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

• Published in: PloS one 2020-05, Vol.15 (5), p.e0232297-e0232297
• Main Authors: Shaat, Nael, Katsarou, Anastasia, Shahida, Bushra, Prasad, Rashmi B, Kristensen, Karl, Planck, Tereza
• Format: Article
• Language: English
• Subjects: Alleles; Basic Medicine; Biology and Life Sciences; Body mass index; Calciferol; Cell receptors; Chromosomes; Clinical Medicine; Complications and side effects; Cytochrome; Cytochrome P-450; Cytochrome P450; Cytochromes P450; Development and progression; Diabetes; Diabetes mellitus; Endocrinology; Endocrinology and Diabetes; Endokrinologi och diabetes; Ethnicity; Gene expression; Gene polymorphism; Genes; Genetic aspects; Genetic diversity; Genetic polymorphisms; Genetic research; Genetic variance; Genomics; Gestational diabetes; Glucose; Glucose tolerance; Glucose tolerance test; Health aspects; Homeostasis; Insulin; Insulin resistance; Insulin secretion; Klinisk medicin; Medical and Health Sciences; Medical Genetics; Medicin och hälsovetenskap; Medicine and Health Sciences; Medicinsk genetik; Medicinska och farmaceutiska grundvetenskaper; Metabolic syndrome; Metabolism; Minority & ethnic groups; Nucleotides; People and Places; Physical sciences; Physiological aspects; Plasma; Polymorphism; Population studies; Postpartum; Pregnancy; Pregnant women; Protein binding; Puerperal disorders; Receptors; Regression analysis; Risk factors; Secretion; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Time; Type 2 diabetes; Vitamin D; Vitamin D receptors; Vitamin deficiency; Vitamin metabolism; Vitamins; Women; Womens health
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0232297

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). 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. 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. 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.