The Role of Polymorphisms in Vitamin D-Related Genes in Response to Vitamin D Supplementation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Subjects
2.2. Anthropometric Measures
2.3. Genetic Analysis of Polymorphisms Related to Vitamin D
2.4. Data Analysis
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ALT | Alanine Aminotransferase |
AST | Aspartate Aminotransferase |
BMI | Body Mass Index |
BUN | Blood Urea Nitrogen |
HWE | Hardy–Weinberg Equilibrium |
IFC | Integrated Fluidic Circuit |
IRB | Institutional Review Board |
LD | Linkage Disequilibrium |
LSP | Locus-Specific Primer |
PCR | Polymerase Chain Reaction |
SNP | Single-Nucleotide Polymorphism |
STA | Specific Target Amplification |
TFBS | Transcription Factor Binding Site |
PCA | Principal Component Analysis |
QU | Qatar University |
WC | Waist Circumference |
1000G | 1000 Genomes |
References
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Mean | 95% CI | Normal Distribution | |
---|---|---|---|
Age | 21.173 | 20.803–21.542 | 0.0004 |
BMI (kg/m2) | 24.344 | 23.298–25.390 | <0.0001 |
Height (cm) | 159.407 | 158.252–160.563 | 0.7273 |
Phase 1 ALT (U/L) | 9.825 | 8.798–10.852 | <0.0001 |
Phase 1 AST (U/L) | 15.072 | 13.967–16.176 | 0.0015 |
Phase 1 BUN (mg/dl) | 9.821 | 9.195–10.447 | 0.0109 |
Phase 1 Calcium (mg/dl) | 9.171 | 8.882–9.459 | 0.6413 |
Phase 1 Creatinine (mg/dl) | 0.463 | 0.437–0.490 | 0.4344 |
Phase 2 ALT (U/L) | 12.948 | 11.525–14.371 | <0.0001 |
Phase 2 AST (U/L) | 16.344 | 15.118–17.571 | 0.0016 |
Phase 2 BUN (mg/dl) | 12.664 | 11.883–13.446 | 0.1309 |
Phase 2 Calcium (mg/dl) | 11.324 | 10.996–11.652 | 0.0367 |
Phase 2 Creatinine (mg/dl) | 0.674 | 0.639–0.708 | 0.0009 |
Vitamin D Total Phase 1 | 11.014 | 9.989–12.038 | 0.1375 |
Vitamin D Total Phase 2 | 34.332 | 31.430–37.234 | 0.8644 |
Waist Circumference (inch) | 33.083 | 31.093–35.073 | <0.0001 |
Weight (kg) | 62.149 | 59.047–65.251 | <0.0001 |
SNP ID | Gene | Chr. | Allele | African (N = 1322) | East Asian (N = 1008) | European (N = 1006) | South Asian (N = 978) | American (N = 694) | Current Study Cohort (N = 89) | HWE p-Value |
---|---|---|---|---|---|---|---|---|---|---|
rs10783219 | VDR | 12 | Ref (T) | 0.023 | 0.441 | 0.332 | 0.33 | 0.51 | 0.55 | 0.29 |
Alt (A) | 0.977 | 0.559 | 0.668 | 0.67 | 0.49 | 0.45 | ||||
rs7139166 | VDR | 12 | Ref (C) | 0.963 | 0.981 | 0.577 | 0.8 | 0.72 | 0.73 | 0.17 |
Alt (G) | 0.037 | 0.019 | 0.423 | 0.2 | 0.28 | 0.27 | ||||
rs731236 | VDR | 12 | Ref (A) | 0.715 | 0.933 | 0.6 | 0.63 | 0.74 | 0.82 | 0.53 |
Alt (G) | 0.285 | 0.067 | 0.4 | 0.37 | 0.26 | 0.18 | ||||
rs757343 | VDR | 12 | Ref (C) | 0.945 | 0.783 | 0.854 | 0.89 | 0.85 | 0.6 | 0.07 |
Alt (T) | 0.055 | 0.217 | 0.146 | 0.11 | 0.15 | 0.4 | ||||
rs4516035 | VDR | 12 | Ref (T) | 0.963 | 0.981 | 0.578 | 0.8 | 0.72 | 0.6 | 0.05 * |
Alt (C) | 0.037 | 0.019 | 0.422 | 0.2 | 0.28 | 0.4 | ||||
rs10741657 | CYP2R1 | 11 | Ref (A) | 0.219 | 0.319 | 0.381 | 0.36 | 0.28 | 0.382 | 0.37 |
Alt (G) | 0.781 | 0.681 | 0.619 | 0.64 | 0.72 | 0.618 | ||||
rs10766197 | CYP2R1 | 11 | Ref (G) | 0.896 | 0.643 | 0.526 | 0.55 | 0.64 | 0.15 | 0.97 |
Alt (A) | 0.104 | 0.357 | 0.474 | 0.45 | 0.36 | 0.85 | ||||
rs12794714 | CYP2R1 | 11 | Ref (G) | 0.897 | 0.632 | 0.553 | 0.56 | 0.49 | 0.17 | 0.67 |
Alt (A) | 0.103 | 0.368 | 0.447 | 0.44 | 0.51 | 0.83 | ||||
rs1562902 | CYP2R1 | 11 | Ref (C) | 0.477 | 0.379 | 0.441 | 0.43 | 0.33 | 0.74 | 0.25 |
Alt (T) | 0.523 | 0.621 | 0.559 | 0.57 | 0.67 | 0.26 | ||||
rs10500804 | CYP2R1 | 11 | Ref (T) | 0.897 | 0.63 | 0.552 | 0.55 | 0.48 | 0.8 | 0.77 |
Alt (G) | 0.103 | 0.37 | 0.448 | 0.45 | 0.52 | 0.2 | ||||
rs1993116 | CYP2R1 | 11 | Ref (A) | 0.219 | 0.32 | 0.388 | 0.35 | 0.28 | 0.77 | 0.74 |
Alt (G) | 0.781 | 0.68 | 0.612 | 0.65 | 0.72 | 0.23 | ||||
rs7116978 | CYP2R1 | 11 | Ref (T) | 0.329 | 0.32 | 0.344 | 0.34 | 0.28 | 0.46 | 0.37 |
Alt (C) | 0.671 | 0.68 | 0.656 | 0.66 | 0.72 | 0.54 | ||||
rs10877012 | CYP27B1 | 12 | Ref (G) | 0.921 | 0.357 | 0.683 | 0.49 | 0.74 | 0.85 | 0.95 |
Alt (T) | 0.079 | 0.643 | 0.317 | 0.51 | 0.26 | 0.15 | ||||
rs4646536 | CYP27B1 | 12 | Ref (A) | 0.756 | 0.354 | 0.681 | 0.42 | 0.72 | 0.03 | 0.37 |
Alt (G) | 0.244 | 0.646 | 0.319 | 0.58 | 0.28 | 0.97 | ||||
rs703842 | CYP27B1 | 12 | Ref (A) | 0.7 | 0.354 | 0.68 | 0.42 | 0.71 | 0.15 | 0.1 |
Alt (G) | 0.3 | 0.646 | 0.32 | 0.58 | 0.29 | 0.85 | ||||
rs11234027 | DHCR7/NADSYN1 | 11 | Ref (G) | 0.651 | 0.696 | 0.808 | 0.65 | 0.76 | 0 | NA |
Alt (A) | 0.349 | 0.304 | 0.192 | 0.35 | 0.24 | 1 | ||||
rs12785878 | DHCR7/NADSYN1 | 11 | Ref (G) | 0.83 | 0.62 | 0.299 | 0.85 | 0.55 | 0.57 | 0.38 |
Alt (T) | 0.17 | 0.38 | 0.701 | 0.15 | 0.45 | 0.43 | ||||
rs3829251 | DNCR7/NADSYN1 | 11 | Ref (G) | 0.743 | 0.702 | 0.809 | 0.65 | 0.77 | 0.15 | 0.94 |
Alt (A) | 0.257 | 0.298 | 0.191 | 0.35 | 0.23 | 0.85 | ||||
rs1155563 | GC | 4 | Ref (T) | 0.943 | 0.664 | 0.756 | 0.68 | 0.81 | 0.6 | 0.14 |
Alt (C) | 0.057 | 0.336 | 0.244 | 0.32 | 0.19 | 0.4 | ||||
rs12512631 | GC | 4 | Ref (T) | 0.647 | 0.775 | 0.653 | 0.74 | 0.57 | 0.75 | 0.19 |
Alt (C) | 0.353 | 0.225 | 0.347 | 0.26 | 0.43 | 0.25 | ||||
rs16846876 | GC | 4 | Ref (A) | 0.853 | 0.74 | 0.702 | 0.7 | 0.78 | 0.403 | 0.04 * |
Alt (T) | 0.147 | 0.26 | 0.298 | 0.3 | 0.22 | 0.596 | ||||
rs17467825 | GC | 4 | Ref (A) | 0.946 | 0.739 | 0.751 | 0.7 | 0.79 | 0.72 | 0.32 |
Alt (G) | 0.054 | 0.261 | 0.249 | 0.3 | 0.21 | 0.28 | ||||
rs222020 | GC | 4 | Ref (C) | 0.633 | 0.416 | 0.162 | 0.13 | 0.21 | 0.73 | 0.17 |
Alt (T) | 0.367 | 0.584 | 0.838 | 0.87 | 0.79 | 0.27 | ||||
rs2282679 | GC | 4 | Ref (T) | 0.95 | 0.739 | 0.753 | 0.7 | 0.79 | 0.12 | 0.79 |
Alt (G) | 0.05 | 0.261 | 0.247 | 0.3 | 0.21 | 0.88 | ||||
rs2298849 | GC | 4 | Ref (A) | 0.573 | 0.599 | 0.801 | 0.84 | 0.78 | 0.6 | 0.05 * |
Alt (G) | 0.427 | 0.401 | 0.199 | 0.16 | 0.22 | 0.4 | ||||
rs2298850 | GC | 4 | Ref (G) | 0.974 | 0.74 | 0.764 | 0.71 | 0.8 | 0.75 | 0.02 * |
Alt (C) | 0.026 | 0.26 | 0.236 | 0.29 | 0.2 | 0.25 | ||||
rs2882679 | GC | 4 | Ref (C) | NA | NA | NA | NA | NA | 0.74 | 0.99 |
Alt (T) | NA | NA | NA | NA | NA | 0.26 | ||||
rs3755967 | GC | 4 | Ref (C) | 0.946 | 0.739 | 0.752 | 0.7 | 0.79 | 0.19 | 0.38 |
Alt (T) | 0.054 | 0.261 | 0.248 | 0.3 | 0.21 | 0.81 | ||||
rs4588 | GC | 4 | Ref (G) | 0.933 | 0.739 | 0.752 | 0.7 | 0.79 | 0.77 | 0.29 |
Alt (T) | 0.067 | 0.261 | 0.248 | 0.3 | 0.21 | 0.23 | ||||
rs7041 | GC | 4 | Ref (A) | 0.906 | 0.7 | 0.417 | 0.46 | 0.46 | 0.75 | 0.16 |
Alt (C) | 0.094 | 0.3 | 0.583 | 0.54 | 0.54 | 0.25 | ||||
rs17219315 | CYP24A1 | 20 | Ref (A) | 0.997 | 1 | 0.982 | 0.98 | 0.99 | 0.22 | 0.43 |
Alt (G) | 0.003 | 0 | 0.018 | 0.02 | 0.01 | 0.88 | ||||
rs2244719 | CYP24A1 | 20 | Ref (C) | 0.239 | 0.129 | 0.428 | 0.29 | 0.52 | 0.15 | 0.97 |
Alt (T) | 0.761 | 0.871 | 0.572 | 0.71 | 0.48 | 0.85 | ||||
rs229624 | CYP24A1 | 20 | Ref (G) | 0.893 | 0.969 | 0.815 | 0.8 | 0.9 | 0.53 | 0.35 |
Alt (A) | 0.107 | 0.031 | 0.185 | 0.2 | 0.1 | 0.47 | ||||
rs2296241 | CYP24A1 | 20 | Ref (G) | 0.508 | 0.594 | 0.467 | 0.58 | 0.58 | 0.54 | 0.19 |
Alt (A) | 0.492 | 0.406 | 0.533 | 0.42 | 0.42 | 0.46 | ||||
rs2426496 | CYP24A1 | 20 | Ref (T) | 0.432 | 0.357 | 0.324 | 0.35 | 0.24 | 0.74 | 0.99 |
Alt (G) | 0.568 | 0.643 | 0.676 | 0.65 | 0.76 | 0.26 | ||||
rs4809960 | CYP24A1 | 20 | Ref (T) | 0.905 | 0.78 | 0.769 | 0.75 | 0.79 | 0.82 | 0.84 |
Alt (C) | 0.095 | 0.22 | 0.231 | 0.25 | 0.21 | 0.18 | ||||
rs6013897 | CYP24A1 | 20 | Ref (T) | 0.74 | 0.851 | 0.758 | 0.67 | 0.63 | 0.72 | 0.37 |
Alt (A) | 0.26 | 0.149 | 0.242 | 0.33 | 0.37 | 0.28 |
SNP ID | Gene | p-Value (R/NR) | p-Value (S/D/I) |
---|---|---|---|
rs10783219 | VDR | 0.6071 | 0.5330 |
rs7139166 | VDR | 0.4249 | 0.6209 |
rs731236 | VDR | 0.5133 | 0.0336 |
rs757343 | VDR | 0.6023 | 0.6926 |
rs10741657 | CYP2R1 | 0.3748 | 0.4870 |
rs10766197 | CYP2R1 | 0.7235 | 0.3820 |
rs12794714 | CYP2R1 | 0.7221 | 0.8857 |
rs1562902 | CYP2R1 | 0.3136 | 0.1389 |
rs10500804 | CYP2R1 | 0.7443 | 0.8867 |
rs1993116 | CYP2R1 | 0.6900 | 0.6161 |
rs7116978 | CYP2R1 | 0.0727 | 0.0163 |
rs10877012 | CYP27B1 | 0.7108 | 0.3583 |
rs4646536 | CYP27B1 | 0.8004 | 0.8265 |
rs703842 | CYP27B1 | 0.7845 | 0.7230 |
rs12785878 | DHCR7/NADSYN1 | 0.9386 | 0.9820 |
rs3829251 | DHCR7/NADSYN1 | 0.7488 | 0.4279 |
rs1155563 | GC | 0.9104 | 0.9904 |
rs12512631 | GC | 0.3288 | 0.1126 |
rs17467825 | GC | 0.0661 | 0.1188 |
rs222020 | GC | 0.4039 | 0.4397 |
rs2282679 | GC | 0.9068 | 0.7540 |
rs2882679 | GC | 0.4395 | 0.6346 |
rs3755967 | GC | 0.8826 | 0.5654 |
rs4588 | GC | 0.2287 | 0.1922 |
rs7041 | GC | 0.1961 | 0.2328 |
rs17219315 | CYP24A1 | 0.6713 | 0.3635 |
rs2244719 | CYP24A1 | 0.7235 | 0.3820 |
rs229624 | CYP24A1 | 0.8586 | 0.8796 |
rs2296241 | CYP24A1 | 0.3863 | 0.4631 |
rs2426496 | CYP24A1 | 0.4395 | 0.6346 |
rs4809960 | CYP24A1 | 0.5668 | 0.1768 |
rs6013897 | CYP24A1 | 0.7249 | 0.9156 |
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Tomei, S.; Singh, P.; Mathew, R.; Mattei, V.; Garand, M.; Alwakeel, M.; Sharif, E.; Al Khodor, S. The Role of Polymorphisms in Vitamin D-Related Genes in Response to Vitamin D Supplementation. Nutrients 2020, 12, 2608. https://doi.org/10.3390/nu12092608
Tomei S, Singh P, Mathew R, Mattei V, Garand M, Alwakeel M, Sharif E, Al Khodor S. The Role of Polymorphisms in Vitamin D-Related Genes in Response to Vitamin D Supplementation. Nutrients. 2020; 12(9):2608. https://doi.org/10.3390/nu12092608
Chicago/Turabian StyleTomei, Sara, Parul Singh, Rebecca Mathew, Valentina Mattei, Mathieu Garand, Mariam Alwakeel, Elham Sharif, and Souhaila Al Khodor. 2020. "The Role of Polymorphisms in Vitamin D-Related Genes in Response to Vitamin D Supplementation" Nutrients 12, no. 9: 2608. https://doi.org/10.3390/nu12092608