The role of vitamin D receptor gene polymorphisms in gestational diabetes mellitus susceptibility: a meta-analysis

Abstract

Background: Gestational diabetes mellitus (GDM) is a common disease during pregnancy. The association of vitamin D receptor (VDR) polymorphisms with GDM is still controversial. This study aimed to assess the associations between VDR polymorphisms and GDM risk.

Methods: We searched Cochrane Library, PubMed, and Embase electronic database for all eligible studies published from Jan 1, 1980 to December 31, 2020 to conduct a Meta-analysis. We analyzed four VDR polymorphisms: BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236), and FokI (rs2228570).

Inclusion criteria: (1) The data can be evaluated; (2) case-control study; and (3) meeting the Hardy-Weinberg's law.

Exclusion criteria: (1) Insufficient or extractable data; (2) Severe publication bias in the data; and (3) duplicate publications. We eventually included 15 studies in seven articles, including 2207 cases and 2706 controls.

Results: We eventually included 15 studies in seven articles, including 2207 cases and 2706 controls. The data showed that ApaI (rs7975232) VDR gene polymorphism was related with the risk of GDM for the comparison of CC vs AA and recessive model in overall population and FokI (rs2228570) VDR gene polymorphism was associated with the risk of GDM for recessive model in overall population. BsmI (rs1544410) polymorphism was not related with the risk of GDM in overall population. However, in the analysis of subgroups grouped by race, BsmI (rs1544410) has certain correlations. And, the data suggested the TaqI (rs731236) polymorphism was not associated with GDM.

Conclusion: Based on the meta-analysis, VDR ApaI (rs7975232) and FokI (rs2228570) polymorphisms increase susceptibility to GDM. In the future, it can be used to diagnose and screen molecular biomarkers for GDM patients.

Keywords: GDM; Gestational diabetes mellitus; Meta-analysis; VDR; Vitamin D receptor.

Fig. 1

Flow diagram detailing procedures of selecting eligible studies

Fig. 2

The funnel plot compared with the allele model for a ApaI (C vs A), b FokI (T vs C) and c BsmI (G vs A) gene polymorphisms to show publication bias

Fig. 3

Fixed-effects meta-analysis on GDM risk and VDR ApaI (rs7975232) polymorphism in overall, Asian and Caucasian population (CC versus AA)

Fig. 4

Fixed-effects meta-analysis on GDM risk and VDR ApaI (rs7975232) polymorphism under recessive model in overall and Asian population (CC vs AA + CA)

Fig. 5

Fixed-effects meta-analysis on GDM risk and VDR FokI (rs2228570) polymorphism under recessive model in overall and Caucasian population (TT vs CC + CT)

Fig. 6

Random-effects meta-analysis on GDM risk and VDR FokI (rs2228570) polymorphism under allelic model in Caucasian population (T vs C)

Fig. 7

Random-effects meta-analysis on GDM risk and VDR BsmI (rs1544410) polymorphism under dominant model in Asian and African population (GA + GG vs AA)

Fig. 8

Random-effects meta-analysis on GDM risk and VDR BsmI (rs1544410) polymorphism under over-dominant model in Asian and African population (GA vs AA + GG)