The CYP24A1 Gene Variant rs2762943 Is Associated With Low Serum 1,25- Dihydroxyvitamin D Levels In Multiple Sclerosis Patients

Background: Vitamin D is considered to play a role in multiple sclerosis (MS) etiopathogenesis. We recently identified a polymorphism located in the cytochrome P450 family 24 subfamily A member 1 (CYP24A1) gene, rs2762943, that was found to be associated with an increased risk for MS. CYP24A1 codes for a protein that is involved in the catabolism of the active form of vitamin D. Here, we investigated the immunological effects of carrying the risk allele for the rs2762943 polymorphism, as well as its role as genetic modifier in MS patients. Methods: Serum levels of 25‐hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured in a cohort of 167 MS patients. In a subgroup of these patients, expression levels of MHC class II and co-stimulatory molecules were determined by flow cytometry in blood cell populations, and the levels of proinflammatory (IFNG, GM-CSF, CXCL13) and anti-inflammatory (IL-10) cytokines and neurofilament light chain were measured by single-molecule array assays in serum samples. The effect of the rs2762943 polymorphism on disease activity and disability progression measures was evaluated in a cohort of 340 MS patients. Results: Compared to non-carriers, MS patients carrying the risk allele for rs2762943 were characterized by reduced levels of 1,25(OH)2D (p=0.0001), and elevated levels of IFNG (p=0.03) and GM-CSF (p=0.008), whereas no significant differences were observed between risk allele carriers and non-carriers groups for the other evaluated markers. The presence of the risk allele for rs2762943 had no significant impact on the annualized relapse rate, EDSS and MSSS measures during follow-up. However, risk allele carriers were younger at disease onset (p=0.04). Discussion: These findings suggest that the CYP24A1 rs2762943 gene variant plays a more important role on MS susceptibility than on disease prognosis, and is associated with lower 1,25(OH)2D levels and heightened pro-inflammatory environment in MS patients.

The interaction effect of aerobic exercise and vitamin D supplementation on inflammatory factors, anti-inflammatory proteins, and lung function in male smokers: a randomized controlled trial

Background This study aimed to investigate the interaction effect of aerobic exercise and vitamin D supplementation on inflammation (TNF-α, IL-6, CC16, SP-D, and CC16/SP-D ratio) and lung function (FEV1, FVC, and FEV1/FVC ratio) in male smokers. Methods After applying inclusion criteria, a total of 40 healthy male smokers were recruited in this study. The participants were randomly divided into four groups as follows: Aerobic Exercise + vitamin D Supplementation (AE + VitD, n = 10), Aerobic Exercise (AE, n = 10), vitamin D Supplementation (VitD, n = 10), and Control (C, n = 10). The participants in the AE + VitD and AE groups performed aerobic exercise training (running) up to 50% of the maximum heart rate, three times a week for four weeks. Participants in AE + VitD and VitD groups received 6000 IU/w vitamin D3 for four weeks. The participants in control group did not receive any intervention. Serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, Clara cell protein (CC16), surfactant protein (SP)-D, CC16/SP-D ratio, and lung function (FEV1, FVC, and FEV1/FVC ratio) were measured before and after four weeks of intervention. Results Serum levels of TNF-α, IL-6, and CC16 decreased significantly in AE + VitD, VitD, and AE groups after four weeks (P < 0.05). Serum SP-D level decreased significantly only in the AE + VitD group (P = 0.011). In addition, FEV1 and FVC increased significantly (P < 0.05) in AE + VitD and AE groups after four weeks of intervention. However, the interventions did not have a significant effect on CC16/SP-D ratio and FEV1/FVC ratio (P > 0.05). Furthermore, serum levels of 1,25-dihydroxyvitamin D increased significantly in AE + VitD and VitD groups (P < 0.05) after four weeks of intervention. However, except for TNF-α, between-group comparisons showed no significant differences in levels of IL-6, CC16, SP-D, CC16/SP-D ratio, FEV1, FVC, FEV1/FVC, and 1,25-dihydroxyvitamin D (P > 0.05). Conclusions The results of present study were that aerobic exercise combined with vitamin D supplementation can reduce serum inflammatory factors and anti-inflammatory proteins and improve lung function after four weeks of intervention. Further trials with larger sample size and longer duration are suggested to confirm these results. Trial registration Retrospectively registered. IRCT20180513039637N4. Registration date: 2020/10/20. URL: https://www.irct.ir/search/result?query=IRCT20180513039637N4