Heme Oxygenase-1 Promoter Polymorphisms and Risk of Spina Bifida

Overview

Journal Birth Defects Res A Clin Mol Teratol

Publisher Wiley

Date 2015 Jul 16

PMID 26173399

Citations 1

Authors

Kazumichi Fujioka

Wei Yang

Matthew B Wallenstein

Hui Zhao

Ronald J Wong

David K Stevenson

Gary M Shaw

Affiliations

Soon will be listed here.

Abstract

Background: Spina bifida is the most common form of neural tube defects (NTDs). Etiologies of NTDs are multifactorial, and oxidative stress is believed to play a key role in NTD development. Heme oxygenase (HO), the rate-limiting enzyme in heme degradation, has multiple protective properties including mediating antioxidant processes, making it an ideal candidate for study. The inducible HO isoform (HO-1) has two functional genetic polymorphisms: (GT)n dinucleotide repeats and A(-413)T SNP (rs2071746), both of which can affect its promoter activity. However, no study has investigated a possible association between HO-1 genetic polymorphisms and risk of NTDs.

Methods: This case-control study included 152 spina bifida cases (all myelomeningoceles) and 148 non-malformed controls obtained from the California Birth Defects Monitoring Program reflecting births during 1990 to 1999. Genetic polymorphisms were determined by polymerase chain reaction and amplified fragment length polymorphisms/restriction fragment length polymorphisms using genomic DNA extracted from archived newborn blood spots. Genotype and haplotype frequencies of two HO-1 promoter polymorphisms between cases and controls were compared.

Results: For (GT)n dinucleotide repeat lengths and the A(-413)T SNP, no significant differences in allele frequencies or genotypes were found. Linkage disequilibrium was observed between the HO-1 polymorphisms (D': 0.833); however, haplotype analyses did not show increased risk of spina bifida overall or by race/ethnicity.

Conclusion: Although, an association was not found between HO-1 polymorphisms and risk of spina bifida, we speculate that the combined effect of low HO-1 expression and exposures to known environmental oxidative stressors (low folate status or diabetes), may overwhelm antioxidant defenses and increase risk of NTDs and warrants further study.

Citing Articles

The Role of Heme Oxygenase-1 Promoter Polymorphisms in Perinatal Disease.

Nakasone R, Ashina M, Abe S, Tanimura K, Rostenberghe H, Fujioka K Int J Environ Res Public Health. 2021; 18(7).

PMID: 33805292 PMC: 8037596. DOI: 10.3390/ijerph18073520.

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