Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2023 Apr 25:11:e15181.
doi: 10.7717/peerj.15181. eCollection 2023.

Association between Vitamin D receptor (VDR) gene polymorphisms and hypertensive disorders of pregnancy: a systematic review and meta-analysis

Yicong Guo #  1 , Yu Zhang #  2 , Xiangling Tang  2 , Xionghao Liu  2 , Huilan Xu  1
Affiliations
Meta-Analysis

Association between Vitamin D receptor (VDR) gene polymorphisms and hypertensive disorders of pregnancy: a systematic review and meta-analysis

Yicong Guo et al. PeerJ. .

Abstract

Background: Hypertensive disorders of pregnancy (HDP) are currently one of the major causes of pregnancy-related maternal and fetal morbidity and mortality worldwide. Recent studies provide evidence that maternal Vitamin D receptor (VDR) gene polymorphisms probably play a key role by affecting the biological function of vitamin D in some adverse pregnancy outcomes, while the relationship between the VDR gene polymorphisms and the risk of HDP remains controversial in current studies. This systematic review and meta-analysis aimed to comprehensively evaluate the association of the VDR gene polymorphisms with HDP susceptibility.

Methods: This meta-analysis follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and a protocol has been registered in the PROSPERO (ID: CRD42022344383) before commencing this review. PubMed, Web of Science, Embase, and the Cochrane Library databases were searched until January 21, 2023. Case-control and cohort studies that reported the association of the VDR gene polymorphisms with HDP were included. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS) for non-randomized studies. The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) of the five models (allele model, dominant model, recessive model, homozygous model, heterozygous model) were pooled respectively, and subgroup analysis was performed based on ethnicity.

Results: A total of ten studies were included. The VDR gene ApaI polymorphism was associated with HDP susceptibility in the dominant model (OR: 1.38; 95% CI [1.07-1.79]; P = 0.014) and the heterozygote model (OR: 1.48; 95% CI [1.12-1.95]; P = 0.006). In subgroup analysis, the heterozygote model (OR: 2.06; 95% CI [1.21-3.52]; P = 0.008) of the ApaI polymorphism was associated with HDP in Asians, but not in Caucasians.

Conclusion: The VDR gene ApaI polymorphism may be associated with HDP susceptibility. Insufficient evidence to support the existence of ethnic differences in this association.

Keywords: Gestational hypertension; Hypertensive disorders of pregnancy; Meta-analysis; Polymorphisms; Preeclampsia; Systematic review; Vitamin D receptor.

PubMed Disclaimer

Conflict of interest statement

The authors declare there are no competing interests.

Figures

Figure 1
Figure 1. Flow chart of the included studies of meta-analysis.
Figure 2
Figure 2. Forest plot for pooled odds ratio (OR) and the corresponding 95% confidence interval (CI) of the association between the ApaI polymorphism and hypertensive disorders of pregnancy (HDP).
(A) Dominant model (aa + Aa vs. AA); (B) heterozygote model (Aa vs. AA).
Figure 3
Figure 3. Forest plot for pooled odds ratio (OR) and the corresponding 95% confidence interval (CI) of the association between the BsmI polymorphism and hypertensive disorders of pregnancy (HDP) in the homozygote model (bb vs. BB).
Figure 4
Figure 4. Forest plot for pooled odds ratio (OR) and the corresponding 95% confidence interval (CI) of the association between the FokI polymorphism and hypertensive disorders of pregnancy (HDP).
(A) Recessive model (ff + Ff vs. FF) in Caucasians; (B) Recessive model (ff vs. Ff + FF) in the overall population.
Figure 5
Figure 5. Sensitivity analysis of the studies included for the ApaI polymorphism; (A) Dominant model (aa + Aa vs. AA); (B) heterozygote model (Aa vs. AA).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Alpoim PN, Gomes KB, Pinheiro Mde B, Godoi LC, Jardim LL, Muniz LG, Sandrim VC, Fernandes AP, Dusse LM. Polymorphisms in endothelial nitric oxide synthase gene in early and late severe preeclampsia. Nitric Oxide. 2014;42:19–23. doi: 10.1016/j.niox.2014.07.006. - DOI - PubMed
    1. Antza C, Cifkova R, Kotsis V. Hypertensive complications of pregnancy: a clinical overview. Metabolism: Clinical and Experimental. 2018;86:102–111. doi: 10.1016/j.metabol.2017.11.011. - DOI - PubMed
    1. Aziz A, Shah M, Siraj S, Iqbal W, Jan A, Khan I, Ahmed S, Vitale SG, Angioni S. Association of vitamin D deficiency and vitamin D receptor (VDR) gene single-nucleotide polymorphism (rs7975232) with risk of preeclampsia. Gynecological Endocrinology. 2022;39(1):2146089. doi: 10.1080/09513590.2022.2146089. - DOI - PubMed
    1. Bartsch E, Medcalf KE, Park AL, Ray JG. Clinical risk factors for pre-eclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies. Bmj. 2016;353:i1753. doi: 10.1136/bmj.i1753. - DOI - PMC - PubMed
    1. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–1101. doi: 10.2307/2533446. - DOI - PubMed