The Association of Vitamin D and Its Pathway Genes’ Polymorphisms with Hypertensive Disorders of Pregnancy: A Prospective Cohort Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Participants
2.2. Collection of Data and Blood Sample
2.3. Measurement of 25(OH)D Concentrations
2.4. Data Extraction
2.5. Covariates Assessment
2.6. HDP Definition
2.7. SNP Selection and Genotyping
2.8. Statistical Analysis
3. Results
3.1. Subject Characteristics
3.2. The Association between 25(OH)D in Three Trimesters and HDP
3.3. The Association between SNP and HDP
3.4. The Interaction between Single SNP and VitD Deficiency in Three Trimesters on the Risk of HDP
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Hypertension in Pregnancy. Obstet. Gynecol. 2013, 122, 1122–1131. [Google Scholar] [CrossRef]
- Khan, K.S.; Wojdyla, D.; Say, L.; Gülmezoglu, A.M.; Van Look, P.F. WHO analysis of causes of maternal death: A systematic review. Lancet 2006, 367, 1066–1074. [Google Scholar] [CrossRef]
- Say, L.; Chou, D.; Gemmill, A.; Tunçalp, Ö.; Moller, A.-B.; Daniels, J.; Gülmezoglu, A.M.; Temmerman, M.; Alkema, L. Global causes of maternal death: A WHO systematic analysis. Lancet Glob. Health 2014, 2, E323–E333. [Google Scholar] [CrossRef] [Green Version]
- Theilen, L.H.; Meeks, H.; Fraser, A.; Esplin, M.S.; Smith, K.R.; Varner, M.W. Long-term mortality risk and life expectancy following recurrent hypertensive disease of pregnancy. Am. J. Obstet. Gynecol. 2018, 219, 107.e1–107.e6. [Google Scholar] [CrossRef] [Green Version]
- Visintin, C.; Mugglestone, M.A.; Almerie, M.Q.; Nherera, L.M.; James, D.; Walkinshaw, S. On behalf of the Guideline Development Group Management of hypertensive disorders during pregnancy: Summary of NICE guidance. BMJ 2010, 341, c2207. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rana, S.; Lemoine, E.; Granger, J.P.; Karumanchi, S.A. Preeclampsia: Pathophysiology, Challenges, and Perspectives. Circ. Res. 2019, 124, 1094–1112. [Google Scholar] [CrossRef] [PubMed]
- Adela, R.; Borkar, R.M.; Mishra, N.; Bhandi, M.M.; Vishwakarma, G.; Varma, B.A.; Ragampeta, S.; Banerjee, S.K. Lower Serum Vitamin D Metabolite Levels in Relation to Circulating Cytokines/Chemokines and Metabolic Hormones in Pregnant Women with Hypertensive Disorders. Front. Immunol. 2017, 8, 273. [Google Scholar] [CrossRef] [Green Version]
- Rezavand, N.; Tabarok, S.; Rahimi, Z.; Vaisi-Raygani, A.; Mohammadi, E.; Rahimi, Z. The effect of VDR gene polymorphisms and vitamin D level on blood pressure, risk of preeclampsia, gestational age, and body mass index. J. Cell. Biochem. 2018, 120, 6441–6448. [Google Scholar] [CrossRef]
- Zhang, J.Y.; Lucey, A.J.; Horgan, R.; Kenny, L.C.; Kiely, M. Impact of pregnancy on vitamin D status: A longitudinal study. Br. J. Nutr. 2014, 112, 1081–1087. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ganguly, A.; Tamblyn, J.A.; Finn-Sell, S.; Chan, S.; Westwood, M.; Gupta, J.; Kilby, M.D.; Gross, S.; Hewison, M. Vitamin D, the placenta and early pregnancy: Effects on trophoblast function. J. Endocrinol. 2018, 236, R93–R103. [Google Scholar] [CrossRef]
- Weisman, Y.; Harell, A.; Edelstein, S.; David, M.; Spirer, Z.; Golander, A. 1α, 25-Dihydroxyvitamin D3, and 24,25-dihydroxyvitamin D3 in vitro synthesis by human decidua and placenta. Nature 1979, 281, 317–319. [Google Scholar] [CrossRef]
- Zehnder, D.; Evans, K.N.; Kilby, M.D.; Bulmer, J.N.; Innes, B.A.; Stewart, P.M.; Hewison, M. The Ontogeny of 25-Hydroxyvitamin D3 1α-Hydroxylase Expression in Human Placenta and Decidua. Am. J. Pathol. 2002, 161, 105–114. [Google Scholar] [CrossRef]
- Karras, S.N.; Wagner, C.L.; Castracane, V.D. Understanding vitamin D metabolism in pregnancy: From physiology to pathophysiology and clinical outcomes. Metabolism 2018, 86, 112–123. [Google Scholar] [CrossRef] [PubMed]
- De-Regil, L.M.; Palacios, C.; Lombardo, L.K.; Pena-Rosas, J.P. Vitamin D supplementation for women during pregnancy. Cochrane Database Syst. Rev. 2016, 1, CD008873. [Google Scholar]
- Palacios, C.; Kostiuk, L.K.; Pena-Rosas, J.P. Vitamin D supplementation for women during pregnancy. Cochrane Database Syst. Rev. 2019, 7, CD008873. [Google Scholar] [CrossRef]
- Barebring, L.; O’Connell, M.; Winkvist, A.; Johannsson, G.; Augustin, H. Serum cortisol and vitamin D status are independently associated with blood pressure in pregnancy. J. Steroid Biochem. Mol. Biol. 2019, 189, 259–264. [Google Scholar] [CrossRef]
- Magnus, M.C.; Miliku, K.; Bauer, A.; Engel, S.M.; Felix, J.F.; Jaddoe, V.W.V.; ALawlor, D.; London, S.J.; Magnus, P.; McGinnis, R.; et al. Vitamin D and risk of pregnancy related hypertensive disorders: Mendelian randomisation study. BMJ 2018, 361, k2167. [Google Scholar] [CrossRef] [Green Version]
- Barry, E.L.; Rees, J.R.; Peacock, J.L.; Mott, L.A.; Amos, C.I.; Bostick, R.M.; Figueiredo, J.C.; Ahnen, D.J.; Bresalier, R.S.; Burke, C.A.; et al. Genetic variants in CYP2R1, CYP24A1, and VDR modify the efficacy of vitamin D3 supplementation for increasing serum 25-hydroxyvitamin D levels in a randomized controlled trial. J. Clin. Endocrinol. Metab. 2014, 99, E2133–E2137. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shao, B.; Mo, M.; Xin, X.; Jiang, W.; Wu, J.; Huang, M.; Wang, S.; Muyiduli, X.; Si, S.; Shen, Y.; et al. The interaction between prepregnancy BMI and gestational vitamin D deficiency on the risk of gestational diabetes mellitus subtypes with elevated fasting blood glucose. Clin. Nutr. 2020, 39, 2265–2273. [Google Scholar] [CrossRef]
- Holick, M.F.; Binkley, N.C.; Bischoff-Ferrari, H.A.; Gordon, C.M.; Hanley, D.A.; Heaney, R.P.; Murad, M.H.; Weaver, C.M. Endocrine Society. Evaluation, Treatment, and Prevention of Vitamin D Deficiency: An Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 2011, 96, 1911–1930. [Google Scholar] [CrossRef] [Green Version]
- Thorne, H.C.; Jones, K.H.; Peters, S.P.; Archer, S.N.; Dijk, D.-J. Daily and Seasonal Variation in the Spectral Composition of Light Exposure in Humans. Chrono Int. 2009, 26, 854–866. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhao, P.; Diao, Y.; You, L.; Wu, S.; Yang, L.; Liu, Y. The influence of basic public health service project on maternal health services: An interrupted time series study. BMC Public Health 2019, 19, 824–831. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Brown, M.A.; Magee, L.A.; Kenny, L.C.; Karumanchi, S.A.; McCarthy, F.P.; Saito, S.; Hall, D.R.; Warren, C.E.; Adoyi, G.; Ishaku, S.; et al. Hypertensive Disorders of Pregnancy: ISSHP Classification, Diagnosis, and Management Recommendations for International Practice. Hypertension 2018, 72, 24–43. [Google Scholar] [CrossRef] [Green Version]
- American College of Obstetricians and Gynecologists. Practice ACoO. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. International journal of gynaecology and obstetrics: The official organ of the International Federation of Gynaecology and Obstetrics. Obstet. Gynecol. 2002, 77, 67–75. [Google Scholar]
- Shao, B.; Jiang, S.; Muyiduli, X.; Wang, S.; Mo, M.; Li, M.; Wang, Z.; Yu, Y. Vitamin D pathway gene polymorphisms influenced vitamin D level among pregnant women. Clin. Nutr. 2018, 37, 2230–2237. [Google Scholar] [CrossRef]
- Wu, J.; Shao, B.; Xin, X.; Luo, W.; Mo, M.; Jiang, W.; Si, S.; Wang, S.; Shen, Y.; Yu, Y. Association of vitamin D pathway gene polymorphisms with vitamin D level during pregnancy was modified by season and vitamin D supplement. Clin. Nutr. 2020, 40, 3650–3660. [Google Scholar] [CrossRef]
- Li, W.; Jin, C.; Vaidya, A.; Wu, Y.; Rexrode, K.; Zheng, X.; Gurol, M.E.; Ma, C.; Wu, S.; Gao, X. Blood Pressure Trajectories and the Risk of Intracerebral Hemorrhage and Cerebral Infarction: A Prospective Study. Hypertension 2017, 70, 508–514. [Google Scholar] [CrossRef] [PubMed]
- Desquilbet, L.; Mariotti, F. Dose-response analyses using restricted cubic spline functions in public health research. Stat. Med. 2010, 29, 1037–1057. [Google Scholar] [CrossRef] [PubMed]
- Zhou, J.; Su, L.; Liu, M.; Liu, Y.; Cao, X.; Wang, Z.; Xiao, H. Associations between 25-hydroxyvitamin D levels and pregnancy outcomes: A prospective observational study in southern China. Eur. J. Clin. Nutr. 2014, 68, 925–930. [Google Scholar] [CrossRef] [Green Version]
- Bärebring, L.; Bullarbo, M.; Glantz, A.; Agelii, M.L.; Jagner; Ellis, J.; Hulthen, L.; Schoenmakers, I.; Augustin, H. Preeclampsia and Blood Pressure Trajectory during Pregnancy in Relation to Vitamin D Status. PLoS ONE 2016, 11, e0152198. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schneuer, F.J.; Roberts, C.L.; Guilbert, C.; Simpson, J.M.; Algert, C.S.; Khambalia, A.Z.; Tasevski, V.; Ashton, A.W.; Morris, J.M.; Nassar, N. Effects of maternal serum 25-hydroxyvitamin D concentrations in the first trimester on subsequent pregnancy outcomes in an Australian population. Am. J. Clin. Nutr. 2014, 99, 287–295. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- O’Callaghan, K.M.; Kiely, M. Systematic Review of Vitamin D and Hypertensive Disorders of Pregnancy. Nutrients 2018, 10, 294. [Google Scholar] [CrossRef] [Green Version]
- Wang, T.J.; Zhang, F.; Richards, J.B.; Kestenbaum, B.; van Meurs, J.B.; Berry, D.; Kiel, D.P.; Streeten, E.A.; Ohlsson, C.; Koller, D.L.; et al. Common genetic determinants of vitamin D insufficiency: A genome-wide association study. Lancet 2010, 376, 180–188. [Google Scholar] [CrossRef] [Green Version]
- Knabl, J.; Vattai, A.; Ye, Y.; Jueckstock, J.; Hutter, S.; Kainer, F.; Mahner, S.; Jeschke, U. Role of Placental VDR Expression and Function in Common Late Pregnancy Disorders. Int. J. Mol. Sci. 2017, 18, 2340. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sakaki, T.; Kagawa, N.; Yamamoto, K.; Inouye, K. Metabolism of vitamin D3 by cytochromes P450. Front. Biosci. 2005, 10, 119–134. [Google Scholar]
- Bao, Q.; Wang, D.; Zhang, Y.; Bao, L.; Jia, H. The Impact of CYP24A1 Polymorphisms on Hypertension Susceptibility. Kidney Blood Press. Res. 2020, 45, 28–37. [Google Scholar] [CrossRef]
- Wang, L.; Chu, A.; Buring, J.E.; Ridker, P.M.; Chasman, D.I.; Sesso, H.D. Common Genetic Variations in the Vitamin D Pathway in Relation to Blood Pressure. Am. J. Hypertens. 2014, 27, 1387–1395. [Google Scholar] [CrossRef] [Green Version]
- Marzolo, M.-P.; Farfán, P. New Insights into the Roles of Megalin/LRP2 and the Regulation of its Functional Expression. Biol. Res. 2011, 44, 89–105. [Google Scholar] [CrossRef] [Green Version]
- Norman, A.W. 1α,25(OH)2 Vitamin D3Vitamin D Nuclear Receptor (VDR) and Plasma Vitamin D-Binding Protein (DBP) Structures and Ligand Shape Preferences for Genomic and Rapid Biological Responses; Elsevier Inc.: Amsterdam, The Netherlands, 2008. [Google Scholar]
- Bikle, D.D.; Malmstroem, S.; Schwartz, J. Current Controversies: Are Free Vitamin Metabolite Levels a More Accurate Assessment of Vitamin D Status than Total Levels? Endocrinol. Metab. Clin. N. Am. 2017, 46, 901–918. [Google Scholar] [CrossRef]
- Mekbeb, T. The association of serum proteins with preeclampsia. Ethiop. Med. J. 1990, 28, 1–30. [Google Scholar]
- Naidoo, Y.; Moodley, J.; Ramsuran, V.; Naicker, T. Polymorphisms within vitamin D binding protein gene within a Preeclamptic South African population. Hypertens. Pregnancy 2019, 38, 260–267. [Google Scholar] [CrossRef]
- Powe, C.E.; Seely, E.W.; Rana, S.; Bhan, I.; Ecker, J.; Karumanchi, S.A.; Thadhani, R. First trimester vitamin D, vitamin D binding protein, and subsequent preeclampsia. Hypertension 2010, 56, 758–763. [Google Scholar] [CrossRef] [Green Version]
- Wang, S.; Xin, X.; Luo, W.; Mo, M.; Si, S.; Shao, B.; Shen, Y.; Cheng, H.; Yu, Y. Association of vitamin D and gene variants in the vitamin D metabolic pathway with preterm birth. Nutrition 2021, 89, 111349. [Google Scholar] [CrossRef] [PubMed]
- Phoswa, W.N. Dopamine in the Pathophysiology of Preeclampsia and Gestational Hypertension: Monoamine Oxidase (MAO) and Catechol-O-methyl Transferase (COMT) as Possible Mechanisms. Oxidative Med. Cell. Longev. 2019, 2019, 1–8. [Google Scholar] [CrossRef] [PubMed]
- Mammaro, A.; Carrara, S.; Cavaliere, A.; Ermito, S.; Dinatale, A.; Pappalardo, E.M.; Militello, M.; Pedata, R. Hypertensive disorders of pregnancy. J. Prenat. Med. 2009, 3, 1–5. [Google Scholar] [PubMed]
Variables | Non-HDP (N = 3594) | HDP (N = 105) | p |
---|---|---|---|
Mean ± SD | |||
Age, years | 28.67 ± 3.64 | 29.30 ± 3.95 | 0.0811 |
Pre-pregnancy BMI, kg/m2 | 21.16 ± 2.91 | 23.62 ± 4.05 | <0.0001 |
T1 (N = 3302) | |||
Weight gain, kg | 0.01 ± 0.17 | 0.02 ± 0.14 | 0.3841 |
SBP, mmHg | 103.53 ± 9.31 | 112.21 ± 10.58 | <0.0001 |
DBP, mmHg | 68.35 ± 6.67 | 74.48 ± 5.99 | <0.0001 |
25(OH)D, ng/mL | 17.85 ± 8.38 | 17.70 ± 7.10 | 0.8629 |
T2 (N = 2479) | |||
Weight gain, kg | 5.61 ± 3.82 | 6.25 ± 4.50 | 0.1971 |
SBP, mmHg | 107.17 ± 9.24 | 116.60 ± 14.44 | <0.0001 |
DBP, mmHg | 69.13 ± 7.82 | 76.61 ± 8.84 | <0.0001 |
25(OH)D, ng/mL | 23.28 ± 10.38 | 22.91 ± 9.60 | 0.7827 |
T3 (N = 1549) | |||
Weight gain, kg | 11.91 ± 3.73 | 11.20 ± 4.69 | 0.2181 |
SBP, mmHg | 108.86 ± 9.72 | 123.30 ± 15.68 | <0.0001 |
DBP, mmHg | 70.99 ± 7.38 | 82.43 ± 8.44 | <0.0001 |
25(OH)D, ng/mL | 26.53 ± 11.28 | 26.20 ± 11.01 | 0.8468 |
N (%) | |||
VitD deficiency at T1 a | 2176 (67.85) | 66 (69.47) | 0.7386 |
VitD deficiency at T2 b | 1067 (44.15) | 30 (48.39) | 0.5067 |
VitD deficiency at T3 c | 476 (31.63) | 13 (29.55) | 0.7696 |
Educational level | 0.1263 | ||
≤High school | 957 (26.63) | 35 (33.33) | |
>High school | 2637 (73.37) | 70 (66.67) | |
Gravity | 0.5389 | ||
1 | 1652 (45.97) | 43 (40.95) | |
≥2 | 1822 (50.70) | 59 (56.19) | |
Unknown | 120 (3.34) | 3 (2.86) | |
Parity | 0.4887 | ||
0 | 2015 (56.07) | 65 (61.90) | |
≥1 | 771 (21.45) | 20 (19.05) | |
Unknown | 808 (22.48) | 20 (19.05) |
Trimesters of 25(OH)D | N | SBP, mmHg | DBP, mmHg | ||
---|---|---|---|---|---|
β (se) | p | β (se) | p | ||
Blood pressure at T1 (N = 3302) | |||||
T1 | 3302 | −0.02 (0.02) | 0.3198 | 0.02 (0.01) | 0.2056 |
Blood pressure at T2 (N = 2479) | |||||
T1 | 2125 | −0.05 (0.02) | 0.0287 | −0.05 (0.02) | 0.0190 |
T2 | 2479 | 0.03 (0.02) | 0.1675 | −0.10 (0.02) | <0.0001 |
Blood pressure at T3 (N = 1549) | |||||
T1 | 1328 | 0.03 (0.03) | 0.2361 | −0.02 (0.02) | 0.3259 |
T2 | 1390 | 0.04 (0.03) | 0.1214 | −0.07 (0.02) | 0.0003 |
T3 | 1549 | 0.04 (0.02) | 0.0541 | −0.02 (0.02) | 0.2486 |
The Change of Trimesters | N | The Change of 25(OH)D Levels, ng/mL * | SBP, mmHg | DBP, mmHg | ||
---|---|---|---|---|---|---|
β (se) | p | β (se) | p | |||
Blood pressure at T2 (N = 2479) | ||||||
Between T1 and T2 | 2125 | 3.50 (84.59) | 0.03 (0.02) | 0.1217 | −0.11 (0.02) | <0.0001 |
Blood pressure at T3 (N = 1549) | ||||||
Between T1 and T2 | 1212 | 2.40 (81.27) | 0.03 (0.03) | 0.3142 | −0.11 (0.02) | <0.0001 |
Between T1 and T3 | 1328 | 6.59 (98.02) | 0.06 (0.03) | 0.0294 | −0.02 (0.02) | 0.3516 |
Between T2 and T3 | 1390 | 3.40 (87.23) | 0.02 (0.03) | 0.3662 | 0.04 (0.02) | 0.0405 |
Trajectory of VitD | N (%) | SBP, mmHg | DBP, mmHg | ||
---|---|---|---|---|---|
β (se) | p | β (se) | p | ||
Subgroup 1 | 621 (51.24) | Ref | Ref | ||
Subgroup 2 | 469 (38.70) | 0.48 (0.60) | 0.4216 | −1.13 (0.46) | 0.0137 |
Subgroup 3 | 122 (10.07) | 1.58 (0.98) | 0.1052 | −1.74 (0.74) | 0.0195 |
SNP | Genotypes | N | Case (%) | Crude Model | Adjusted Model * | ||
---|---|---|---|---|---|---|---|
OR (95%CI) | p | OR (95%CI) | p | ||||
CYP24A1 | |||||||
rs2209314 | TT | 941 | 28 (3.0) | Ref | Ref | ||
CT | 1309 | 38 (2.9) | 0.97 (0.59–1.60) | 0.9198 | 0.99 (0.60–1.64) | 0.9648 | |
CC | 443 | 4 (0.9) | 0.30 (0.10–0.85) | 0.024 | 0.30 (0.10–0.87) | 0.026 | |
rs2248137 | GG | 934 | 18 (1.9) | Ref | Ref | ||
GC | 453 | 20 (4.4) | 2.35 (1.23–4.49) | 0.0096 | 2.62 (1.32–5.21) | 0.0059 | |
CC | 643 | 19 (3.0) | 1.55 (0.81–2.98) | 0.1885 | 1.80 (0.92–3.53) | 0.0869 | |
rs2762934 | GG | 599 | 22 (3.7) | Ref | Ref | ||
GA | 119 | 5 (4.2) | 1.15 (0.43–3.10) | 0.7819 | 1.07 (0.38–3.00) | 0.9051 | |
AA | 7 | 1 (14.3) | 4.37 (0.50–37.88) | 0.1806 | 9.98 (1.06–94.04) | 0.0444 | |
rs6013897 | TT | 529 | 20 (3.8) | Ref | Ref | ||
AT | 172 | 8 (4.7) | 1.24 (0.54–2.87) | 0.6131 | 1.26 (0.53–3.02) | 0.5964 | |
AA | 22 | 1 (4.5) | 1.21 (0.16–9.46) | 0.8546 | 1.53 (0.19–12.57) | 0.6905 | |
rs6127118 | GG | 963 | 24 (2.5) | Ref | Ref | ||
AG | 1616 | 41 (2.5) | 1.02 (0.61–1.70) | 0.9439 | 0.96 (0.57–1.61) | 0.8736 | |
AA | 119 | 7 (5.9) | 2.45 (1.03–5.80) | 0.0426 | 2.38 (0.98–5.77) | 0.0542 | |
CYP27B1 | |||||||
rs10877012 | TT | 1125 | 27 (2.4) | Ref | Ref | ||
GT | 1204 | 32 (2.7) | 1.11 (0.66–1.87) | 0.6925 | 1.14 (0.67–1.93) | 0.6354 | |
GG | 360 | 12 (3.3) | 1.40 (0.70–2.80) | 0.3366 | 1.61 (0.80–3.25) | 0.1856 | |
CYP3A4 | |||||||
rs2242480 | CC | 1529 | 41 (2.7) | Ref | Ref | ||
CT | 1004 | 26 (2.6) | 0.96 (0.59–1.59) | 0.8879 | 0.96 (0.58–1.60) | 0.8885 | |
TT | 159 | 5 (3.1) | 1.18 (0.46–3.03) | 0.7329 | 1.37 (0.53–3.56) | 0.5164 | |
rs4646437 | GG | 530 | 22 (4.2) | Ref | Ref | ||
AG | 182 | 7 (3.8) | 0.92 (0.39–2.20) | 0.8576 | 0.83 (0.34–2.04) | 0.6868 | |
GC | |||||||
rs1155563 | TT | 951 | 29 (3.0) | Ref | Ref | ||
TC | 1290 | 31 (2.4) | 0.78 (0.47–1.31) | 0.3499 | 0.76 (0.45–1.29) | 0.3091 | |
CC | 450 | 11 (2.4) | 0.80 (0.39–1.61) | 0.5262 | 0.73 (0.36–1.50) | 0.3886 | |
rs12512631 | TT | 463 | 21 (4.5) | Ref | Ref | ||
CT | 241 | 7 (2.9) | 0.63 (0.26–1.50) | 0.2973 | 0.77 (0.31–1.89) | 0.5683 | |
CC | 18 | 1 (5.6) | 1.24 (0.16–9.75) | 0.8393 | 1.07 (0.13–8.84) | 0.9466 | |
rs16846876 | AA | 1274 | 38 (3.0) | Ref | Ref | ||
AT | 1133 | 25 (2.2) | 0.73 (0.44–1.22) | 0.2357 | 0.69 (0.41–1.16) | 0.1632 | |
TT | 292 | 9 (3.1) | 1.03 (0.49–2.16) | 0.9283 | 0.89 (0.41–1.93) | 0.7745 | |
rs17467825 | AA | 1254 | 37 (3.0) | Ref | Ref | ||
GA | 1150 | 29 (2.5) | 0.85 (0.52–1.39) | 0.5208 | 0.80 (0.48–1.32) | 0.3792 | |
GG | 299 | 6 (2.0) | 0.67 (0.28–1.61) | 0.375 | 0.54 (0.22–1.33) | 0.181 | |
rs2070741 | TT | 495 | 17 (3.4) | Ref | Ref | ||
GT | 213 | 8 (3.8) | 1.10 (0.47–2.58) | 0.8317 | 1.10 (0.46–2.66) | 0.8251 | |
GG | 18 | 3 (16.7) | 5.62 (1.49–21.28) | 0.011 | 4.77 (1.12–20.21) | 0.0341 | |
rs222020 | TT | 270 | 10 (3.7) | Ref | Ref | ||
CT | 344 | 12 (3.5) | 0.94 (0.40–2.21) | 0.8867 | 0.85 (0.35–2.07) | 0.7284 | |
CC | 110 | 6 (5.5) | 1.50 (0.53–4.23) | 0.4436 | 1.42 (0.49–4.15) | 0.5169 | |
rs2282679 | TT | 1254 | 36 (2.9) | Ref | Ref | ||
GT | 1141 | 30 (2.6) | 0.91 (0.56–1.49) | 0.7185 | 0.87 (0.52–1.43) | 0.5726 | |
GG | 306 | 6 (2.0) | 0.68 (0.28–1.62) | 0.3808 | 0.55 (0.22–1.35) | 0.1913 | |
rs2298849 | AA | 1120 | 27 (2.4) | Ref | Ref | ||
GA | 1219 | 38 (3.1) | 1.30 (0.79–2.15) | 0.3003 | 1.32 (0.79–2.20) | 0.2835 | |
GG | 366 | 7 (1.9) | 0.79 (0.34–1.83) | 0.5809 | 0.82 (0.35–1.90) | 0.6376 | |
rs2298850 | GG | 1229 | 35 (2.8) | Ref | Ref | ||
CG | 1151 | 29 (2.5) | 0.88 (0.54–1.45) | 0.621 | 0.84 (0.50–1.39) | 0.4891 | |
CC | 305 | 6 (2.0) | 0.68 (0.29–1.64) | 0.3967 | 0.55 (0.22–1.38) | 0.2051 | |
rs3755967 | CC | 1250 | 36 (2.9) | Ref | Ref | ||
CT | 1149 | 30 (2.6) | 0.90 (0.55–1.48) | 0.6875 | 0.86 (0.52–1.42) | 0.5515 | |
TT | 306 | 6 (2.0) | 0.67 (0.28–1.62) | 0.3768 | 0.54 (0.22–1.35) | 0.189 | |
rs4588 | GG | 1241 | 36 (2.9) | Ref | Ref | ||
GT | 1146 | 29 (2.5) | 0.87 (0.53–1.43) | 0.5789 | 0.83 (0.50–1.37) | 0.4576 | |
TT | 306 | 6 (2.0) | 0.67 (0.28–1.60) | 0.3679 | 0.54 (0.22–1.34) | 0.1819 | |
rs7041 | AA | 1445 | 39 (2.7) | Ref | Ref | ||
CA | 1061 | 28 (2.6) | 0.98 (0.60–1.60) | 0.9268 | 1.03 (0.62–1.70) | 0.9026 | |
CC | 195 | 4 (2.1) | 0.76 (0.27–2.14) | 0.5968 | 0.87 (0.30–2.48) | 0.7934 | |
LRP2 | |||||||
rs10210408 | CC | 895 | 22 (2.5) | Ref | Ref | ||
TC | 1325 | 40 (3.0) | 1.24 (0.73–2.09) | 0.4322 | 1.16 (0.68–1.99) | 0.5816 | |
TT | 486 | 10 (2.1) | 0.83 (0.39–1.78) | 0.6378 | 0.81 (0.38–1.74) | 0.5919 | |
rs2228171 | TT | 932 | 24 (2.6) | Ref | Ref | ||
CT | 394 | 15 (3.8) | 1.50 (0.78–2.89) | 0.2279 | 1.48 (0.75–2.94) | 0.2607 | |
CC | 301 | 8 (2.7) | 1.03 (0.46–2.32) | 0.9375 | 1.14 (0.50–2.61) | 0.7534 | |
rs2389557 | AA | 194 | 8 (4.1) | Ref | Ref | ||
GA | 363 | 12 (3.3) | 0.79 (0.32–1.98) | 0.6218 | 0.78 (0.31–2.00) | 0.6094 | |
GG | 166 | 9 (5.4) | 1.33 (0.50–3.54) | 0.5639 | 1.24 (0.45–3.42) | 0.6722 | |
rs2544381 | GG | 388 | 20 (5.2) | Ref | Ref | ||
CG | 284 | 7 (2.5) | 0.46 (0.19–1.12) | 0.0862 | 0.48 (0.19–1.18) | 0.108 | |
CC | 52 | 1 (1.9) | 0.36 (0.05–2.75) | 0.3249 | 0.37 (0.05–2.92) | 0.349 | |
rs2544390 | CC | 199 | 9 (4.5) | Ref | Ref | ||
CT | 370 | 14 (3.8) | 0.83 (0.35–1.95) | 0.6698 | 0.70 (0.29–1.71) | 0.4308 | |
TT | 154 | 5 (3.2) | 0.71 (0.23–2.16) | 0.5442 | 0.68 (0.22–2.15) | 0.5131 | |
rs4667591 | TT | 245 | 10 (4.1) | Ref | Ref | ||
GT | 347 | 11 (3.2) | 0.77 (0.32–1.84) | 0.5558 | 0.82 (0.33–2.03) | 0.671 | |
GG | 132 | 8 (6.1) | 1.52 (0.58–3.94) | 0.3929 | 1.68 (0.62–4.56) | 0.3081 | |
rs7600336 | CC | 236 | 8 (3.4) | Ref | Ref | ||
TC | 342 | 14 (4.1) | 1.22 (0.50–2.95) | 0.6643 | 1.10 (0.44–2.75) | 0.8428 | |
TT | 148 | 6 (4.1) | 1.20 (0.41–3.54) | 0.7357 | 1.30 (0.43–3.93) | 0.6374 | |
VDR | |||||||
rs10783219 | AA | 998 | 26 (2.6) | Ref | Ref | ||
TA | 1275 | 36 (2.8) | 1.09 (0.65–1.81) | 0.7512 | 1.03 (0.61–1.74) | 0.8982 | |
TT | 428 | 9 (2.1) | 0.80 (0.37–1.73) | 0.5753 | 0.76 (0.35–1.66) | 0.4869 | |
rs11568820 | CC | 219 | 6 (2.7) | Ref | Ref | ||
TC | 350 | 17 (4.9) | 1.81 (0.70–4.67) | 0.2182 | 1.93 (0.72–5.14) | 0.19 | |
TT | 153 | 5 (3.3) | 1.20 (0.36–4.00) | 0.7675 | 1.48 (0.43–5.14) | 0.5328 | |
rs2228570 | GG | 212 | 10 (4.7) | Ref | Ref | ||
GA | 364 | 15 (4.1) | 0.87 (0.38–1.97) | 0.7351 | 0.86 (0.37–2.00) | 0.7204 | |
AA | 148 | 3 (2.0) | 0.42 (0.11–1.55) | 0.191 | 0.41 (0.11–1.56) | 0.1905 | |
rs2238136 | CC | 483 | 19 (3.9) | Ref | Ref | ||
TC | 218 | 10 (4.6) | 1.17 (0.54–2.57) | 0.6879 | 1.16 (0.51–2.60) | 0.7259 | |
rs2853559 | GG | 319 | 16 (5.0) | Ref | Ref | ||
GA | 313 | 10 (3.2) | 0.62 (0.28–1.40) | 0.2531 | 0.68 (0.29–1.56) | 0.3599 | |
AA | 87 | 2 (2.3) | 0.45 (0.10–1.98) | 0.2875 | 0.40 (0.09–1.84) | 0.2418 | |
rs4334089 | GG | 227 | 7 (3.1) | Ref | Ref | ||
AG | 350 | 15 (4.3) | 1.41 (0.56–3.51) | 0.4637 | 1.45 (0.56–3.75) | 0.4397 | |
AA | 148 | 6 (4.1) | 1.33 (0.44–4.03) | 0.617 | 1.54 (0.49–4.85) | 0.4563 | |
rs7975232 | CC | 382 | 11 (2.9) | Ref | Ref | ||
CA | 285 | 15 (5.3) | 1.87 (0.85–4.14) | 0.121 | 1.84 (0.81–4.20) | 0.1458 | |
AA | 60 | 3 (5.0) | 1.78 (0.48–6.56) | 0.3894 | 1.77 (0.46–6.78) | 0.4031 |
SNP | Genotypes | VitD | T1 | T2 | T3 | |||
---|---|---|---|---|---|---|---|---|
N | OR (95%CI) | N | OR (95%CI) | N | OR (95%CI) | |||
CYP24A1 | ||||||||
rs2209314 | CC/CT | ≥20 | 545 | Ref | 724 | Ref | 557 | Ref |
TT | ≥20 | 316 | 1.60 (0.66–3.87) | 383 | 1.41 (0.65–3.08) | 294 | 1.86 (0.80–4.28) | |
CC/CT | <20 | 1026 | 1.18 (0.57–2.45) | 541 | 1.13 (0.53–2.40) | 260 | 1.20 (0.43–3.29) | |
TT | <20 | 560 | 1.52 (0.70–3.32) | 309 | 1.41 (0.62–3.18) | 145 | 1.04 (0.28–3.79) | |
Pinteraction | 0.8774 | 0.7996 | 0.5739 | |||||
rs2248137 | GG | ≥20 | 357 | Ref | 451 | Ref | 339 | Ref |
GC | ≥20 | 117 | 2.50 (0.81–7.73) | 111 | 4.45 (1.25–15.79) * | 106 | 3.81 (1.11–13.07) * | |
CC | ≥20 | 220 | 1.04 (0.32–3.31) | 269 | 3.90 (1.33–11.41) * | 195 | 2.22 (0.66–7.47) | |
GG | <20 | 480 | 0.77 (0.28–2.09) | 283 | 2.11 (0.67–6.63) | 131 | 1.17 (0.22–6.23) | |
GC | <20 | 317 | 1.80 (0.70–4.67) | 133 | 5.42 (1.71–17.23) * | 63 | 1.05 (0.12–9.51) | |
CC | <20 | 377 | 1.65 (0.64–4.26) | 171 | 1.17 (0.22–6.04) | 90 | 2.47 (0.56–10.81) | |
Pinteraction | 0.5195 | 0.1442 | 0.8045 | |||||
rs6127118 | GG | ≥20 | 288 | Ref | 405 | Ref | 316 | Ref |
AG/AA | ≥20 | 572 | 2.01 (0.66–6.10) | 702 | 0.83 (0.38–1.81) | 537 | 2.97 (0.99–8.88) | |
GG | <20 | 582 | 2.29 (0.77–6.87) | 291 | 0.77 (0.28–2.12) | 133 | 1.86 (0.40–8.58) | |
AG/AA | <20 | 1010 | 1.63 (0.56–4.77) | 558 | 1.12 (0.52–2.42) | 271 | 2.18 (0.62–7.65) | |
Pinteraction | 0.855 | 0.2332 | 0.5262 | |||||
CYP27B1 | ||||||||
rs10877012 | TT | ≥20 | 363 | Ref | 445 | Ref | 331 | Ref |
GT | ≥20 | 372 | 1.14 (0.40–3.23) | 510 | 1.24 (0.53–2.93) | 405 | 1.12 (0.42–2.94) | |
GG | ≥20 | 121 | 2.67 (0.86–8.29) | 151 | 1.84 (0.60–5.61) | 115 | 2.56 (0.83–7.85) | |
TT | <20 | 661 | 1.28 (0.52–3.15) | 361 | 1.08 (0.41–2.84) | 168 | 0.84 (0.21–3.27) | |
GT | <20 | 725 | 1.41 (0.59–3.41) | 370 | 1.26 (0.51–3.12) | 180 | 1.32 (0.41–4.21) | |
GG | <20 | 201 | 1.79 (0.58–5.49) | 114 | 2.80 (0.97–8.10) | 54 | 2.26 (0.45–11.45) | |
Pinteraction | 0.6139 | 0.4639 | 0.9865 | |||||
CYP3A4 | ||||||||
rs2242480 | CC | ≥20 | 490 | Ref | 644 | Ref | 504 | Ref |
CT | ≥20 | 314 | 0.89 (0.34–2.31) | 404 | 1.16 (0.51–2.64) | 293 | 1.08 (0.44–2.68) | |
TT | ≥20 | 54 | 1.74 (0.37–8.17) | 59 | 1.57 (0.35–7.15) | 52 | 2.47 (0.66–9.19) | |
CC | <20 | 899 | 1.04 (0.51–2.13) | 480 | 1.53 (0.75–3.13) | 247 | 1.25 (0.48–3.22) | |
CT | <20 | 604 | 1.16 (0.54–2.47) | 318 | 0.53 (0.17–1.61) | 142 | 0.51 (0.11–2.33) | |
TT | <20 | 87 | 1.52 (0.41–5.62) | 51 | 3.13 (0.85–11.47) | 17 | 3.30 (0.39–28.05) | |
Pinteraction | 0.7911 | 0.696 | 0.5117 | |||||
GC | ||||||||
rs1155563 | TT | ≥20 | 331 | Ref | 440 | Ref | 326 | Ref |
TC | ≥20 | 401 | 0.81 (0.31–2.11) | 498 | 1.04 (0.44–2.44) | 392 | 0.45 (0.17–1.15) | |
CC | ≥20 | 127 | 0.81 (0.21–3.09) | 167 | 1.31 (0.44–3.95) | 133 | 0.87 (0.27–2.80) | |
TT | <20 | 531 | 1.26 (0.55–2.88) | 272 | 1.70 (0.70–4.15) | 123 | 0.21 (0.03–1.65) | |
TC | <20 | 766 | 0.78 (0.34–1.80) | 403 | 1.02 (0.40–2.55) | 199 | 0.92 (0.33–2.52) | |
CC | <20 | 290 | 0.89 (0.33–2.42) | 172 | 0.87 (0.26–2.89) | 83 | 0.94 (0.25–3.54) | |
Pinteraction | 0.9456 | 0.5655 | 0.2934 | |||||
rs16846876 | AA | ≥20 | 437 | Ref | 557 | Ref | 419 | Ref |
AT | ≥20 | 366 | 1.22 (0.48–3.07) | 450 | 1.18 (0.52–2.70) | 353 | 0.34 (0.12–0.99) | |
TT | ≥20 | 58 | 1.31 (0.27–6.38) | 102 | 1.46 (0.43–4.97) | 81 | 1.83 (0.62–5.37) | |
AA | <20 | 714 | 1.65 (0.75–3.60) | 379 | 1.71 (0.77–3.79) | 168 | 0.51 (0.14–1.84) | |
AT | <20 | 672 | 0.87 (0.37–2.07) | 362 | 1.00 (0.40–2.51) | 182 | 1.00 (0.38–2.69) | |
TT | <20 | 206 | 1.12 (0.37–3.36) | 108 | 0.72 (0.15–3.38) | 55 | 0.48 (0.06–3.85) | |
Pinteraction | 0.4024 | 0.3482 | 0.8437 | |||||
rs17467825 | AA | ≥20 | 447 | Ref | 578 | Ref | 430 | Ref |
GA | ≥20 | 352 | 0.79 (0.31–1.99) | 437 | 1.06 (0.48–2.34) | 337 | 0.41 (0.15–1.07) | |
GG | ≥20 | 62 | 0.49 (0.06–3.95) | 94 | 0.59 (0.12–3.00) | 88 | 0.56 (0.13–2.33) | |
AA | <20 | 692 | 1.15 (0.55–2.38) | 347 | 1.55 (0.71–3.40) | 152 | 0.36 (0.08–1.61) | |
GA | <20 | 691 | 0.91 (0.43–1.93) | 383 | 0.84 (0.35–2.04) | 191 | 0.85 (0.32–2.25) | |
GG | <20 | 213 | 0.65 (0.21–1.98) | 121 | 0.81 (0.22–2.96) | 62 | 0.76 (0.17–3.48) | |
Pinteraction | 0.8118 | 0.8253 | 0.2029 | |||||
rs2282679 | TT | ≥20 | 449 | Ref | 578 | Ref | 429 | Ref |
GT | ≥20 | 349 | 0.81 (0.32–2.04) | 434 | 1.27 (0.57–2.80) | 336 | 0.42 (0.16–1.10) | |
GG | ≥20 | 63 | 0.47 (0.06–3.80) | 98 | 0.62 (0.12–3.11) | 89 | 0.56 (0.13–2.34) | |
TT | <20 | 688 | 1.10 (0.53–2.29) | 345 | 1.67 (0.75–3.71) | 153 | 0.36 (0.08–1.60) | |
GT | <20 | 689 | 0.97 (0.46–2.04) | 381 | 0.92 (0.37–2.25) | 188 | 0.87 (0.33–2.30) | |
GG | <20 | 217 | 0.65 (0.21–1.97) | 123 | 0.88 (0.24–3.22) | 63 | 0.76 (0.17–3.48) | |
Pinteraction | 0.7444 | 0.6979 | 0.2075 | |||||
rs2298849 | AA | ≥20 | 332 | Ref | 430 | Ref | 346 | Ref |
GA | ≥20 | 411 | 3.12 (1.02–9.59) * | 511 | 0.92 (0.41–2.05) | 386 | 0.93 (0.38–2.27) | |
GG | ≥20 | 120 | 1.36 (0.24–7.60) | 170 | 0.43 (0.09–1.95) | 124 | 1.23 (0.37–4.10) | |
AA | <20 | 692 | 2.29 (0.77–6.85) | 378 | 0.72 (0.29–1.82) | 173 | 1.01 (0.33–3.11) | |
GA | <20 | 700 | 2.33 (0.78–6.95) | 362 | 1.28 (0.57–2.87) | 178 | 1.25 (0.41–3.82) | |
GG | <20 | 204 | 1.94 (0.51–7.40) | 111 | 1.01 (0.28–3.70) | 54 | — | |
Pinteraction | 0.5918 | 0.1481 | 0.4554 | |||||
rs2298850 | GG | ≥20 | 441 | Ref | 564 | Ref | 416 | Ref |
CG | ≥20 | 354 | 0.77 (0.31–1.95) | 437 | 1.34 (0.60–3.01) | 341 | 0.41 (0.15–1.10) | |
CC | ≥20 | 63 | 0.46 (0.06–3.71) | 99 | 0.66 (0.13–3.33) | 89 | 0.56 (0.13–2.37) | |
GG | <20 | 672 | 1.04 (0.50–2.20) | 339 | 1.83 (0.81–4.12) | 150 | 0.38 (0.09–1.70) | |
CG | <20 | 694 | 0.90 (0.42–1.91) | 385 | 0.85 (0.33–2.20) | 191 | 0.75 (0.26–2.12) | |
CC | <20 | 215 | 0.64 (0.21–1.96) | 122 | 0.94 (0.25–3.50) | 63 | 0.79 (0.17–3.65) | |
Pinteraction | 0.759 | 0.5603 | 0.2452 | |||||
rs3755967 | CC | ≥20 | 448 | Ref | 575 | Ref | 427 | Ref |
CT | ≥20 | 351 | 0.80 (0.32–2.01) | 438 | 1.25 (0.57–2.76) | 340 | 0.41 (0.16–1.08) | |
TT | ≥20 | 63 | 0.47 (0.06–3.78) | 98 | 0.61 (0.12–3.10) | 89 | 0.56 (0.13–2.32) | |
CC | <20 | 685 | 1.09 (0.52–2.29) | 345 | 1.66 (0.75–3.69) | 153 | 0.36 (0.08–1.58) | |
CT | <20 | 695 | 0.96 (0.46–2.02) | 383 | 0.91 (0.37–2.24) | 189 | 0.86 (0.33–2.27) | |
TT | <20 | 217 | 0.64 (0.21–1.96) | 123 | 0.87 (0.24–3.20) | 63 | 0.75 (0.16–3.45) | |
Pinteraction | 0.7354 | 0.7072 | 0.2031 | |||||
rs4588 | GG | ≥20 | 448 | Ref | 571 | Ref | 422 | Ref |
GT | ≥20 | 348 | 0.81 (0.32–2.05) | 439 | 1.23 (0.56–2.72) | 339 | 0.40 (0.15–1.07) | |
TT | ≥20 | 64 | 0.45 (0.06–3.57) | 98 | 0.60 (0.12–3.05) | 90 | 0.54 (0.13–2.24) | |
GG | <20 | 676 | 1.11 (0.53–2.32) | 341 | 1.66 (0.75–3.70) | 149 | 0.37 (0.08–1.65) | |
GT | <20 | 696 | 0.91 (0.43–1.93) | 382 | 0.80 (0.31–2.05) | 192 | 0.70 (0.25–1.98) | |
TT | <20 | 215 | 0.65 (0.21–1.99) | 124 | 0.84 (0.23–3.11) | 63 | 0.75 (0.16–3.46) | |
Pinteraction | 0.8164 | 0.6081 | 0.2578 | |||||
rs7041 | AA | ≥20 | 423 | Ref | 573 | Ref | 454 | Ref |
CA | ≥20 | 358 | 2.46 (0.96–6.32) | 453 | 0.92 (0.42–2.04) | 337 | 0.65 (0.27–1.58) | |
CC | ≥20 | 82 | 0.97 (0.12–8.11) | 84 | 0.55 (0.07–4.25) | 63 | 0.50 (0.06–3.91) | |
AA | <20 | 892 | 2.03 (0.87–4.75) | 478 | 1.15 (0.55–2.40) | 226 | 0.80 (0.30–2.13) | |
CA | <20 | 612 | 1.21 (0.46–3.14) | 316 | 1.04 (0.43–2.50) | 158 | 0.61 (0.17–2.18) | |
CC | <20 | 88 | 2.18 (0.54–8.77) | 56 | — | 21 | — | |
Pinteraction | 0.2275 | 0.8097 | 0.8926 | |||||
LRP2 | ||||||||
rs10210408 | CC | ≥20 | 289 | Ref | 354 | Ref | 287 | Ref |
TC | ≥20 | 418 | 1.75 (0.60–5.10) | 558 | 1.45 (0.58–3.62) | 415 | 0.69 (0.29–1.62) | |
TT | ≥20 | 155 | 1.56 (0.40–6.00) | 199 | 1.25 (0.39–4.03) | 154 | 0.30 (0.07–1.42) | |
CC | <20 | 526 | 1.83 (0.66–5.12) | 294 | 1.10 (0.36–3.33) | 127 | 0.41 (0.09–1.94) | |
TC | <20 | 782 | 1.64 (0.61–4.40) | 399 | 1.96 (0.79–4.89) | 214 | 0.86 (0.32–2.31) | |
TT | <20 | 290 | 1.16 (0.34–3.91) | 158 | 0.64 (0.13–3.15) | 64 | 0.44 (0.06–3.55) | |
Pinteraction | 0.497 | 0.9331 | 0.3864 | |||||
rs2228171 | TT | ≥20 | 291 | Ref | 374 | Ref | 292 | Ref |
CT | ≥20 | 92 | 0.97 (0.19–4.86) | 89 | 2.33 (0.65–8.38) | 63 | 0.98 (0.21–4.70) | |
CC | ≥20 | 84 | 1.61 (0.39–6.59) | 104 | 0.91 (0.19–4.49) | 74 | 0.37 (0.05–3.00) | |
TT | <20 | 548 | 1.21 (0.48–3.07) | 294 | 1.06 (0.36–3.16) | 140 | 0.60 (0.16–2.29) | |
CT | <20 | 286 | 1.68 (0.62–4.56) | 96 | 2.12 (0.59–7.56) | 60 | — | |
CC | <20 | 194 | 1.26 (0.38–4.14) | 111 | 2.37 (0.67–8.41) | 59 | 1.22 (0.25–5.97) | |
Pinteraction | 0.9483 | 0.4054 | 0.5358 | |||||
rs2389557 | AA/GA | ≥20 | 113 | Ref | 102 | Ref | 87 | Ref |
GG | ≥20 | 37 | 2.15 (0.18–25.61) | 35 | 1.66 (0.22–12.36) | 26 | 2.11 (0.21–20.73) | |
AA/GA | <20 | 433 | 2.50 (0.55–11.48) | 156 | 1.04 (0.20–5.46) | 100 | 0.55 (0.07–4.57) | |
GG | <20 | 125 | 3.57 (0.70–18.10) | 33 | 7.09 (1.21–41.47) | 18 | — | |
Pinteraction | 0.7002 | 0.8493 | 0.2569 | |||||
rs4667591 | TT/GT | ≥20 | 120 | Ref | 116 | Ref | 94 | Ref |
GG | ≥20 | 31 | 7.98 (0.64–98.90) | 21 | 6.84 (0.76–61.89) | 19 | 0.90 (0.04–21.95) | |
TT/GT | <20 | 458 | 4.84 (0.63–37.13) | 146 | 1.74 (0.35–8.58) | 93 | 0.15 (0.01–2.10) | |
GG | <20 | 100 | 7.64 (0.88–66.52) | 44 | 7.44 (1.11–49.79) * | 26 | 1.60 (0.13–19.78) | |
Pinteraction | 0.8345 | 0.7612 | 0.3993 | |||||
VDR | ||||||||
rs10783219 | AA | ≥20 | 309 | Ref | 431 | Ref | 336 | Ref |
TA | ≥20 | 412 | 1.15 (0.44–3.05) | 523 | 0.80 (0.36–1.77) | 397 | 1.66 (0.67–4.12) | |
TT | ≥20 | 140 | 0.96 (0.24–3.87) | 156 | 0.41 (0.09–1.90) | 120 | 0.77 (0.16–3.86) | |
AA | <20 | 602 | 1.28 (0.52–3.15) | 297 | 0.78 (0.30–2.02) | 145 | 1.44 (0.41–5.02) | |
TA | <20 | 739 | 1.15 (0.47–2.78) | 419 | 1.00 (0.45–2.21) | 194 | 0.71 (0.18–2.78) | |
TT | <20 | 253 | 0.90 (0.29–2.80) | 135 | 1.04 (0.33–3.31) | 65 | 2.65 (0.66–10.67) | |
Pinteraction | 0.8452 | 0.1733 | 0.945 | |||||
rs2238136 | CC | ≥20 | 111 | Ref | 99 | Ref | 83 | Ref |
TC/TT | ≥20 | 40 | 4.94 (0.42–58.60) | 38 | 6.78 (0.84–54.44) | 30 | 0.77 (0.06–9.56) | |
CC | <20 | 363 | 5.26 (0.68–40.67) | 126 | 4.10 (0.66–25.32) | 77 | 0.44 (0.06–3.28) | |
TC/TT | <20 | 196 | 3.82 (0.45–32.40) | 65 | 2.57 (0.29–22.94) | 42 | — | |
Pinteraction | 0.4588 | 0.0586 | 0.9648 |
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Si, S.; Mo, M.; Cheng, H.; Peng, Z.; Alifu, X.; Zhou, H.; Chi, P.; Zhuang, Y.; Yu, Y. The Association of Vitamin D and Its Pathway Genes’ Polymorphisms with Hypertensive Disorders of Pregnancy: A Prospective Cohort Study. Nutrients 2022, 14, 2355. https://doi.org/10.3390/nu14112355
Si S, Mo M, Cheng H, Peng Z, Alifu X, Zhou H, Chi P, Zhuang Y, Yu Y. The Association of Vitamin D and Its Pathway Genes’ Polymorphisms with Hypertensive Disorders of Pregnancy: A Prospective Cohort Study. Nutrients. 2022; 14(11):2355. https://doi.org/10.3390/nu14112355
Chicago/Turabian StyleSi, Shuting, Minjia Mo, Haoyue Cheng, Zhicheng Peng, Xialidan Alifu, Haibo Zhou, Peihan Chi, Yan Zhuang, and Yunxian Yu. 2022. "The Association of Vitamin D and Its Pathway Genes’ Polymorphisms with Hypertensive Disorders of Pregnancy: A Prospective Cohort Study" Nutrients 14, no. 11: 2355. https://doi.org/10.3390/nu14112355
APA StyleSi, S., Mo, M., Cheng, H., Peng, Z., Alifu, X., Zhou, H., Chi, P., Zhuang, Y., & Yu, Y. (2022). The Association of Vitamin D and Its Pathway Genes’ Polymorphisms with Hypertensive Disorders of Pregnancy: A Prospective Cohort Study. Nutrients, 14(11), 2355. https://doi.org/10.3390/nu14112355