# Development of a Sex-Specific Prevalent Hypertension Discrimination Model in Korean Adults Using Genetic Risk Scores and Clinical Biomarkers: A Cross-Sectional Study

**Authors:** Jua Park, Ximei Huang, Minjoo Kim

PMC · DOI: 10.3390/cimb48030271 · 2026-03-03

## TL;DR

This study developed sex-specific models to predict hypertension in Korean adults by combining genetic risk scores with clinical biomarkers.

## Contribution

The novel contribution is the creation of a sex-specific hypertension discrimination model using genetic and clinical data in a Korean population.

## Key findings

- A female-specific model achieved high accuracy (AUC = 0.913) using BMI, ba-PWV, 8-epi-PGF2α, and genetic risk scores.
- The total-sample model had moderate accuracy (AUC = 0.833) with similar biomarkers and genetic risk scores.
- No stable male-specific genetic risk score model met the study's criteria.

## Abstract

Genetic and metabolic factors contribute to hypertension, yet integrated sex-specific models remain limited. In this cross-sectional study, we developed sex-specific models to discriminate prevalent hypertension discrimination by integrating genetic risk scores (GRSs) with metabolic and vascular biomarkers. From 2075 Korean adults, the final models were evaluated using model-specific complete-case datasets (total n = 775; males n = 382; females n = 397). Blood pressure-related single-nucleotide polymorphisms (SNPs) were screened using genome-wide association analyses (p < 1 × 10−5), and selected variants were used to construct weighted GRSs. Models integrating GRSs with body mass index (BMI), brachial–ankle pulse wave velocity (ba-PWV), and urinary 8-epi-prostaglandin F2α (8-epi-PGF2α) were evaluated by multivariable logistic regression and receiver operating characteristic analysis, with 1000-bootstrap internal validation. Three SNPs formed the total-sample GRS (rs13175330, rs117559502, rs62099117; adjusted odds ratio [OR] = 3.20) and three formed the female GRS (rs13175330, rs6001482, rs62099117; adjusted OR = 2.80); no stable male-specific GRS met prespecified criteria. The final discrimination models achieved an area under the curve of 0.833 in the total sample and 0.913 in females (BMI + ba-PWV + 8-epi-PGF2α + GRS), and 0.758 in males (BMI + ba-PWV + 8-epi-PGF2α). These findings support sex-aware hypertension risk characterization and warrant external and prospective validation.

## Linked entities

- **Chemicals:** 8-epi-prostaglandin F2α (PubChem CID 160)

## Full-text entities

- **Genes:** NPPA (natriuretic peptide A) [NCBI Gene 4878] {aka ANF, ANP, ATFB6, ATRST2, CDD, CDD-ANF}, TOP3B (DNA topoisomerase III beta) [NCBI Gene 8940] {aka TOP3B1}, CLIC4 (CLIC family member 4) [NCBI Gene 25932] {aka CLIC4L, H1, MTCLIC, huH1, p64H1}, SRRM1 (serine and arginine repetitive matrix 1) [NCBI Gene 10250] {aka 160-KD, POP101, SRM160}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, SERPINB2 (serpin family B member 2) [NCBI Gene 5055] {aka HsT1201, PAI, PAI-2, PAI2, PLANH2}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, VPREB1 (V-set pre-B cell surrogate light chain 1) [NCBI Gene 7441] {aka CD179a, IGI, IGVPB, VPREB}, SERPINB7 (serpin family B member 7) [NCBI Gene 8710] {aka MEGSIN, PPKN, TP55}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, PAM (peptidylglycine alpha-amidating monooxygenase) [NCBI Gene 5066] {aka PAL, PAM-1, PHM}
- **Diseases:** adiposity (MESH:D018205), GRS (MESH:D030342), Inflammatory (MESH:D007249), COVID (MESH:D000086382), cardiometabolic diseases (MESH:D024821), Hypertension (MESH:D006973), renal fibrosis (MESH:D005355), malignancy (MESH:D009369), metabolic abnormalities (MESH:D008659), Dimorphism (MESH:D015439), vascular and metabolic dysfunction (MESH:D002561), atherogenic (MESH:D050197), systemic (MESH:D015619), premature death (MESH:D003643), obesity (MESH:D009765), injury to (MESH:D014947), cardiovascular, liver, renal, or pancreatic disease (MESH:D010182), IR (MESH:D007333), dyslipidemia (MESH:D050171)
- **Chemicals:** glucose (MESH:D005947), free fatty acids (MESH:D005230), Cr (MESH:D003404), lipid (MESH:D008055), TGs (MESH:D014280), 8-epi-PGF2alpha (MESH:C075750), MDA (MESH:D008315), cholesterol (MESH:D002784), 8-epi- (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** rs142983199, rs4857055, A>G, (AUC) of 0, rs117559502, rs1915872, rs6001482, rs116861740, rs12539814, rs62099117, rs13175330

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13025723/full.md

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Source: https://tomesphere.com/paper/PMC13025723