Abstract
Emerging evidence suggests a role for 7-dehydrocholesterol reductase (DHCR7) in the crosstalk between cholesterol and vitamin D. Our aim was to evaluate the impact of vitamin D-related polymorphisms and DHCR7 levels in the association between vitamin D deficiency and altered lipid profile in rheumatoid arthritis (RA). Serum 25(OH)-vitamin D, DHCR7 levels and vitamin D-related polymorphisms (VDR-rs2228570, CYP27A1-rs933994, CYP2R1-rs10741657 and DHCR7-rs12785878) were analyzed in 211 RA patients,94 controls and in a prospective cohort of 13 RA patients undergoing TNFα-blockade. Vitamin D was decreased in RA (p < 0.001), correlated to HDL-cholesterol (r = 0.217, p < 0.001) and total-/HDL-cholesterol ratio (r = −0.227, p = 0.004). These correlations were restricted to the VDR-rs2228570 status. Vitamin D deficiency was associated with lower HDL-cholesterol (p = 0.028), higher tender (p = 0.005) and swollen (p = 0.002) joint counts, higher DAS28 (p = 0.018) and HAQ (p = 0.024) in AG/AA-patients but not in their GG-counterparts. The associations among DHCR7, vitamin D and lipid profile followed a seasonal pattern, decreased DHCR7 (p = 0.008) and vitamin D (p < 0.001) and increased total-cholesterol (p = 0.025) being found in winter/spring. Increasing vitamin D upon TNFα-blockade paralleled RA clinical improvement (r = −0.610, p = 0.027) and DHCR7 elevation (r = 0.766, p = 0.002). In conclusion, vitamin D-related polymorphisms and DHCR7 are pivotal to understand the complex, seasonal associations between vitamin D and lipid profile in RA.
Highlights
In the field of rheumatic disorders, vitamin D deficiency is a common laboratory finding[4,5]
Serum 25(OH)-vitamin D levels were measured in 211 rheumatoid arthritis (RA) patients and 94 healthy controls (HC)
CYP2R1-rs10741657 and DHCR7-rs12785878 had an effect on vitamin D levels in RA patients (Supplementary Table 2)
Summary
In the field of rheumatic disorders, vitamin D deficiency is a common laboratory finding[4,5]. The circulating levels of vitamin D metabolites are influenced by several factors ranging from seasonality[10] to a number of bio-activating enzymes[11]. Www.nature.com/scientificreports polymorphisms have been described for all these genes, linked to altered serum levels of vitamin D metabolites (CYP2R1, CYP27B1, CYP24A1 and others) and actions (like those in VDR)[12]. The main aims of the present study are (i) to evaluate the associations between vitamin D levels and clinical outcomes and lipid profile in RA patients depending on their genetic status of VDR (rs2228570), CYP27A1 (rs933994), CYP2R1 (rs10741657) and DHCR7 (rs12785878) polymorphisms, (ii) to analyze the levels of DHCR7 and its associations with the lipid profile and (iii) to prospectively evaluate the effect of RA activity on the former associations in a group of patients followed-up upon Tumor Necrosis Factor alpha (TNFα)-blockade
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