Mendelian Randomization Study on hs-CRP and Dyslipidemia in Koreans: Identification of Novel SNP rs76400217

Int J Mol Sci. 2025 Jan 9;26(2):506. doi: 10.3390/ijms26020506.

Abstract

High-sensitivity C-reactive protein (hs-CRP) is a marker of systemic inflammation and is associated with developing dyslipidemia. However, the causality between hs-CRP and dyslipidemia remains unresolved. This study aimed to investigate the relationship between hs-CRP concentrations and dyslipidemia and to explore the potential causal link using Mendelian randomization (MR) analysis. A nested case-control study was conducted with 1174 participants, and genotype data were analyzed using the Korean Chip. A genome-wide association study (GWAS) identified rs76400217 as a suitable instrumental variable (IV) due to its significant association with hs-CRP (p < 10-8). Logistic regression models, adjusted for confounders, were used to evaluate the association between hs-CRP and dyslipidemia. An MR analysis was performed using a two-stage least squares (2SLS) method, with rs76400217 as the IV to assess causality. Logistic regression showed a significant association between hs-CRP concentrations and dyslipidemia (OR 2.08, 95% CI: 1.81-2.39, p < 0.001). This association remained significant after adjusting for factors such as age, sex, alcohol consumption, and BMI. The MR analysis using rs76400217 as the IV confirmed the strong associations with hs-CRP concentrations (p < 0.001) in all models, but the causality between hs-CRP and dyslipidemia was not statistically significant. Thus, no evidence of a causal relationship between hs-CRP and the risk of dyslipidemia was found in the Korean population. The strong association observed between hs-CRP and dyslipidemia may be due to other contributing factors rather than a direct cause.

Keywords: Mendelian randomization; causal relationship; dyslipidemia; high-sensitivity C-reactive protein.

MeSH terms

  • Adult
  • Aged
  • Asian People / genetics
  • C-Reactive Protein* / analysis
  • C-Reactive Protein* / genetics
  • C-Reactive Protein* / metabolism
  • Case-Control Studies
  • Dyslipidemias* / blood
  • Dyslipidemias* / epidemiology
  • Dyslipidemias* / genetics
  • East Asian People
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Mendelian Randomization Analysis*
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Republic of Korea / epidemiology

Substances

  • C-Reactive Protein