Lower vitamin D levels and VDR FokI variants are associated with susceptibility to sepsis: a hospital-based case-control study

Abstract

Background: Vitamin D deficiency has been associated with increased sepsis incidence and mortality in various populations. Vitamin D exerts its effect through vitamin receptor (VDR), and various single nucleotide polymorphisms have been reported to affects the expression and structure of the VDR. In the present study, we investigated the possible role of vitamin D deficiency and VDR polymorphisms in susceptibility to sepsis.

Methods: 576 sepsis patients and 421 healthy controls were enrolled in the present study. Plasma vitamin D levels in patients and healthy controls were quantified by ELISA. Genetic variants in the VDR (FokI, TaqI, BsmI, and ApaI) were genotyped by TaqMan assay.

Results: Reduced serum Vitamin D level was observed in subjects with sepsis compared to healthy controls (p ≤ 0.0001). Further, subjects with septic shock had diminished 25(OH) vitamin D compared to severe sepsis cases (p ≤ 0.0001). FokI variants and minor alleles were more prevalent in sepsis patients compared to healthy controls (Ff: p ≤ 0.0001, χ² =17.39; ff: p=0.001, χ² =10.79; f: p ≤ 0.0001, χ² =23.51). Furthermore, combined plasma levels of 25(OH) vitamin D and FokI polymorphism revealed a significant role in a predisposition to sepsis and septic shock. However, the prevalence of other VDR polymorphisms (TaqI, BsmI and ApaI) were comparable among different clinical categories.

Conclusions: Low 25(OH) vitamin D levels and FokI mutants are associated with an increased risk of sepsis and septic shock in a Chinese cohort.

Clinical significance

• Lower levels of 25-OH vitamin D are highly prevalent in Sepsis patients.

• Subjects harbouring VDR FokI variants are predisposed to susceptibility to sepsis in the studied cohort.

Keywords:

• Vitamin D
• vitamin D receptor
• gene polymorphism
• septic shock
• Chinese

Acknowledgment

The authors thank all patients and healthy controls enrolled in the present study.

Ethical approval

Ethical clearance was obtained from the Institutional Human Ethical Committee of The First People's Hospital of Yunnan Province, and written informed consent was obtained from each participant.

Disclosure statement

No potential conflict of interest was declared by the authors.

Data availability statement

Data will be available upon request to the corresponding author.

Additional information

Funding

The present study was supported by Key Project of Yunnan Provincial Science and Technology Department - Kunming Medical University Joint Special Program of Applied Basic Research [No: 2019FE001(-175)]