Impact of novel causal gene mutation of familial hypercholesterolemia on its clinical features and prognosis

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591041
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kanazawa University
• Principal Investigator: KAWASHIRI MASAAKI 金沢大学, 医学系, 准教授 (90345637)
• Co-Investigator(Kenkyū-buntansha): NOGUCHI Tohru 金沢大学, 医学系, 助教 (40456421)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 家族性高コレステロール血症 / PCSK9 / LDLコレステロール

Outline of Final Research Achievements

A gain-of-function mutation of proprotein convertase subtilisin/kexin type9 (PCSK9) gene results in familial hypercholesterolemia (FH) through degeneration of hepatic low-density lipoprotein (LDL) receptor. PCSK9 E32K is considered as gain-of-function mutation because HepG2 cells transient transfected PCSK9 E32K plasmid secretes 139% of PCSK9 protein compared with wild type. We found 9 patient with double heterozygous of LDL receptor gene mutation and PCSK9 E32K mutation, and their LDL-cholesterol levels ranged from 195 to 581 mg/dL. The most severe case was accompanied with large tendon xanthoma resembling homozygous FH as well as extreme hypercholesterolemia. These findings suggest that some additive hereditary factors are needed to exacerbate clinical features of PCSK9 E32K carriers.

Free Research Field

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