Vitamin D deficiency and vitamin D receptor gene polymorphisms as a risk factor for severe early-onset neonatal sepsis

Abstract

Background It is well known that vitamin D, which is one of the fat-soluble vitamins, is responsible for sustaining normal calcium balance and mineralization of the skeletal system. It is now widely considered as a pleiotropic hormone that modulates and regulates many biological processes of different organs including neural, endocrinal, immune processes, and cardiovascular differentiation of cells and apoptosis. Furthermore, vitamin D has a crucial immune-modulatory effect on innate and adaptive immune responses, endothelial cell function and mucosal barriers. Aim We aimed to study the relation between vitamin D level and vitamin D receptor (VDR) gene polymorphisms and the risk of severe early-onset sepsis (EOS) among a group of Egyptian neonates. Participants and methods We carried out a case–control study on 80 newborns with culture-proven EOS and their mothers. Eighty sex and age harmonized healthy neonates and their mothers were selected as controls. Maternal and neonatal serum (25-hydroxy-vitamin D) levels were analyzed using enzyme-linked immunosorbent assay. Genotyping of both cases and controls for the VDR gene (Fok1, Apa1, Taq1, and Bsm1) polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism. Cases were followed-up to detect the outcome. Results Cases and their mothers had a significant deficient vitamin D level compared with controls (P=0.000). Genotype frequency for all studied VDR gene polymorphisms, was in accordance with Hardy–Weinberg equilibrium among cases and controls, except for Fok1 genotype frequency in cases. VDR Fok1 F/f and f/f genotype and f allele were significantly higher in frequency among neonatal cases than among controls with odd ratio (95% confidence interval), and P value of 9.18 (4.31–19.81); P=0.000, 8.25 (2.36–28.83); P=0.000 and 4.52 (2.65–7.71); P=0.000, respectively. There was a significant association between low vitamin D level and increased Fok1 F/f, f/f genotype and f allele frequency and severity of sepsis and poor outcome. Conclusion Vitamin D deficiency and VDR gene Fok1 polymorphism are associated with increased severity of neonatal EOS.