FokI genetic variant in the vitamin D receptor (VDR) and neonatal sepsis: a pilot study.

• Grant number: 24/10365-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2024
• End date: October 31, 2025
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Thelma Suely Okay
• Grantee: Otávio Henrique Miranda de Figueiredo
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Currently, it is known that the functions of vitamin D are not restricted to calciumabsorption by osteoclasts and regulation of bone metabolism, and there isgrowing evidence of its importance in regulating the inflammatory system and theimmune system, both innate and adaptive. The present proposal aims todetermine the frequency of the FokI genetic variant present in the gene thatencodes the vitamin D receptor (VDR). Our hypothesis is that there is a higherfrequency of the FokI SNP in the VDR of sepstic newborns. Two amplificationtechniques, a PCR followed by enzymatic restriction with the FokI enzyme (PCRRFLP) and two Real Time PCRs with SybrGreen and sequence-specific primers(Sequence-Specific Primer -SSP) that were designed to detect the FokI geneticvariant or the wild type (normal) will be developed. In the FokI single nucleotidepolymorphism (SNP), there is an exchange of T for C in the first methionine codon(ATG) of exon 2 on the VDR gene, causing the transcription of the messengerRNA (mRNA) to be displaced, giving rise to two mRNAs. In clinical terms, severalstudies have associated the presence of the FokI SNP in the VDR gene withlower serum concentrations of vitamin D3 (active form) and a higher frequency ofdiseases, such as neoplasms (breast, intestine, among others), diabetes mellitus,cardiovascular diseases and different types of infection. In this proposal, we intend to analyze two groups of newborns (NB), one of them with sepsis,subdivided into sepsis confirmed by blood culture or clinical sepsis, and the othergroup composed of uninfected term adequate to gestation age NBs. To date,there are only two studies on the FokI SNP in the VDR in the context of neonatalsepsis, carried out in India and Egypt, with contradictory results. Considering thatneonatal sepsis remains one of the main causes of preventable neonatal death,it seems opportune to develop this topic. We believe that the identification of theFokI SNP in the VDR could help both in the prevention of neonatal sepsis and inthe clinical management of these cases, for example, by stimulating theinvestigation of vitamin D3 concentrations in carriers of the FokI SNP, withsubsequent vitamin D3 supplementation when necessary.