Lipids, lipid-lowering drugs and lateral epicondylitis of the humerus: a drug-targeted Mendelian randomization study

TL;DR

This study uses genetic data to investigate if blood lipids or lipid-lowering drugs affect the risk of lateral epicondylitis, finding that only lipoprotein lipase shows a protective effect.

Contribution

The study identifies lipoprotein lipase as a potential drug target for lateral epicondylitis using Mendelian randomization and colocalization analysis.

Findings

No correlation was found between LDL-C, triglycerides, or total cholesterol and lateral epicondylitis.

Lipoprotein lipase (LPL) enhancement is significantly associated with a decreased risk of lateral epicondylitis.

LPL expression shares a single causal variant with lateral epicondylitis, with a high colocalization probability.

Abstract

Clinical observations indicate that blood lipids may be risk factors for lateral epicondylitis (LE) of the humerus, and lipid-lowering drugs are also used for the prevention and treatment of tendon diseases, but these lack high-quality clinical trial evidence and remain inconclusive. Mendelian randomization (MR) analyses can overcome biases in traditional observational studies and offer more accurate inference of causal relationships. Therefore, we employed this approach to investigate whether blood lipids are risk factors for LE and if lipid-lowering drugs can prevent it.

Genetic variations associated with lipid traits, including low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and total cholesterol (TC), were obtained from the UK Biobank and the Global Lipids Genetics Consortium (GLGC). Data on genetic variation in LE were sourced from FinnGen, including 24,061 patients and 275,212 controls. Subsequently, MR analyses were conducted to assess the potential correlation between lipid traits and LE. Additionally, drug-target Mendelian randomization analyses were performed on 10 drug targets relevant to LE. For those drug targets that yielded significant results, further analysis was conducted using colocalization techniques.

No correlation was found between three blood lipid traits and LE. Lipoprotein lipase (LPL) enhancement is significantly associated with a decreased risk of LE (OR = 0.76, [95% CI, 0.65–0.90], p = 0.001). The expression of LPL in the blood is associated with LE and shares a single causal variant (12.07%), greatly exceeding the probability of different causal variations (1.93%), with a colocalization probability of 86.2%.

The three lipid traits are not risk factors for lateral epicondylitis. LPL is a potential drug target for the prevention and treatment of LE.

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