Association between the rs1544410 polymorphism in the vitamin D receptor (VDR) gene and insulin secretion after gestational diabetes mellitus

Nael Shaat; Anastasia Katsarou; Bushra Shahida; Rashmi B Prasad; Karl Kristensen; Tereza Planck

doi:10.1371/journal.pone.0232297

Association between the rs1544410 polymorphism in the vitamin D receptor (VDR) gene and insulin secretion after gestational diabetes mellitus

PLoS One. 2020 May 14;15(5):e0232297. doi: 10.1371/journal.pone.0232297. eCollection 2020.

Authors

Nael Shaat^{1

2}, Anastasia Katsarou^{1

2}, Bushra Shahida¹, Rashmi B Prasad¹, Karl Kristensen^{1

3}, Tereza Planck^{1

2}

Affiliations

¹ Department of Clinical Sciences, Genomics, Diabetes and Endocrinology, Lund University, Malmö, Sweden.
² Department of Endocrinology, Skåne University Hospital, Malmö, Sweden.
³ Department of Obstetrics and Gynaecology, Skåne University Hospital, Malmö, Sweden.

Abstract

Background and aims: Genetic variants involved in vitamin D metabolism have been associated with diabetes and related syndromes/diseases. We wanted to investigate possible associations of polymorphisms in genes involved in vitamin D metabolism with indices of insulin resistance and insulin secretion, and also with development of diabetes after gestational diabetes mellitus (GDM).

Materials and methods: We have studied 376 women with previous GDM. Eight single nucleotide polymorphisms (SNPs) in the genes for vitamin D receptor (VDR) [rs731236, rs7975232, rs10735810, and rs1544410], vitamin D binding protein (DBP) [rs7041 and rs4588], and cytochrome P450 family 27 subfamily B member 1 (CYP27B1) [rs10877012 and rs4646536] were genotyped by TaqMan Allelic Discrimination Assay using the Quantstudio 7 Flex system. A 75-g oral glucose tolerance test (OGTT) was performed 1-2 years postpartum. The homeostasis model assessment of insulin resistance (HOMA-IR) and the disposition index [(insulinogenic index: I30/G30)/HOMA-IR] were used to calculate insulin resistance and insulin secretion, respectively. Serum samples for determination of 25(OH)D3 were collected at the time of the OGTT. Manifestation of diabetes was followed up to five years postpartum.

Results: After adjustment for BMI, age, and ethnicity, the A-allele of the VDR rs1544410 polymorphism was found to be associated with increased disposition index (difference per allele = 3.56, 95% CI: 0.4567-6.674; p = 0.03). The A-allele of the DBP rs7041 polymorphism was found to be associated with 25(OH)D3 levels (difference [in nmol/L] per allele = -5.478, 95% CI: -8.315 to -2.641; p = 0.0002), as was the T-allele of the DBP rs4588 polymorphism (OR = -6.319, 95% CI: -9.466 to -3.171; p = 0.0001). None of the SNPs were significantly associated with HOMA-IR or postpartum diabetes.

Conclusions: This study provides evidence that the rs1544410 polymorphism of the VDR gene may be associated with increased insulin secretion in women after pregnancy complicated by GDM. Further studies in other populations are needed to confirm the results.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Diabetes, Gestational / genetics*
Diabetes, Gestational / metabolism*
Female
Follow-Up Studies
Gene Frequency
Humans
Insulin Secretion / genetics*
Linkage Disequilibrium
Polymorphism, Single Nucleotide*
Pregnancy
Receptors, Calcitriol / genetics*

Substances

Receptors, Calcitriol
VDR protein, human

Grants and funding

The study was supported by grants from the Research Funds of Skåne University Hospital, the Skåne County Council Research and Development Foundation and ALF Region Skåne. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.