Aim: Lipoprotein lipase (LPL) deficiency is a rare autosomal recessive disorder characterized by severe hypertriglyceridemia. Similar clinical phenotypes have been reported with respect to defects in several LPL-associated proteins. However, it remains controversial whether severe hypertriglyceridemia itself is atherogenic. We herein present a case of LPL deficiency due to novel combined mutations of glycosylphosphatidylinositol (GPI)-anchored high-density lipoprotein (HDL)-binding protein 1 (GPIHBP1) in a patient with coronary artery disease (CAD).
Patient: We evaluated a 54-year-old woman with severe hypertriglyceridemia and double vessel CAD. Although the LPL mass and activity in the postheparin plasma were extremely low, no mutations were detected in the LPL gene itself.
Results: Genetic analyses revealed that the patient had double homozygous mutations at 41 bp (c.41 G > T) and 202 bp (c.202 T > C) in the GPIHBP1 gene, resulting in C14F and C68R, respectively. Although the C14F/C68R GPIHBP1 exhibited a normal LPL-binding activity, the levels of mutant proteins were extremely reduced compared to those of the wild-type proteins in vitro.
Conclusion: We found novel combined mutations of GPIHBP1 in a patient with hypertriglyceridemia and severe CAD. The present case provides important insight into the pathogenesis of severe hypertriglyceridemia associated with atherosclerosis.