Genetic insight into putative causes of xanthelasma palpebrarum: a Mendelian randomization study

Front Immunol. 2024 Mar 27:15:1347112. doi: 10.3389/fimmu.2024.1347112. eCollection 2024.

Abstract

Xanthelasma palpebrarum (XP) is the most common form of cutaneous xanthoma, with a prevalence of 1.1%~4.4% in the population. However, the cause of XP remains largely unknown. In the present study, we used Mendelian randomization to assess the genetic association between plasma lipids, metabolic traits, and circulating protein with XP, leveraging summary statistics from large genome-wide association studies (GWAS). Genetically predicted plasma cholesterol and LDL-C, but not HDL-C or triglyceride, were significantly associated with XP. Metabolic traits, including BMI, fasting glucose, type 2 diabetes, systolic and diastolic blood pressure, were not significantly associated with XP. Furthermore, we found genetically predicted 12 circulating proteins were associated with XP, including FN1, NTM, FCN2, GOLM1, ICAM5, PDE5A, C5, CLEC11A, CXCL1, CCL2, CCL11, CCL13. In conclusion, this study identified plasma cholesterol, LDL-C, and 12 circulating proteins to be putative causal factors for XP, highlighting the role of plasma cholesterol and inflammatory response in XP development.

Keywords: Mendelian randomization; Xanthelasma palpebrarum; circulating protein; cytokine; plasma lipid.

MeSH terms

  • Cholesterol
  • Diabetes Mellitus, Type 2*
  • Genome-Wide Association Study
  • Humans
  • Membrane Proteins
  • Mendelian Randomization Analysis
  • Xanthomatosis* / epidemiology
  • Xanthomatosis* / genetics

Substances

  • Cholesterol
  • GOLM1 protein, human
  • Membrane Proteins

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by National Natural Science Foundation of China, grant number 82370490 and 32300958, Natural Science Foundation of Guangdong Province of China, grant number 2023A1515010489.