Cholesterol and low-density lipoprotein as a cause of psoriasis: Results from bidirectional Mendelian randomization

J Eur Acad Dermatol Venereol. 2024 Apr;38(4):710-718. doi: 10.1111/jdv.19670. Epub 2023 Nov 29.

Abstract

Background: Psoriasis is an inflammatory disease that affects many people. However, the causal effect of lipid metabolism on psoriasis has not yet been verified. This study aimed to identify the genetic relationship between serum lipid levels and psoriasis.

Methods: Bidirectional two-sample Mendelian randomization (MR) was used to analyse the causal relationship between cholesterol and psoriasis. The outcome of the forward causality test was psoriasis. In the analysis of reverse causality, psoriasis was exposed, and 79 single-nucleotide polymorphisms were detected in the genome-wide association study (GWASs) database from the IEU GWASs Project. MR-Egger regression, inverse variance-weighted, weighted median, weighted mode and simple mode were used for the MR analyses.

Results: The level of triglyceride, lipase member N, chylomicrons, extremely large very low-density lipoprotein (VLDL) particles, high-density lipoprotein (HDL) cholesterol levels, cholesterol esters in large HDL, cholesterol esters in medium HDL and cholesterol esters in medium VLDL have not affected the development of psoriasis. However, total cholesterol, total free cholesterol, low-density lipoprotein (LDL) cholesterol levels, cholesterol esters in large VLDL and cholesterol esters in medium LDL were unidirectional causal effects on psoriasis.

Conclusion: Bidirectional two-sample MR analysis indicated that high levels of total cholesterol, total free cholesterol, LDL cholesterol, cholesterol esters in large VLDL and cholesterol esters in medium LDL are genetic risk factors for psoriasis.

MeSH terms

  • Cholesterol
  • Cholesterol Esters*
  • Cholesterol, HDL / genetics
  • Cholesterol, LDL
  • Genome-Wide Association Study
  • Humans
  • Mendelian Randomization Analysis*
  • Polymorphism, Single Nucleotide
  • Triglycerides / genetics

Substances

  • Cholesterol Esters
  • Cholesterol, HDL
  • Cholesterol
  • Triglycerides
  • Cholesterol, LDL