Association of Serum 25-Hydroxyvitamin D with Metabolic Syndrome and Type 2 Diabetes: A Mendelian Randomization Study

Abstract Background: Vitamin D deficiency is common around the world, but the association between vitamin D deficiency with metabolic syndrome and its associated diseases is unclear.Methods: A subset of 2393 participants from the Nantong Chronic Diseases Study (NCDS) of 2017-2018 were included in this study.The risk of MS and its associated diseases from low vitamin D levels were assessed by genetic scores using two 25(OH)D synthesis single nucleotide polymorphisms (SNPs) (DHCR7-rs12785878 and CYP2R1-rs10741657), one transport SNP (GC-rs2282679) and one catabolism SNP (CYP24A1-rs6013897).Results: Odds Ratios (ORs) for decreased risk of MS and type 2 diabetes (T2D) was 0.73 and 0.79 in the deficient, 0.53 and 0.67 in the insufficient, and 0.54 and 0.60 in the sufficient categories of serum vitamin D levels, respectively. Mendelian randomization analysis showed per 25nmol/L higher genetically instrumented serum 25(OH)D concentration using the two synthesis SNPs: DHCR7+CYP2R1 genes, associated with a 7% lower risk of T2D. The highest tertile vs the lowest tertile of genetic scores using the three SNPs of DHCR7+CYP2R1+GC genes showed a 10% lower risk of T2D. Also, the group with higher genetic scores among these two and three SNPs were both associated with lower risk of abnormal diastolic blood pressure (DBP) (P=0.0162 and 0.0045 respectively).Conclusions: Our Mendelian randomization analysis showed no genetic evidence for a causal role of lower vitamin D level in the development of MS, but showed a causal role in the development of T2D and DBP in middle-aged and elderly participants from rural China.