Gene–Lifestyle Interactions in Renal Dysfunction: Polygenic Risk Modulation via Plant-Based Diets, Coffee Intake, and Bioactive Compound Interactions
Abstract
:1. Introduction
2. Methods
2.1. Participants
2.2. Demographic, Anthropometric, and Biochemical Measurements
2.3. Assessment of Kidney Function
2.4. Usual Food Intake Assessment Using a Semi-Quantitative Food Frequency Questionnaire (SQFFQ)
2.5. Dietary Pattern Classification and Inflammatory Index
2.6. Genotyping and Quality Control
2.7. Selection and Characterization of the Genetic Variants Associated with Renal Dysfunction Risk
2.8. PRS Development and Gene–Lifestyle Interactions
2.9. Molecular Docking Analysis of Missense Mutation with Food Compounds
2.10. Statistical Analysis
3. Results
3.1. Demographic and Lifestyle Characteristics
3.2. Biochemical Parameters Related to Metabolic Syndrome
3.3. Lifestyles and Nutrient Intake
3.4. Polygenic Variants and Their Interaction Related to Renal Dysfunction Risk
3.5. Metabolic Functions Related to Genes Involved in the Hypo-eGFR
3.6. Genetic Variants-Lifestyle Interaction with Hypo-eGFR
3.7. Bioactive Compound Interaction with CPS1 rs1047891 Missense Mutation (Thr1406) and Molecular Docking
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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High-GFR (n = 51,084) | Low-GFR (n = 7617) | Adjusted OR and 95% CI | |
---|---|---|---|
Age (years) 2 | 53.3 ± 0.03 | 56.5 ± 0.08 *** | 2.156 (1.975–2.354) |
Gender (male, N %) | 16,105 (33.6) | 3332 (43.7) +++ | 0.701 (0.649–0.756) |
Education <High school | 7268 (19.6) | 1223 (21.2) | 1 |
High school | 27,133 (73.2) | 4172 (72.2) | 1.130 (0.978–1.306) |
>High school | 2687 (7.24) | 412 (7.09) | 1.194 (0.912–1.562) |
MetS (N, %) 3 | 6998 (13.7) | 2148 (28.2) +++ | 1.991 (1.781–2.225) |
CVD (N, %) 4 | 1890 (3.72) | 799 (10.5) +++ | 1.920 (1.625–2.268) |
BMI (kg/m2) 5 | 23.9 ± 0.03 | 24.3 ± 0.05 *** | 1.374 (1.244–1.518) |
Waist Cir. (cm) 6 | 80.6 ± 0.03 | 81.7 ± 0.18 *** | 1.304 (1.168–1.456) |
Serum glucose (mg/dL) 7 | 95.1 ± 0.09 | 97.6 ± 0.48 ** | 1.853 (1.632–2.105) |
Blood HbA1c (%) 8 | 5.71 ± 0.004 | 5.96 ± 0.026 *** | 1.598 (1.339–1.908) |
Serum HDL (mg/dL) 9 | 53.9 ± 0.06 | 51.1 ± 0.31 *** | 0.662 (0.598–0.733) |
Serum LDL (mg/dL) 10 | 118 ± 0.15 | 120 ± 0.39 *** | 1.277 (1.143–1.427) |
Serum TG (mg/dL) 11 | 124 ± 0.39 | 130 ± 1.00 *** | 1.340 (1.210–1.483) |
SBP (mmHg) 12 | 122 ± 0.07 | 122 ± 0.17 | 1.142 (1.032–1.263) |
DBP (mmHg) 13 | 75.7 ± 0.04 | 75.8 ± 0.11 | 1.103 (0.943–1.289) |
Hypertension (N, %) | 2814 (5.51) | 1150 (15.1) +++ | 2.089 (1.887–2.312) |
Insulin resistance (N, %) | 3918 (7.67) | 975 (12.8)*** | 1.473 (1.271–1.707) |
Serum CRP (mg/dL) 14 | 0.137 ± 0.002 | 0.154 ± 0.005 ** | 1.714 (1.254–2.344) |
Serum creatinine (mg/dL) | 0.79 ± 0.001 | 1.24 ± 0.003 | |
Serum uric acid (mg/dL) 15 | 4.60 ± 0.005 | 5.24 ± 0.01 *** | 4.531 (4.036–5.087) |
Blood urinary nitrogen (mg/dL) 16 | 14.4 ± 0.02 | 18.2 ± 0.05 | 3.247 (2.935–3.591) |
Albumin (mg/dL) 17 | 4.62 ± 0.001 | 4.59 ± 0.006 *** | 0.753 (0.683–0.831) |
AST (U/L) 18 | 23.6 ± 0.11 | 24.7 ± 0.30 *** | 1.189 (0.957–1.477) |
ALT (U/L) 19 | 22.3 ± 0.11 | 23.0 ± 0.29 * | 1.170 (1.010–1.355) |
Total bilirubin 20 | 0.73 ± 0.002 | 0.74 ± 0.005 * | 2.432 (2.306–2.565) |
Urinary protein 21 | 1.09 ± 0.002 | 1.33 ± 0.01 *** | 4.653 (3.919–5.524) |
CHR 1 | SNP 2 | Position | Mi 3 | Ma 4 | OR 5 | SE 6 | Adjusted p-Value 7 | Adjusted p-Value 8 | MAF 9 | p-Value for HWE 10 | Gene Names | Location |
---|---|---|---|---|---|---|---|---|---|---|---|---|
2 | rs1047891 (Thr1406Asn) | 211540507 | A | C | 1.172 | 0.0241 | 4.61 × 10−11 | 2.98 × 10−5 | 0.179 | 0.1156 | CPS1 | Missense |
2 | rs3770636 | 170202833 | G | T | 0.881 | 0.0245 | 2.3 × 10−7 | 0.00692 | 0.200 | 0.0692 | LRP2 | Intron |
4 | rs5020545 | 77414988 | T | C | 1.149 | 0.0247 | 1.83 × 10−8 | 0.00724 | 0.171 | 0.6204 | SHROOM3 | Intron |
5 | rs3812036 | 176813404 | T | C | 1.122 | 0.0227 | 3.97 × 10−7 | 0.0003224 | 0.219 | 0.7723 | SLC34A1 | Intron |
6 | rs4715517 | 54973761 | A | C | 1.283 | 0.0396 | 2.88 × 10−10 | 0.0002845 | 0.054 | 0.3498 | HCRTR2 | 5′-UTR |
6 | rs140652052 | 33547810 | C | A | 1.259 | 0.0464 | 6.95 × 10−7 | 0.009824 | 0.038 | 0.8193 | BAK1 | Intron |
7 | rs139132767 | 116726021 | G | A | 1.579 | 0.0616 | 1.22 × 10−13 | 0.008934 | 0.018 | 0.2941 | ST7 | Intron |
12 | rs141574969 | 111319366 | G | A | 1.142 | 0.0257 | 2.15 × 10−7 | 0.007747 | 0.159 | 0.1384 | CCDC63 | Intron |
15 | rs1031755 | 53951435 | C | A | 0.8967 | 0.0198 | 3.49 × 10−8 | 0.00043 | 0.403 | 0.4817 | WDR72 | Intron |
22 | rs6001939 | 40892794 | T | C | 0.9098 | 0.0213 | 9.21 × 10−7 | 0.001771 | 0.293 | 0.2773 | MRTFA | Intron |
Gene Set | No. Genes | Beta | Beta SD | SE | p-Value |
---|---|---|---|---|---|
GO BP: Protein autoprocessing | 28 | 0.59988 | 0.02312 | 0.15852 | 7.73 × 10−5 |
GO BP: Regulation of receptor recycling | 22 | 0.66108 | 0.02259 | 0.17705 | 9.46 × 10−5 |
Acevedo liver cancer dn | 516 | 0.1403 | 0.02291 | 0.03774 | 0.0001007 |
GO BERT: Core oligodendrocyte differentiation | 40 | 0.48444 | 0.02231 | 0.14096 | 0.0002951 |
GO CC: Neuronal ribonucleoprotein granule | 3 | 1.6359 | 0.02065 | 0.48121 | 0.0003383 |
Biocarta LDL pathway | 6 | 1.2646 | 0.02257 | 0.37738 | 0.0004037 |
Bhat esr1 targets via akt1 up | 273 | 0.17603 | 0.02104 | 0.05297 | 0.0004456 |
GO CC: Proton transporting atp synthase complex catalytic core f1 | 6 | 1.0336 | 0.01845 | 0.31139 | 0.0004519 |
GO BP: Negative regulation of receptor recycling | 5 | 1.0453 | 0.01703 | 0.31814 | 0.0005096 |
GO BP: Negative regulation of myosin light chain phosphatase activity | 5 | 1.4803 | 0.02412 | 0.4553 | 0.0005756 |
PRS 6 | Low-PRS (n = 17,680) | Medium-PRS (n = 26,672) | High-PRS (n = 9476) | PRS Interaction p-Value |
---|---|---|---|---|
Low-ABD 1 High-ABD | 1 1 | 1.247 (1.151–1.351) 1.396 (1.250–1.558) | 1.534 (1.390–1.693) 1.665 (1.452–1.910) | 0.2522 |
Low-PBD 1 High-PBD | 1 1 | 1.371 (1.266–1.484) 1.162 (1.039–1.299) | 1.628 (1.475–1.797) 1.457 (1.275–1.686) | 0.0215 |
Low-WSD 1 High-WSD | 1 1 | 1.305 (1.199–1.420) 1.285 (1.162–1.421) | 1.555 (1.400–1.728) 1.611 (1.424–1.822) | 0.9430 |
Low-RMD 1 High-RMD | 1 1 | 1.331 (1.230–1.440) 1.232 (1.100–1.379) | 1.592 (1.444–1.755) 1.558 (1.354–1.792) | 0.0756 |
Low-Sodium 2 High-Sodium | 1 1 | 1.301 (1.179–1.435) 1.298 (1.191–1.414) | 1.501 (1.328–1.697) 1.649 (1.484–1.833) | 0.8257 |
Low-Alcohol 3 High-Alcohol | 1 1 | 1.226 (1.124–1.336) 1.391 (1.261–1.534) | 1.526 (1.376–1.694) 1.639 (1.445–1.859) | 0.2312 |
Non-smoker Former + Current smokers | 1 1 | 1.284 (1.187–1.388) 1.338 (1.192–1.502) | 1.620 (1.472–1.784) 1.522 (1.318–1.757) | 0.4421 |
Low Exercise Regular Exercise 4 | 1 1 | 1.140 (1.033–1.259) 1.419 (1.304–1.545) | 1.431 (1.267–1.615) 1.709 (1.538–1.898) | 0.0596 |
Low-Coffee 5 High-Coffee | 1 1 | 1.311 (1.220–1.409) 1.248 (1.078–1.445) | 1.655 (1.513–1.809) 1.344 (1.121–1.611) | 0.0092 |
Low-Tea 6 High-Tea | 1 1 | 1.307 (1.212–1.409) 1.272 (1.119–1.446) | 1.609 (1.466–1.765) 1.496 (1.275–1.754) | 0.2290 |
Low-Vitamin D 7 High-Vitamin D | 1 1 | 1.327 (1.169–1.505) 1.280 (1.191–1.376) | 1.574 (1.440–1.721) 1.521 (1.300–1.780) | 0.2066 |
CPS1 rs1047891 | Major | Heterozygote | Minor | |
Low-Vitamin D 7 High-Vitamin D | 1 1 | 1.235 (1.099–1.388) 1.176 (1.099–1.257) | 1.393 (1.190–1.632) 1.124 (0.833–1.517) | 0.0436 |
Food Components | Foods | WT | MT |
---|---|---|---|
Docking Energy, ΔG (kcal mol−1) | |||
Cichoriin | Chicory | −10.1 | −8.6 |
Malvidin 3-alpha-L-galactoside | Blue berry | −10.1 | −8.6 |
Glyceollin II | Soybeans | −10.6 | −8.7 |
Stigmasteryl glucoside | Soybean oil | −10.2 | −8.5 |
alpha-Carotene | Carrot | −10.9 | −8.6 |
(5R,5’R,6S,8′R)-Luteochrome | Sweet potato | −10.2 | −7.3 |
Tuberoside B | Allium tuberosum | −10.6 | −8.7 |
Cycloartanyl ferulate | Rice bran oil | −10.3 | −8.6 |
delta-Carotene | Carrot tomatoes | −10.5 | −7.7 |
19’-Hexanoyloxymytiloxanthin | Mussel | −10.2 | −8 |
(R)-Hispaglabridin A | Licorice | −10.2 | −8.6 |
5,6,7,8-Tetrahydroxy-3’,4’-dimethoxyflavone | Seville orange | −10.6 | −8.7 |
(3S,3’S,all-E)-Zeaxanthin | Shrimp | −10.9 | −8.3 |
(E)-4-(3,7-Dimethyl-2,6-octadienyl)-1,3,5-trihydroxyxanthone | Garcinia livingstonei | −10.1 | −8.5 |
28-Hydroxymangiferonic acid | Mango | −10.5 | −8.5 |
Soyasaponin ag | Soybeans, pulses | −11.3 | −8.2 |
(S)-Nerolidol 3-O-[a-L-Rhamnopyranosyl-(1->4)-a-L-rhamnopyranosyl-(1->2)-[4-(4-hydroxy-3-methoxycinnamoyl)-(E)-a-L-rhamnopyranosyl-(1->6)]-b-D-glucopyranoside] | Eriobotrya japonica | −10.5 | −8.6 |
3alpha-12-Ursene-3,24-diol | Boswellia serrata | −10.6 | −8.5 |
Hovenidulcioside B2 | Hovenia dulcis | −10.5 | −8.6 |
Vitamin D3 | Egg yolk, liver, tuna | −7.6 | −9.9 |
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Liu, M.; Kim, D.-S.; Park, S. Gene–Lifestyle Interactions in Renal Dysfunction: Polygenic Risk Modulation via Plant-Based Diets, Coffee Intake, and Bioactive Compound Interactions. Nutrients 2025, 17, 916. https://doi.org/10.3390/nu17050916
Liu M, Kim D-S, Park S. Gene–Lifestyle Interactions in Renal Dysfunction: Polygenic Risk Modulation via Plant-Based Diets, Coffee Intake, and Bioactive Compound Interactions. Nutrients. 2025; 17(5):916. https://doi.org/10.3390/nu17050916
Chicago/Turabian StyleLiu, Meiling, Da-Sol Kim, and Sunmin Park. 2025. "Gene–Lifestyle Interactions in Renal Dysfunction: Polygenic Risk Modulation via Plant-Based Diets, Coffee Intake, and Bioactive Compound Interactions" Nutrients 17, no. 5: 916. https://doi.org/10.3390/nu17050916
APA StyleLiu, M., Kim, D.-S., & Park, S. (2025). Gene–Lifestyle Interactions in Renal Dysfunction: Polygenic Risk Modulation via Plant-Based Diets, Coffee Intake, and Bioactive Compound Interactions. Nutrients, 17(5), 916. https://doi.org/10.3390/nu17050916