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

Buthaina E Alathari; Aji A Sabta; Chinnappan A Kalpana; Karani Santhanakrishnan Vimaleswaran

doi:10.1007/s40200-020-00561-w

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

J Diabetes Metab Disord. 2020 Jun 16;19(2):1701-1729. doi: 10.1007/s40200-020-00561-w. eCollection 2020 Dec.

Authors

Buthaina E Alathari^{1

2}, Aji A Sabta^{3

4}, Chinnappan A Kalpana⁵, Karani Santhanakrishnan Vimaleswaran¹

Affiliations

¹ Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, PO Box 226, Whiteknights, Reading, RG6 6AP UK.
² Department of Food Science and Nutrition, Faculty of Health Sciences, The Public Authority for Applied Education and Training, P.O. Box 14281, AlFaiha , 72853 Kuwait.
³ Department of Nutrition, Faculty of Health Sciences, University Alma Ata, Yogyakarta, 55183 Indonesia.
⁴ Postgraduate Biomedical Science Department, Faculty of Medicine, Andalas University, West Sumatra , 25172 Indonesia.
⁵ Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore, Tamil Nadu India.

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.

Keywords: 25(OH)D; Genetics of vitamin D; Obesity; SNPs; Type 2 diabetes; Vitamin D.

Publication types

Review

Grants and funding

MR/S024778/1/MRC_/Medical Research Council/United Kingdom