BACKGROUND: Involvement of development-related gene polymorphisms in multifactorial/polygenic etiology of stillborn/neonatal deaths due to malformations has been insufficiently tested. Since these genes showed evolutional stability and their mutations are very rare, we can assume that their polymorphic variants may be a risk factor associated with the occurrence of developmental disorders of unknown etiology or can enhance the phenotypic variability of known genetic disorders.

MATERIAL AND METHODS: To determine the association of 3 polymorphisms involved in the regulation of the early embryonic development of different organs, we conducted an association study of their relation to the particular malformation. We selected 140 samples of archived paraffin tissue samples from deceased patients in which fetal/neonatal autopsy examination had shown congenital abnormalities as the most likely cause of death. The polymorphisms of OSR1 rs12329305, rs9936833 near FOXF1, and HOXA1 rs10951154 were genotyped using the TaqMan allelic discrimination assay.

RESULTS: After Bonferroni correction for multiple testing, significant allelic association with stillborn/neonatal deaths was observed for rs12329305 (p=7×10–4). In addition, association analysis for the same polymorphism was shown in the subgroup with isolated anomalies (1.25×10^–5), particularly in the subgroup of cases with kidney and heart anomalies (p=4.18×10^–5, p=5.12×10^–8, respectively).

CONCLUSIONS: The findings of the present study showed, for the first time, the role of the OSR1 rs12329305 polymorphism in the development of congenital malformations in cases of stillborn/neonatal death, particularly in those with congenital kidney and heart developmental defects.

Keywords: Alleles, Congenital Abnormalities - genetics, Forkhead Transcription Factors - genetics, Genetic Predisposition to Disease, Genotyping Techniques, Infant, Newborn, perinatal death, Polymorphism, Single Nucleotide - genetics, Stillbirth - genetics, Transcription Factors - genetics