Heme oxygenase‐1 promoter polymorphisms and risk of spina bifida

Abstract

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.

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

“…Recently, we carried out a case-control study with 300 Californian cohorts to investigate the association between two functional HMOX1 polymorphisms and this entity. In this study, although we observed a doubling in risk for the A allele in A(-413)T among non-Hispanic whites, we did not find an obvious risk association in the whole population [ 17 ].…”

“…Spina bifida is a common congenital disorder characterized by abnormal closure of the embryonic neural tube. Its etiologies are multifactorial, including low maternal folate intake, maternal obesity, and maternal diabetes, each of which is associated with oxidative stress [ 17 ]. Since this etiology is also implicated in a strong genetic contribution, SNPs related to folate production or oxidative stress have been investigated.…”

“…The length of GT repeats is highly polymorphic, ranging from 16 to 45 based on several studies, and is known to have a bimodal distribution with peaks around 23 and 30 repeats in the general Caucasian, Hispanic, and Asian populations [ 15 , 17 , 18 , 19 , 20 ]. In the African population, especially in malaria-endemic areas, there are additional distinct peaks of around (GT) 39 repeats, possibly due to the survival advantage from Plasmodium falciparum infection [ 21 , 22 ].…”

HMOX1 Genetic Polymorphisms Display Ancestral Diversity and May Be Linked to Hypertensive Disorders in Pregnancy

“…HMOX1 genotyping of genomic DNA from patients in PE registry (HDP cohort) was carried out as follows: GTn genotypes were determined using PCR and fragment analyses, modified from a previous study [ 23 ]. Briefly, the GTn region was amplified by PCR using primer pairs with 5′ FAM (fluorescein)-labeled forward primer (F: 5′-6-FAM-AGAGCCTGCAGCTTCTCAGA-3′, R: 5′-ACAAAGTCTGGCCATAGGAC-3′), and the size of the labeled PCR product was determined by fragment analyses using ABI 3130 × Genetic Analyzer and Peakscanner (Thermo Fisher Cloud), with GeneScan-500ROX (Applied Biosystems) as a size marker.…”

“…A/T SNP (rs2071746) of patient samples was genotyped using TaqMan SNP genotyping assay (Cat 4351379, Applied Biosystems), 7900HT Real-Time PCR system, and TaqMan Genotyper software following the manufacturer’s instructions. Haploview 4.1 [ 24 ] was used to perform haplotype analyses, including accessing linkage disequilibrium and haplotype-HDP association analysis, with GTn variant being simplified as a SNP variant [ 23 ].…”