase type 1, type 2, and type 3 genes were analyzed using placental samples obtained from 83 pregnant women with fetuses harboring neural tube defects (cases) and 90 pregnant women with fetuses without neural tube defects (controls). The nine single nucleotide polymorphisms were analyzed using the Cochran–Armitage test and the Chi-squared test (Fisher’s exact test). Results: There were no statistically significant associations between the nine placental single nucleotide polymorphisms and neural tube defects (P>0.05). Additionally, no statistically significant relationships were found between the single nucleotide polymorphisms in placental iodothyronine deiodinase genes and neural tube defects among pregnant women with high maternal serum homocysteine and low thyroid hormone levels. Conclusions: Our result in this study supports our previous report, which showed dysregulation of iodothyronine deiodinase type 3 transcription due to histone modifications of the promotor region in a mouse model of spina bifida. Our result also suggests that other factors such as histone modifications of the genes of deiodinases by a higher level of serum total homocysteine rather than single nucleotide polymorphisms of the genes contribute to neural tube defects in pregnant women with high maternal serum homocysteine and low thyroid hormone levels.