The Significance of VDR Genetic Polymorphisms in the Etiology of Preeclampsia in Pregnant Polish Women
Abstract
:1. Introduction
2. Materials and Methods
2.1. Subjects
2.2. Genotyping
2.3. Statistical Analysis
3. Results
3.1. Baseline Demographics and Clinical Characteristics of Study Population
3.2. Associations between SNPs and Preeclampsia Risk
3.3. Association between VDR Gene Variants and Blood Pressure
3.4. Linkage Disequilibrium and Haplotype Analysis of VDR SNPs
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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SNP | Chromosome Position * | Localization | Function | Alleles | Genomic Positions ** |
---|---|---|---|---|---|
rs2228570 (FokI) | chr12:47879112 | Exon 2 | Met-Thr | C>T | g.30920T>C |
rs1544410 (BsmI) | chr12:47846052 | Intron 8 | Non-coding | G>A | g.63980G>A |
rs7975232 (ApaI) | chr12:47845054 | Intron 8 | Non-coding | T>G | g.64978G>T |
rs731236 (TaqI) | chr12:47844974 | Exon 9 | Ile-Ile | T>C | g.65058T>C |
Variables | Preeclampsia n = 122 | Controls n = 184 | p |
---|---|---|---|
Maternal age (years), mean ± SD | 30.12 ± 5.52 | 30.58 ± 4.41 | 0.4507 |
Gestational age (weeks), mean ± SD | 33.72 ± 3.52 | 39.01 ± 1.21 | <0.001 |
Systolic blood pressure (mmHg), mean ± SD | 171.04 ± 19.27 | 102.31 ± 9.83 | <0.001 |
Diastolic blood pressure (mmHg), mean ± SD | 106.61 ± 12.89 | 64.97 ± 7,69 | <0.001 |
Pre-pregnancy BMI (kg/m2), mean ± SD | 24.56 ±.6.97 | 20.90 ± 1.97 | <0.001 |
Post-pregnancy BMI (kg/m2), mean ± SD | 30.40 ± 5.30 | 26.24 ± 2.60 | <0.001 |
Caesarean section, N (%) | 110 (90.16) | 61 (33.15) | <0.001 * |
Primipara, N (%) | 75 (61.48) | 72 (39.13) | 0.0001 * |
Infant birthweight (g), mean ± SD | 1887.95 ± 841.64 | 3417.66 ± 428.15 | <0.001 |
1-min Apgar score, median (IQR) | 8.00 (6.00–9.75) | 10.00 (10.00–10.00) | <0.001 # |
5-min Apgar score, median (IQR) | 9.00 (8.00–10.00) | 10.00 (10.00–10.00) | <0.001 # |
Variables | EOPE n = 57 | LOPE n = 65 | p |
---|---|---|---|
Maternal age (years), mean ± SD | 29.70 ± 5.49 | 30.50 ± 5.57 | 0.4298 |
Gestational age (weeks), mean ± SD | 30.60 ± 2.09 | 36.54 ± 1.69 | <0.001 |
Systolic blood pressure (mmHg), mean ± SD | 175.65 ± 19.51 | 166.97 ± 18.26 | 0.0171 |
Diastolic blood pressure (mmHg), mean ± SD | 107.44 ± 13.53 | 105.88 ± 12.37 | 0.5268 |
Pre-pregnancy BMI (kg/m2), mean ± SD | 24.46 ± 5.72 | 24.65 ± 7.93 | 0.8859 |
Post-pregnancy BMI (kg/m2), mean ± SD | 30.02 ± 4.19 | 30.74 ± 6.12 | 0.4660 |
Caesarean section, N (%) | 56 (98.25%) | 52 (80.00%) | 0.0171 ** |
Primipara, N (%) | 35 (61.40%) | 40 (61.54%) | 0.9878 * |
Infant birthweight (g), mean ± SD | 1336.11 ± 433.69 | 2403.61 ± 803.82 | <0.001 |
1-min Apgar score, median (IQR) | 7.00 (4.00–8.00) | 9.00 (8.00–10.00) | <0.001 # |
5-min Apgar score, median (IQR) | 8.00 (7.00–9.00) | 10.00 (9.00–10.00) | <0.001 # |
ALT (IU/L), mean ± SD | 53.83 ± 58.51 | 23.08 ± 17.49 | 0.0411 |
AST (IU/L), mean ± SD | 52.17 ± 52.50 | 25.50 ± 16.80 | 0.0492 |
Urea (mg/dL), mean ± SD | 32.42 ± 13.65 | 29.59 ± 14.00 | 0.2740 |
Uremic acid (mg/dL), mean ± SD | 6.74 ± 1.49 | 6.35 ± 1.16 | 0.1198 |
Total protein (g/dL), mean ± SD | 5.47 ± 0.56 | 5.81± 0.78 | 0.0089 |
Creatinine (mg/dL), mean ± SD | 0.81 ± 0.26 | 0.76 ± 0.30 | 0.5558 |
Proteinuria (mg/dL), mean ± SD | 365.76 ± 185.91 | 195.07 ± 165.32 | <0.001 |
Proteinuria (g/24 h), mean ± SD | 4.57 ± 2.92 | 2.92 ± 3.64 | 0.1680 |
SNP | Alleles | Preeclampsia n = 244 | Controls n = 368 | p | p Corr. | ||
---|---|---|---|---|---|---|---|
MAF n (Frequency) | HWE p | MAF n (Frequency) | HWE p | ||||
rs2228570 (FokI) | C>T | 118 (0.484) | 0.595 | 182 (0.495) | 0.140 | 0.791 | 1.000 |
rs1544410 (BsmI) | G>A | 114 (0.467) | 0.021 | 130 (0.353) | 0.104 | 0.005 | 0.020 |
rs7975232 (ApaI) | T>G | 107 (0.439) | 0.865 | 191 (0.519) | 0.448 | 0.051 | 0.204 |
rs731236 (TaqI) | T>C | 101 (0.414) | 0.971 | 122 (0.332) | 0.554 | 0.038 | 0.152 |
SNP | Genotypes/Models | Preeclampsia n = 122 n (%) | Controls n = 184 n (%) | OR (95%CI) | p | padj. |
---|---|---|---|---|---|---|
rs2228570 (FokI) | CC | 34 (27.9) | 42 (22.8) | 1.00 | 0.3897 | 0.5040 |
CT | 58 (47.5) | 102 (55.4) | 1.42 (0.82–2.48) | |||
TT | 30 (24.6) | 40 (21.7) | 1.08 (0.56–2.08) | |||
Dominant | 88 (72.1) | 142 (77.2) | 1.31 (0.77–2.21) | 0.3194 | 0.5383 | |
Recessive | 92 (75.4) | 144 (78.3) | 0.85 (0.50–1.46) | 0.5620 | 0.4498 | |
rs1544410 (BsmI) | GG | 41 (33.6) | 82 (44.6) | 1.00 | 0.0263 | 0.0113 |
GA | 48 (39.3) | 74 (40.2) | 0.77 (0.46–1.30) | |||
AA | 33 (27.0) | 28 (15.2) | 0.42 (0.23–0.79) | |||
Dominant | 81 (66.4) | 102 (55.4) | 0.63 (0.39–1.01) | 0.0545 | 0.0334 | |
Recessive | 89 (73.0) | 156 (84.8) | 0.48 (0.27–0.85) | 0.0119 | 0.0048 | |
rs7975232 (ApaI) | TT | 38 (31.1) | 40 (21.7) | 1.00 | 0.1304 | 0.0765 |
TG | 61 (50.0) | 97 (52.7) | 1.51 (0.87–2.61) | |||
GG | 23 (18.9) | 47 (25.5) | 1.94 (1.00–3.79) | |||
Dominant | 84 (68.9) | 144 (78.3) | 1.63 (0.97–2.74) | 0.0660 | 0.0425 | |
Recessive | 99 (81.1) | 137 (74.5) | 1.48 (0.84–2.59) | 0.1688 | 0.1064 | |
rs731236 (TaqI) | TT | 42 (34.4) | 84 (45.7) | 1.00 | 0.1171 | 0.0830 |
TC | 59 (48.4) | 78 (42.4) | 0.66 (0.40–1.09) | |||
CC | 21 (17.2) | 22 (12.0) | 0.52 (0.26–1.06) | |||
Dominant | 80 (65.6) | 100 (54.3) | 0.63 (0.39–1.00) | 0.0498 | 0.0375 | |
Recessive | 101 (82.8) | 162 (88.0) | 0.65 (0.34–1.25) | 0.1987 | 0.1353 |
SNP | Genotypes/ Models | Controls (n = 184) n (%) | EOPE (n = 57) n (%) | OR (95%CI) | p | padj. | LOPE (n = 65) n (%) | OR (95%CI) | p | padj. |
---|---|---|---|---|---|---|---|---|---|---|
rs2228570 (FokI) | CC | 42 (22.8) | 14 (24.6) | 1.00 | 0.5173 | 0.2164 | 20 (30.8) | 1.00 | 0.4240 | 0.4995 |
CT | 102 (55.4) | 27 (47.4) | 1.26 (0.60–2.64) | 31 (47.7) | 1.57 (0.80–3.05) | |||||
TT | 40 (21.7) | 16 (28.1) | 0.83 (0.36–1.93) | 14 (21.5) | 1.36 (0.61–3.05) | |||||
Dominant | 142 (77.2) | 43 (75.4) | 1.10 (0.55–2.20) | 0.7873 | 0.6852 | 45 (69.2) | 1.50 (0.80–2.82) | 0.2097 | 0.2387 | |
Recessive | 144 (78.3) | 41 (71.9) | 0.71 (0.36–1.40) | 0.3299 | 0.0815 | 51 (78.5) | 1.01 (0.51–2.01) | 0.9731 | 0.7277 | |
rs1544410 (BsmI) | GG | 82 (44.6) | 17 (29.8) | 1.00 | 0.0913 | 0.0464 | 24 (36.9) | 1.00 | 0.0563 | 0.0835 |
GA | 74 (40.2) | 26 (45.6) | 0.59 (0.30–1.17) | 22 (33.8) | 0.98 (0.51–1.90) | |||||
AA | 28 (15.2) | 14 (24.6) | 0.41 (0.18–0.95) | 19 (29.2) | 0.43 (0.21–0.90) | |||||
Dominant | 102 (55.4) | 40 (70.2) | 0.53 (0.28–1.00) | 0.0451 | 0.0498 | 41 (63.1) | 0.73 (0.41–1.30) | 0.2819 | 0.2465 | |
Recessive | 89 (73.0) | 43 (75.4) | 0.55 (0.27–1.14) | 0.1150 | 0.0305 | 46 (70.8) | 0.43 (0.22–0.85) | 0.0165 | 0.0263 | |
rs7975232 (ApaI) | TT | 40 (21.7) | 17 (29.8) | 1.00 | 0.0724 | 0.0356 | 21 (32.3) | 1.00 | 0.2232 | 0.2956 |
TG | 97 (52.7) | 33 (57.9) | 1.25 (0.63–2.49) | 28 (43.1) | 1.82 (0.93–3.57) | |||||
GG | 47 (25.5) | 7 (12.3) | 2.85 (1.08–7.57) | 16 (24.6) | 1.54 (0.71–3.35) | |||||
Dominant | 144 (78.3) | 40 (70.2) | 1.53 (0.79–2.98) | 0.2176 | 0.0911 | 44 (67.7) | 1.72 (0.92–3.22) | 0.0906 | 0.1258 | |
Recessive | 137 (74.5) | 50 (87.7) | 2.45 (1.04–5.78) | 0.0275 | 0.0185 | 49 (75.4) | 1.05 (0.54–2.02) | 0.8820 | 0.7935 | |
rs731236 (TaqI) | TT | 84 (45.7) | 18 (31.6) | 1.00 | 0.1613 | 0.1940 | 24 (36.9) | 1.00 | 0.2311 | 0.2636 |
TC | 78 (42.4) | 31 (54.4) | 0.54 (0.28–1.04) | 28 (43.1) | 0.80 (0.43–1.49) | |||||
CC | 22 (12.0) | 8 (14.0) | 0.59 (0.23–1.53) | 13 (20.0) | 0.48 (0.21–1.10) | |||||
Dominant | 100 (54.3) | 39 (68.4) | 0.55 (0.29–1.03) | 0.0574 | 0.0843 | 41 (63.1) | 0.70 (0.39–1.25) | 0.2199 | 0.2094 | |
Recessive | 162 (88.0) | 49 (86.0) | 0.83 (0.35–1.99) | 0.6815 | 0.2832 | 52 (80.0) | 0.54 (0.26–1.15) | 0.1200 | 0.1492 |
Mean ± SD (mmHg) | Codominant | Dominant | Recessive | ||||||
---|---|---|---|---|---|---|---|---|---|
AA | AB | BB | p | padj. | p | padj. | p | padj. | |
rs2228570 (FokI) | |||||||||
SBP | 131.27 ± 35.25 | 124.91 ± 34.93 | 132.15 ± 39.84 | 0.2736 | 0.3156 | 0.3920 | 0.6805 | 0.3070 | 0.2073 |
DBP | 81.87 ± 22.63 | 79.49 ± 22.15 | 81.90 ± 23.44 | 0.6620 | 0.6926 | 0.5860 | 0.9268 | 0.6048 | 0.4344 |
rs1544410 (BsmI) | |||||||||
SBP | 122.58 ± 33.55 | 127.69 ± 35.04 | 140.08 ± 41.00 | 0.0091 | 0.0033 | 0.0303 | 0.0172 | 0.0041 | 0.0015 |
DBP | 76.74 ± 21.47 | 81.03 ± 21.51 | 87.57 ± 25.00 | 0.0094 | 0.0026 | 0.0148 | 0.0073 | 0.0074 | 0.0020 |
rs7975232 (ApaI) | |||||||||
SBP | 136.84 ± 40.02 | 126.79 ± 34.90 | 121.54 ± 33.16 | 0.0319 | 0.0121 | 0.0151 | 0.0066 | 0.0855 | 0.0436 |
DBP | 85.34 ± 24.21 | 80.12 ± 22.00 | 76.54 ± 21.06 | 0.0591 | 0.0196 | 0.0345 | 0.0127 | 0.0870 | 0.0431 |
rs731236 (TaqI) | |||||||||
SBP | 122.56 ± 33.78 | 130.91 ± 36.45 | 135.71 ± 40.54 | 0.0641 | 0.0432 | 0.0263 | 0.0169 | 0.1451 | 0.1229 |
DBP | 76.90 ± 21.93 | 82.54 ± 21.82 | 85.45 ± 25.15 | 0.0448 | 0.0263 | 0.0171 | 0.0104 | 0.1352 | 0.0936 |
rs731236 | rs7975232 | rs1544410 | rs2228570 | Frequency (Overall) | Frequency (PE, Control) | χ2 | p Value | * p Value |
---|---|---|---|---|---|---|---|---|
T | G | G | 0.476 | 0.425, 0.510 | 4.325 | 0.0376 | 0.1705 | |
C | T | A | 0.356 | 0.410, 0.320 | 5.090 | 0.0241 | 0.0940 | |
T | T | G | 0.117 | 0.104, 0.125 | 0.654 | 0.4185 | 0.9505 | |
T | T | A | 0.038 | 0.045, 0.033 | 0.657 | 0.4178 | 0.9503 | |
G | G | C | 0.256 | 0.238, 0.269 | 0.734 | 0.3917 | 0.9553 | |
G | G | T | 0.225 | 0.188, 0.250 | 3.225 | 0.0725 | 0.3043 | |
T | A | C | 0.205 | 0.229, 0.190 | 1.347 | 0.2458 | 0.7768 | |
T | A | T | 0.188 | 0.226, 0.163 | 3.812 | 0.0509 | 0.2231 | |
T | G | T | 0.075 | 0.064, 0.082 | 0.708 | 0.4000 | 0.9594 | |
T | G | C | 0.045 | 0.043, 0.046 | 0.028 | 0.8660 | 1.0000 | |
T | G | G | C | 0.252 | 0.236, 0.262 | 0.502 | 0.4789 | 0.9959 |
T | G | G | T | 0.225 | 0.188, 0.249 | 3.091 | 0.0787 | 0.3742 |
C | T | A | C | 0.190 | 0.220, 0.170 | 2.419 | 0.1199 | 0.5402 |
C | T | A | T | 0.166 | 0.189, 0.150 | 1.598 | 0.2062 | 0.8185 |
T | T | G | T | 0.073 | 0.062, 0.080 | 0.673 | 0.4122 | 0.9892 |
T | T | G | C | 0.044 | 0.042, 0.045 | 0.046 | 0.8299 | 1.0000 |
T | T | A | T | 0.022 | 0.036, 0.013 | 3.618 | 0.0572 | 0.2777 |
T | T | A | C | 0.016 | 0.009, 0.020 | 1.015 | 0.3138 | 0.9720 |
4-Marker | SBP | DBP | |||||
---|---|---|---|---|---|---|---|
Haplotype | Frequency | Difference | 95%CI | p-Value | Difference | 95%CI | p-Value |
TGGC | 0.253 | 122.07 | Ref. | 76.31 | Ref. | ||
CTAC | 0.195 | 7.94 | (−2.24–18.13) | 0.1264 | 6.10 | (−0.37–12.57) | 0.0648 |
CTAT | 0.162 | 8.12 | (−1.55–17.79) | 0.0998 | 4.57 | (−1.42–10.56) | 0.1348 |
TTGT | 0.073 | 2.63 | (−10.61–15.86) | 0.6970 | 0.90 | (−7.42–9.21) | 0.8324 |
TGGT | 0.222 | -2.17 | (−11.79–7.45) | 0.6587 | −0.51 | (−6.72–5.71) | 0.8728 |
rare | 0.094 | 4.99 | (−6.38–16.37) | 0.3897 | 3.00 | (−4.29–10.28) | 0.4201 |
3-marker | |||||||
TGG | 0.475 | 120.21 | Ref. | 75.93 | Ref. | ||
CTA | 0.357 | 8.84 | (2.36–15.33) | 0.0075 | 5.53 | (1.50–9.56) | 0.0072 |
TTG | 0.114 | 3.59 | (−6.10–13.27) | 0.4677 | 1.38 | (−4.64–7.40) | 0.6529 |
rare | 0.053 | 7.76 | (−4.23–19.75) | 0.2046 | 4.12 | (−3.33–11.58) | 0.2780 |
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Magiełda-Stola, J.; Kurzawińska, G.; Ożarowski, M.; Karpiński, T.M.; Drews, K.; Seremak-Mrozikiewicz, A. The Significance of VDR Genetic Polymorphisms in the Etiology of Preeclampsia in Pregnant Polish Women. Diagnostics 2021, 11, 1698. https://doi.org/10.3390/diagnostics11091698
Magiełda-Stola J, Kurzawińska G, Ożarowski M, Karpiński TM, Drews K, Seremak-Mrozikiewicz A. The Significance of VDR Genetic Polymorphisms in the Etiology of Preeclampsia in Pregnant Polish Women. Diagnostics. 2021; 11(9):1698. https://doi.org/10.3390/diagnostics11091698
Chicago/Turabian StyleMagiełda-Stola, Justyna, Grażyna Kurzawińska, Marcin Ożarowski, Tomasz M. Karpiński, Krzysztof Drews, and Agnieszka Seremak-Mrozikiewicz. 2021. "The Significance of VDR Genetic Polymorphisms in the Etiology of Preeclampsia in Pregnant Polish Women" Diagnostics 11, no. 9: 1698. https://doi.org/10.3390/diagnostics11091698