A Cross-Sectional Exploratory Study of Cardiovascular Risk Biomarkers in Non-Obese Women with and without Polycystic Ovary Syndrome: Association with Vitamin D
Abstract
:1. Introduction
2. Results
2.1. Cardiovascular Risk Protein Levels
2.2. Functional and Pathway Enrichment for Dysregulated Proteins
2.3. Correlation Analyses between 25(OH)D3, 1,25(OH)2D3 and Cardiovascular Risk Proteins
2.4. Protein–Protein Interactions
2.5. Multivariable Regression and Predictive Value of the Variables
3. Discussion
4. Materials and Methods
4.1. Study Design
4.2. Statistics
4.3. Systems Biology Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Control (n = 29) | PCOS (n = 29) | p-Value | |
---|---|---|---|
Age (years) | 32.5 ± 4.1 | 31 ± 6.4 | 0.14 |
BMI (kg/m2) | 24.8 ± 1.1 | 25.9 ± 1.8 | 0.56 |
Fasting glucose (nmol/L) | 4.9 ± 0.4 | 4.7 ± 0.8 | 0.06 |
HbA1C (mmol/mol) | 30.9 ± 6.5 | 31.8 ± 3.0 | 0.9 |
HOMA-IR | 1.8 ± 1.0 | 1.9 ± 1.6 | 0.97 |
SHBG (nmol/L) | 104.2 ± 80.3 | 71.7 ± 62.2 | 0.01 |
Free androgen index (FAI) | 1.3 ± 0.5 | 4.1 ± 2.9 ± 4.08 | 0.0001 |
CRP (mg L−1) | 2.34 ± 2.34 | 2.77 ± 2.57 | 0.43 |
AMH (ng/mL) | 24.3 ± 13.1 | 57.2 ± 14.2 | 0.0001 |
25(OH)D3 (laboratory reference range 20–40 ng/mL) | 23.77 (13.72–33.24) | 21.80 (15.63–30.46) | 0.86 |
1,25(OH)2D3 (laboratory reference range 0.02–0.08 ng/mL) | 0.04 (0.03–0.05) | 0.05 (0.035–0.06) | 0.53 |
Genes | Target Protein |
---|---|
BMP-6 | Bone morphogenetic protein 6 |
SLAF7 | SLAM family member 7 |
ATS13 | A disintegrin and metalloproteinase with thrombospondin motifs 13 |
Angiopoietin-1 | Angiopoietin-1 |
Adrenomedullin | Adrenomedullin |
ATS13 | A disintegrin and metalloproteinase with thrombospondin motifs 13 |
SRCN1 | Proto-oncogene tyrosine-protein kinase Src |
IL-6 | Interleukin-6 |
TRAIL R1 | Tumor necrosis factor receptor superfamily member 10A |
IDUA | Alpha-L-iduronidase |
RANK | Tumor necrosis factor receptor superfamily member 11A |
TRAIL R2 | Tumor necrosis factor receptor superfamily member 10B |
Marapsin | Serine protease 27 |
sTie-2 | Angiopoietin-1 receptor, soluble |
TF | Tissue Factor |
PDGF Rb | Platelet-derived growth factor receptor beta |
IL-27 | Interleukin-27 |
Gro-a (CXCL1) | Growth-regulated alpha protein |
PIGR | Polymeric immunoglobulin receptor |
sRAGE | Advanced glycosylation end product-specific receptor, soluble |
Mn SOD | Superoxide dismutase [Mn], mitochondrial |
HGH | Somatotropin |
FST | Follistatin |
IL-1Ra | Interleukin-1 receptor antagonist protein |
PIGF | Placenta growth factor |
BOC | Brother of CDO |
LEG9 | Galectin-9 |
IL-18 Ra | Interleukin-18 receptor 1 |
FCG2B | Low-affinity immunoglobulin gamma Fc region receptor II-b |
Tpo | Thrombopoietin |
MIP-1a | C-C motif chemokine 3 |
SLAF5 | SLAM family member 5 |
PAPPA | Pappalysin-1 |
Renin | Renin |
TSP2 | Thrombospondin-2 |
Lymphotactin | Lymphotactin |
IL-16 | Interleukin-16 |
TARC | C-C motif chemokine 17 |
MMP-7 | Matrilysin |
Bone proteoglycan II | Decorin |
DKK1 | Dickkopf-related protein 1 |
ART | Agouti-related protein |
HB-EGF | Heparin-binding EGF-like growth factor |
GDF2 | Growth/differentiation factor 2 |
MMP-12 | Macrophage metalloelastase |
ACE2 | Angiotensin-converting enzyme 2 |
PD-L2 | Programmed cell death 1 ligand 2 |
TACI | Tumor necrosis factor receptor superfamily member 13B |
Leptin | Leptin |
sCD4 | T-cell surface glycoprotein CD4 |
IgE | Immunoglobulin E |
FGF23 | Fibroblast growth factor 23 |
BNP-32 | Brain natriuretic peptide 32 |
IL-2 sRa | Interleukin-2 receptor subunit alpha |
CVRPs | logFC | Av Expression | T | p Value |
---|---|---|---|---|
LEG9 | 0.24 | 9.95 | 2.4 | 0.02 |
BOC | 0.50 | 10.33 | 2.4 | 0.02 |
MIP-1a | 0.27 | 8.87 | 2.4 | 0.02 |
IL-18 Ra | 0.36 | 12.98 | 2.3 | 0.03 |
Tpo | 0.29 | 6.92 | 2.2 | 0.03 |
IL-1Ra | 0.39 | 11.93 | 2.2 | 0.03 |
PD-L2 | 0.26 | 11.55 | 2.2 | 0.03 |
FCG2B | 0.45 | 10.64 | 2.1 | 0.04 |
HGH | 0.24 | 7.94 | 2.0 | 0.04 |
GO Terms | Count | p-Value | Benjamini |
---|---|---|---|
Biological Processes—Upregulated genes | |||
GO:0006954—inflammatory response | 4 | 5.2 × 10−4 | 5.5 × 10−2 |
GO:0006955—immune response | 4 | 8.6 × 10−4 | 5.5 × 10−2 |
GO:0032760—positive regulation of TNF production | 3 | 9.0 × 10−4 | 5.5 × 10−2 |
Pathway enrichment—Upregulated genes | |||
KEGG_Pathway term: cytokine–cytokine receptor interaction | 5 | 4.4 × 10−5 | 1.1 × 10−3 |
PCOS | ||
---|---|---|
25(OH)D3 | ||
r | p | |
IDUA | −0.570 | 0.01 |
LEG9 | 0.518 | 0.02 |
Angiopoietin-1 | −0.500 | 0.02 |
DKK1 | −0.458 | 0.04 |
Gro-a (CXCL1) | −0.437 | 0.04 |
CONTROL | ||
25(OH)D3 | ||
r | p | |
MMP7 | 0.41 | 0.03 |
1,25(OH)2D3 | ||
TARC | 0.68 | 0.001 |
PAPPA | −0.48 | 0.03 |
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Nandakumar, M.; Das, P.; Sathyapalan, T.; Butler, A.E.; Atkin, S.L. A Cross-Sectional Exploratory Study of Cardiovascular Risk Biomarkers in Non-Obese Women with and without Polycystic Ovary Syndrome: Association with Vitamin D. Int. J. Mol. Sci. 2024, 25, 6330. https://doi.org/10.3390/ijms25126330
Nandakumar M, Das P, Sathyapalan T, Butler AE, Atkin SL. A Cross-Sectional Exploratory Study of Cardiovascular Risk Biomarkers in Non-Obese Women with and without Polycystic Ovary Syndrome: Association with Vitamin D. International Journal of Molecular Sciences. 2024; 25(12):6330. https://doi.org/10.3390/ijms25126330
Chicago/Turabian StyleNandakumar, Manjula, Priya Das, Thozhukat Sathyapalan, Alexandra E. Butler, and Stephen L. Atkin. 2024. "A Cross-Sectional Exploratory Study of Cardiovascular Risk Biomarkers in Non-Obese Women with and without Polycystic Ovary Syndrome: Association with Vitamin D" International Journal of Molecular Sciences 25, no. 12: 6330. https://doi.org/10.3390/ijms25126330