Abstract
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.
Highlights
Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy [1]
After adjustment for body mass index (BMI), age, and ethnicity, the A-allele of the vitamin D receptor (VDR) rs1544410 polymorphism was found to be associated with increased disposition index
The A-allele of the D binding protein gene (DBP) rs7041 polymorphism was found to be associated with 25(OH)D3 levels, as was the T-allele of the DBP rs4588 polymorphism
Summary
Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy [1]. The mechanisms may be mediated by activation of the vitamin D receptor (VDR) on pancreatic beta cells and insulin-sensitive organs and by regulation of calcium homeostasis [7, 8]. Studies have suggested that circulating concentrations of vitamin D may be inversely associated with the risk of diabetes, metabolic syndrome, insulin secretion, and insulin resistance [8,9,10]. In addition to a meta-analysis, have found associations between polymorphisms in the VDR gene and both diabetes and insulin resistance-related diseases [11, 12]. Single nucleotide polymorphisms (SNPs) in the vitamin D binding protein gene (DBP) affect 25 (OH)D3 levels [13, 14] and increase the risk of T2D and the metabolic syndrome [15, 16]. There is evidence of associations between polymorphisms in the CYP27B1 gene and type-1 diabetes [17, 18]
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