Association of VDR-gene variants with factors related to the metabolic syndrome, type 2 diabetes and vitamin D deficiency

Gene ◽  
2014 ◽  
Vol 542 (2) ◽  
pp. 129-133 ◽  
Author(s):  
Nasser M. Al-Daghri ◽  
Omar S. Al-Attas ◽  
Khalid M. Alkharfy ◽  
Nasiruddin Khan ◽  
Abdul Khader Mohammed ◽  
...  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jing Xiao ◽  
Jingyi Lv ◽  
Shiyu Wang ◽  
Yang Zhou ◽  
Lunwen Chen ◽  
...  

Abstract Background Vitamin D deficiency has been associated with type 2 diabetes (T2D) and metabolic syndrome (MS) and its components. However, it is unclear whether a low concentration of vitamin D is the cause or consequence of these health conditions. Thus, this study aimed to evaluate the association of vitamin D concentrations and its genetic risk scores (GRSs) with MS and its component diseases, such as T2D, in middle-aged and elderly participants from rural eastern China. Methods A subset of 2393 middle-aged and elderly individuals were selected from 70,458 participants of the Nantong Chronic Diseases Study of 2017–2018 in China. We used two 25-hydroxyvitamin D (25[OH]D) synthesis single-nucleotide polymorphisms (SNPs) (DHCR7-rs12785878 and CYP2R1-rs10741657) and two 25(OH) D metabolism SNPs (GC-rs2282679 and CYP24A1-rs6013897) for creating GRSs, which were used as instrumental variables to assess the effect of genetically lowered 25(OH) D concentrations on MS and T2D based on the Wald ratio. F statistics were used to validate that the four SNPs genetically determined 25(OH) D concentrations. Results Compared to vitamin D sufficient individuals, individuals with vitamin D insufficiency had an odds ratio (OR [95% confidence interval {CI}]) of MS of 1.30 (1.06–1.61) and of T2D of 1.32 (1.08–1.64), individuals with vitamin D deficiency had an ORs (95% CI) of MS of 1.50 (1.24–1.79) and of T2D of 1.47 (1.12–1.80), and those with vitamin D severe deficiency had an ORs (95% CI) of MS of 1.52 (1.29–1.85) and of T2D of 1.54 (1.27–1.85). Mendelian randomization analysis showed a 25-nmol/L decrease in genetically instrumented serum 25(OH) D concentrations using the two synthesis SNPs (DHCR7 and CYP2R1 genes) associated with the risk of T2D and abnormal diastolic blood pressure (DBP) with ORs of 1.10 (95%CI: 1.02–1.45) for T2D and 1.14 (95%CI: 1.03–1.43) for DBP. Conclusions This one sample Mendelian randomization analysis shows genetic evidence for a causal role of lower 25(OH) D concentrations in promoting of T2D and abnormal DBP in middle-aged and elderly participants from rural China.


2021 ◽  
Author(s):  
Jing Xiao ◽  
Jingyi Lv ◽  
Shiyu Wang ◽  
Yang Zhou ◽  
Lunwen Chen ◽  
...  

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.


Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2651 ◽  
Author(s):  
Uwe Gröber ◽  
Michael F. Holick

The results of epidemiological and several interventional studies suggest an association between vitamin D deficiency and an increased risk of developing insulin resistance or type 2 diabetes. Various studies have indicated that a lack of vitamin D must be regarded as a pathogenic factor for type 2 diabetes and the metabolic syndrome, since a vitamin D deficiency (25(OH)D < 20 ng/mL) increases insulin resistance and reduces insulin secretion from beta cells in the pancreas. A recent study by Pittas et al. did not show a clear preventive effect of vitamin D supplementation with respect to the risk of developing type 2 diabetes. In terms of this study, it must be remembered that more than 70% of the participants in both the vitamin D supplement group and the placebo group did not have a vitamin D deficiency. In medical and pharmaceutical practice, more attention should be paid to vitamin D deficiency than has previously been accorded. Vitamin D status can be assessed objectively when necessary by laboratory testing of the serum 25(OH)D levels. Type 2 diabetes patients benefit from improving their vitamin D status with respect to their glucose metabolism and decreased mortality risk. Patients with insulin resistance who are vitamin D deficient should be treated with an appropriate amount of vitamin D to achieve circulating levels of 25(OH)D of 40–60 ng/mL.


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