Impact of vitamin D resistance genes on vitamin D deficiency during pregnancy among the South Indian population

• Published in: Journal of reproductive immunology Vol. 160; p. 104143
• Main Authors: Milan, K.L., Jayasuriya, R., Harithpriya, K., Anuradha, M., Ramkumar, K.M.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.12.2023
• Subjects: CYP24A1; Diabetes, Gestational - epidemiology; Diabetes, Gestational - genetics; Female; Gestational diabetes mellitus; Glucose; Humans; India - epidemiology; Obstetrics and Gynecology; Oxidative stress; Pregnancy; SMRT; SNAIL; Vitamin D; Vitamin D Deficiency - epidemiology; Vitamin D Deficiency - genetics; Vitamin D3 24-Hydroxylase - genetics; Vitamins; India; Gestational diabetes mellitus; Oxidative stress; SMRT; CYP24A1; Vitamin D; SNAIL; oxidative stress
• DOI: 10.1016/j.jri.2023.104143
• ISSN: 0165-0378; 1872-7603

Increasing evidence suggests that vitamin D (Vit-D) could be pivotal in maintaining normal glucose homeostasis. Low levels of Vit-D in early pregnancy are associated with a higher risk of gestational diabetes mellitus (GDM). Though several reports have highlighted the prevalence of vit-D deficiency among pregnant women, its underlying cause has not yet been fully elucidated. In this connection, a few studies have found the development of resistance to Vit-D, including the levels of Vitamin D receptor (VDR) and transcription regulators that modify VDR action, as well as the bioavailability of Vit-D. We aimed to determine the levels of Vit-D resistance genes such as 25-HydroxyVit-D-24-hydroxylase (CYP24A1), VDR repressor genes (SNAIL and SMRT) and their association between Vit-D concentrations in early pregnancy, and the risk of gestational diabetes mellitus (GDM). A prospective observational study was conducted on healthy pregnant women (NGDM; n = 50) and GDM (n = 50) attending routine antenatal care at SRM Medical College Hospital, Chennai, recruited at 12 weeks of gestation. We found that the serum levels of Vit-D were low in GDM subjects and negatively correlated with the fasting glucose levels. Further, increased expressions of Vit-D resistance genes such as CYP24A1, SNAIL, and SMRT were observed in GDM subjects and negatively correlated with the serum levels of Vit-D. Furthermore, we have validated the data using the trophoblast cell line, BeWo, exposed to calcitriol under a hyperglycemic environment. Our finding showed that increased expression of Vit-D resistance genes in pregnancy may be associated with a greater risk of adverse pregnancy outcomes, including GDM. •Low plasma total Vit-D concentrations in early pregnancy are associated with a higher risk of gestational diabetes mellitus.•Serum levels of Vit-D were low and negatively correlated with the fasting glucose levels in GDM subjects compared to NGDM subjects.•The overexpression of Vit-D resistance genes such as CYP24A1, SNAIL, and SMRT was observed in GDM subjects and negatively correlated with the serum levels of Vit-D.•The data was validated using BeWo cell line exposed to calcitriol in a high glucose environment.