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Background rheumatoid arthritis (RA) is associated with increased cardiovascular (CV) risk. Although vitamin D deficiency has been linked to CV disease in other conditions, studies in RA have yielded contradictory results and pointed to the involvement of additional factors. On the one hand, several genetic polymorphisms have been linked to vitamin D levels. Moreover, emerging evidence suggests a role for the enzyme DHCR7 in the crosstalk between cholesterol and vitamin D synthesis. Objectives to evaluate the effect of genetic polymorphisms and DHCR7 levels in the interaction between vitamin D and lipid profile in RA. Methods serum levels of vitamin D and DHCR7 were measured in 212 RA patients (2010 EULAR/ACR criteria) and 104 matched healthy controls (HC) by chemiluminescence and immunoassays, respectively. VDR rs2228750 and DHCR7 rs12785878 SNPs were studied by TaqMan Assays. The effect of vitamin D deficiency on clinical features was assessed by linear regression analyses adjusting for age, gender, seasonality, vitamin D supplementation and DMARD usage. Results decreased vitamin D was found in RA compared to HC (p 0.050). Decreased DHCR7 levels were found between RA and HC in winter/spring (p=0.008) but not in summer/autumn (p=0.116). RA patients with CV disease exhibited lower DHCR7 levels (p=0.012) than their CV-free counterparts. Moreover, the associations among DHCR7, vitamin D and HDL levels followed a seasonal pattern: DHCR7 was correlated to vitamin D levels in summer/autumn (r=0.441, p=0.004), where vitamin D was associated with both HDL levels (r=0.354, p=0.009) and total/HDL ratio (r=−0.393, p=0.003). A DHCR7 rs12785878-driven effect was observed for these associations. On the contrary, a weak correlation between HDL and vitamin D was found in winter/spring (r=0.215, p=0.014), where decreased DHCR7 was associated with age at onset (r=−0.285, p=0.006) and RF titre (r=−0.326, p=0.013). Conclusions the effect of vitamin D on the lipid profile is dependent on genetic polymorphisms. DHCR7 has a pivotal role in the interaction between vitamin D and lipid profile in RA. Seasonality and DHCR7-HDL axis may be novel mediators in the CV disease in RA. Disclosure of Interest None declared