The effect of CYP2R1 polymorphism (rs10741657) on serum lipid traits in a Han septic population: A case-control study

Vitamin D deficiency has been proven to be associated with dyslipidemia. Additionally, the synthesis of vitamin D depends on cytochrome P450 2R1 (CYP2R1). However, the relationship between CYP2R1 polymorphisms and lipid metabolism has shown inconsistent results. A case-control study was conducted in a Han Chinese population, including 92 septic patients and 92 polytrauma patients. Based on serum lipid levels, 28 septic patients were further divided into a hyperlipidemia group, while 64 were placed in the control group; similarly, 34 polytrauma patients were categorized into a hyperlipidemia group and 58 into the control group. Genotyping of CYP2R1-rs10741657 was performed and serum lipid levels were measured. The Genotype-Tissue Expression project was used to assess expression quantitative trait loci for CYP2R1 mRNA expression and rs10741657. The genetic analyses revealed that the G-allele of CYP2R1-rs10741657 was significantly associated with an increased risk of hyperlipidemia in both sepsis (OR = 2.333, 95% CI: 1.227-4.436, P = .010) and polytrauma groups (OR = 4.000, 95% CI: 2.048-7.811, P < .001). Further analysis indicated that the rs10741657 mutation was mainly linked to higher serum high-density lipoprotein cholesterol levels in controls (P < .05). In functional analysis of rs10741657, the mutation was found to be associated with high CYP2R1 mRNA expression in whole blood from expression quantitative trait loci data (P = 3.53 × 10-9). In conclusion, the G-allele of CYP2R1-rs10741657 could elevate high-density lipoprotein cholesterol levels and protect against sepsis development.