Type III hyperlipoproteinema with apolipoprotein E2/2 genotype in Japan

Area of Science:

• Cardiovascular Medicine
• Metabolic Disorders
• Genetics

Background:

• Type III hyperlipoproteinemia (HLP) is a rare genetic disorder affecting lipid metabolism.
• Limited data exists on the clinical and biochemical profile of HLP in Asian populations.
• Understanding HLP in diverse ethnicities is crucial for accurate diagnosis and management.

Purpose of the Study:

• To investigate the clinical and biochemical characteristics of type III HLP in Japanese patients.
• To compare these characteristics with those reported in Western populations.
• To assess the atherogenicity of triglyceride-rich lipoproteins in relation to diabetes.

Main Methods:

• Retrospective analysis of 16 Japanese patients diagnosed with type III HLP.
• Measurement of plasma lipid levels, including triglyceride (TG), total cholesterol (chol), and remnant-like particles (RLP)-chol.
• Assessment of associated conditions like obesity, diabetes mellitus, impaired glucose tolerance, and coronary heart disease (CHD).
• In vitro study on the effect of TG-rich lipoproteins on cholesteryl ester synthesis in human macrophages.

Main Results:

• Japanese HLP patients exhibited lower mean plasma TG (381 mg/dl) and total chol (253 mg/dl) compared to Western cohorts.
• A high prevalence of obesity (75.0%) and type 2 diabetes mellitus (43.8%) was observed.
• Coronary heart disease (CHD) was present in 37.5% of patients, with no cases of peripheral vascular disease or xanthomas.
• TG-rich lipoproteins from diabetic HLP patients significantly increased cholesteryl ester synthesis in macrophages (p < 0.001).

Conclusions:

• Japanese type III HLP patients present with distinct lipid profiles (lower TG, chol, VLDL-chol/TG ratio) but a higher prevalence of CHD.
• Obesity and glucose intolerance are common comorbidities in this population.
• Diabetic HLP patients' lipoproteins are more atherogenic, highlighting the critical role of diabetes in cardiovascular risk.