Background/Purpose: Vitamin D deficiency is a common hallmark of rheumatic diseases, and some controversy exists about its effect on rheumatoid arthritis (RA), in particular about the association between vitamin D levels and lipid profiles. Several factors influence this cross-talk, including polymorphisms in vitamin D bioactivating enzymes (CYP27A1 and CYP2R1) and signaling (vitamin D receptor), and 7-dehydrocholesterol reductase (7DHCR7), an enzyme using a common metabolite to vitamin D and cholesterol syntheses. The contribution of these factors to the association between vitamin D and lipid profiles in RA is unknown. The main aim of this study was to evaluate the impact of vitamin D-related polymorphisms and DHCR7 serum levels on the association between vitamin D and lipid profile in RA.

Methods: Serum 25(OH)-vitamin D and DHCR7 levels were measured in a cross-sectional group of 211 RA patients (EULAR/ACR 2010 criteria) and 94 healthy controls (HC). An additional group of 13 RA patients undergoing anti-TNFa treatment was prospectively followed for 3 months and samples were taken before and after TNFα-blockade. VDR-rs2228570, CYP27A1-rs933994, CYP2R1-rs10741657 and DHCR7-rs12785878 polymorphisms were genotyped with TaqMan Assays.

Results: RA patients exhibited decreased vitamin D levels (p<0.001), but no associations with disease activity, duration, HAQ or treatments were found. Vitamin D levels were correlated with HDL-cholesterol (r=0.217, p<0.001) and total-/HDL-cholesterol ratio (r=-0.227, p=0.004). This correlation was restricted to patients harboring the VDR-rs2228570 AG/AA genotype, and vitamin D levels remained the only predictor of HDL-cholesterol in these patients in a multivariate regression analysis adjusted for age, gender, seasonality, disease activity and treatments (B[95% CI], p: 0.246 [0.036, 0.455], p=0.022). Vitamin D deficiency (<20 ng/ml) 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 (all p>0.050). No differences in the distribution of any of the polymorphisms was found between patients and controls none of them showed any effect on HDL-cholesterol. On the other hand, decreased DHCR7 serum levels were observed in RA compared to HC in individuals sampled in winter/spring (p=0.012) but not in summer/autumn (p=0.354). RA patients with a previous history of CV disease exhibited decreased DHCR7 levels than their CV-free counterparts (p=0.024). The associations among DHCR7, vitamin D and lipid profile followed a seasonal pattern, decreased DHCR7 (p=0.008) and vitamin D (p<0.001) together with increased total-cholesterol (p=0.025) being found in winter/spring. Finally, increasing vitamin D upon TNFα-blockade was positively correlated to the change in DHCR7 levels (r=0.766, p=0.002).

Conclusion: The adverse impact of vitamin D deficiency on the lipid profile and clinical features in RA is influenced by the VDR-rs2228570 polymorphism and DHCR7 levels. DHCR7 may be a missing link to better understand the connections between vitamin D, lipid profiles and seasonality in RA.

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-association-of-vitamin-d-with-the-lipid-profile-in-rheumatoid-arthritis-an-interplay-among-genetic-polymorphisms-dhcr7-levels-and-seasonality/