# Relationship of VDR and VDBP gene polymorphisms with sepsis susceptibility and prognosis

**Authors:** Chan Lian, Kangtai Ying, Haiyan Shao, Haiting Gu, Wenwei Mao

PMC · DOI: 10.3389/fgene.2025.1590750 · Frontiers in Genetics · 2025-04-25

## TL;DR

This study found that specific gene variations in VDR and VDBP are linked to higher sepsis risk and worse outcomes in patients.

## Contribution

The study identifies specific gene polymorphisms (VDR Fok I and VDBP rs4588) as risk factors for sepsis and its prognosis.

## Key findings

- Higher frequencies of VDR Fok I f allele and VDBP rs4588 A allele are associated with increased sepsis risk.
- Elevated APACHE II and SOFA scores are independent risk factors for poor sepsis prognosis.
- The AA genotype at VDBP rs4588 has moderate diagnostic value for sepsis with 52.7% sensitivity and 63% specificity.

## Abstract

This research focused on the association of vitamin D receptor (VDR) and vitamin D binding protein (VDBP) gene polymorphisms with sepsis susceptibility and prognosis.

110 septic patients were selected as the sepsis group, and another 100 patients with common infections who did not develop sepsis as the control group. 28 days death of patients in the sepsis group were counted. Within 24 h of admission, patients were scored by Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) and Sequential Organ Failure Assessment (SOFA). Serum lactate (Lac), C-reactive protein (CRP), procalcitoninogen (PCT) and vitamin D levels were evaluated. All patient DNAs were extracted. The polymorphisms of VDR and VDBP genes and vitamin D genes Fok Ⅰ (rs2228570) and VDBP rs4588 locus were tested and compared in both groups; and the receiver operating characteristic (ROC) curves were plotted to calculate the area under the area under the curve (AUC) and assess the diagnostic value of each indicator for sepsis. Patients in the sepsis group were categorized into a death group and a survival group, the above indicators were compared in the two groups and the factors affecting the prognosis of sepsis patients were analyzed.

Compared to the control group, the sepsis group exhibited higher APACHE II scores, SOFA scores, serum Lac, CRP, PCT levels, VDR Fok Ⅰ (rs2228570) locus f allele and VDBP rs4588 locus A allele frequencies, and lower vitamin D levels (P < 0.05). The ROC curve analysis showed that the AUC for the diagnosis of sepsis using the AA genotype at the VDBP gene rs4588 locus was 0.579 (95% CI: 0.501–0.656) (sensitivity: 52.70%; specificity: 63.00%, P < 0.05). APACHE II and SOFA scores and serum levels of Lac, CRP, and PCT in the death group were raised and vitamin D levels were diminished than those in the survival group (P < 0.05). Raised APACHE II and SOFA scores were independent risk factors affecting sepsis prognosis.

The f allele at the VDR Fok Ⅰ (rs2228570) locus and the A allele at the VDBP rs4588 locus significantly raise the risk of sepsis in patients.

## Linked entities

- **Genes:** VDR (vitamin D receptor) [NCBI Gene 7421], GC (GC vitamin D binding protein) [NCBI Gene 2638]

## Full-text entities

- **Genes:** GC (GC vitamin D binding protein) [NCBI Gene 2638] {aka DBP, DBP-maf, DBP/GC, GRD3, Gc-MAF, GcMAF}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, ENPEP (glutamyl aminopeptidase) [NCBI Gene 2028] {aka APA, CD249, gp160}, LCT (lactase) [NCBI Gene 3938] {aka LAC, LPH, LPH1}, CALCA (calcitonin related polypeptide alpha) [NCBI Gene 796] {aka CALC1, CGRP, CGRP-I, CGRP-alpha, CGRP1, CT}, VDR (vitamin D receptor) [NCBI Gene 7421] {aka NR1I1, PPP1R163}
- **Diseases:** death (MESH:D003643), inflammatory (MESH:D007249), hypertension (MESH:D006973), infection (MESH:D007239), malignant tumors (MESH:D009369), function (MESH:D003291), autoimmune diseases (MESH:D001327), poisoning (MESH:D011041), CL (MESH:D002971), diabetes (MESH:D003920), Organ Failure (MESH:D009102), neonatal sepsis (MESH:D000071074), septic shock (MESH:D012772), Sepsis (MESH:D018805), trauma (MESH:D014947), systemic lupus erythematosus (MESH:D008180), BPD (MESH:D001997), infertility (MESH:D007246), anterior septal myocardial infarction (MESH:D056988), Polycystic Ovary Syndrome (MESH:D011085), liver injury (MESH:D017093), multidrug-resistant tuberculosis (MESH:D018088), tuberculosis (MESH:D014376), acute kidney injury (MESH:D058186), multiple sclerosis (MESH:D009103), microbial infections (MESH:D015163), septic (MESH:D001170), rheumatoid arthritis (MESH:D001172)
- **Chemicals:** alcohol (MESH:D000438), phosphate (MESH:D010710), 25-hydroxyvitamin D (MESH:C104450), calcium (MESH:D002118), agarose (MESH:D012685), vitamin D (MESH:D014807), lactate (MESH:D019344), 1,25(OH)2D3 (MESH:D002117), 25(OH) vitamin D (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** rs7041, rs4588, rs2228570, G>T, T/T, rs7401, rs7975232, rs2189480, thymine (T) to cytosine (C), rs2107301, rs739837

## Full text

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## Figures

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## References

33 references — full list in the complete paper: https://tomesphere.com/paper/PMC12076934/full.md

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Source: https://tomesphere.com/paper/PMC12076934