[No authors listed]
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 (pâ<â0.001), correlated to HDL-cholesterol (râ=â0.217, pâ<â0.001) and total-/HDL-cholesterol ratio (râ=â-0.227, pâ=â0.004). These correlations were restricted to the VDR-rs2228570 status. Vitamin D deficiency was associated with lower HDL-cholesterol (pâ=â0.028), higher tender (pâ=â0.005) and swollen (pâ=â0.002) joint counts, higher DAS28 (pâ=â0.018) and HAQ (pâ=â0.024) 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 (pâ=â0.008) and vitamin D (pâ<â0.001) and increased total-cholesterol (pâ=â0.025) being found in winter/spring. Increasing vitamin D upon TNFα-blockade paralleled RA clinical improvement (râ=â-0.610, pâ=â0.027) and DHCR7 elevation (râ=â0.766, pâ=â0.002). In conclusion, vitamin D-related polymorphisms and DHCR7 are pivotal to understand the complex, seasonal associations between vitamin D and lipid profile in RA.
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