Vitamin D pathway-related gene polymorphisms and their association with metabolic diseases: A literature review

Abstract

Purpose Given that the relationship between vitamin D status and metabolic diseases such as obesity and type 2 diabetes (T2D) remains unclear, this review will focus on the genetic associations, which are less prone to confounding, between vitamin D-related single nucleotide polymorphisms (SNPs) and metabolic diseases. Methods A literature search of relevant articles was performed on PubMed up to December 2019. Those articles that had examined the association of vitamin D-related SNPs with obesity and/or T2D were included. Two reviewers independently evaluated the eligibility for the inclusion criteria and extracted the data. In total, 73 articles were included in this review. Results There is a lack of research focusing on the association of vitamin D synthesis-related genes with obesity and T2D; however, the limited available research, although inconsistent, is suggestive of a protective effect on T2D risk. While there are several studies that investigated the vitamin D metabolism-related SNPs, the research focusing on vitamin D activation, catabolism and transport genes is limited. Studies on CYP27B1, CYP24A1 and GC genes demonstrated a lack of association with obesity and T2D in Europeans; however, significant associations with T2D were found in South Asians. VDR gene SNPs have been extensively researched; in particular, the focus has been mainly on BsmI (rs1544410), TaqI (rs731236), ApaI (rs7975232) and FokI (rs2228570) SNPs. Even though the association between VDR SNPs and metabolic diseases remain inconsistent, some positive associations showing potential effects on obesity and T2D in specific ethnic groups were identified. Conclusions Overall, this literature review suggests that ethnic-specific genetic associations are involved. Further research utilizing large studies is necessary to better understand these ethnic-specific genetic associations between vitamin D deficiency and metabolic diseases.

Interaction between Vitamin D-Related Genetic Risk Score and Carbohydrate Intake on Body Fat Composition: A Study in Southeast Asian Minangkabau Women

“…Low 25(OH)D concentrations have been shown to be associated with metabolic diseases, such as obesity and type 2 diabetes (T2D) [ 1 ]. Hereditary factors play a large role in VDD affecting up to 85% of serum concentrations of 25(OH)D [ 2 , 3 ] and the development of metabolic disorders [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. However, we cannot overlook the effect of environment, lifestyle, nutrition, and dietary factors as major contributors to metabolic diseases [ 13 , 14 ].…”

Rare Variants in Autophagy and Non-Autophagy Genes in Late-Onset Pompe Disease: Suggestions of Their Disease-Modifying Role in Two Italian Families

“…Considering that the insufficiency/deficiency of vitamin D is the most important biochemical/clinical biomarker identified in our families, we investigated the allelic contribution in our patients of variants associated with low levels of vitamin D in genes involved in its metabolism. As reported in Table 6 , we found in the two families an excess of CC alleles for the two variants rs2228570 (Vitamin D receptor ( VDR ) gene, c.T2C (p.M1T), also known as the FokI variant) and rs4588 (Vitamin D-binding protein ( GC/DBP ), c.C1307A (p.T436K)), which were reported as associated with low vitamin D levels in several populations [ 29 ].…”

The Role of Apa-I Vitamin D Receptor Gene Polymorphism in Type 2 Diabetes Mellitus

“…The other previous study showed that the genotypes and alleles of Apa-I Vitamin D receptor gene polymorphism are not associated with risk of T2DM in the population of Pakistan [17]. An earlier literature review study showed that of 15 studies, none of which showed a significant association between the Apa-I Vitamin D receptor gene polymorphism and the risk of T2DM (n = 171-4563), as well as the two other meta-analyzes that analyzed the risk of T2DM in 3871 individuals [18], [19], [20]. Susceptibility to suffer from T2DM is related with changes in the ability of Vitamin D receptors to bind to 1,25(OH)D. Polymorphism of the Apa-I Vitamin D receptor alters the activity and affinity of this receptor binding to 1,25(OH)D. Changes in activity and affinity of Vitamin D receptors will be changed circulating of 1,25(OH)D which, in turn, affects sensitivity and resistance of insulin [10], [21].…”