Mouse anti-Human FH polyclonal antibody

Ultrasound-guided measurement of carotid intima-media thickness can be used as a surrogate marker to predict future risk of atherosclerotic cardiovascular disease, and to understand the efficacy of lipid-lowering drugs. Aggressive lipid-lowering drugs such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to reduce carotid artery plaque burden, total cholesterol, and low-density lipoprotein-c in patients with heterozygous familial hypercholesterolemia (FH). We describe a patient with heterozygous FH treated with PCSK9 inhibitor over the course of two years, and the drug's impact on carotid intima-media thickness, Achilles tendon thickness, and cardiovascular disease risk reduction.

BACKGROUND: Little data exist on the pathogenic mutations of LDL receptor in Japanese familial hypercholesterolemia (FH). OBJECTIVE: We aimed to catalog the pathogenic mutations of LDL receptor gene in the 2 major Japanese FH-care centers (Kanazawa University and National Cerebral and Cardiovascular Center Research Institute), where genetic testing of FH has been performed centrally on requests from institutes all over Japan during more than past 2 decades. METHODS: 796 FH subjects from 472 families who had nonsynonymous mutations in LDL receptor gene were included in this study. Genetic mutations were analyzed for mutations by Sanger sequencing as well as by multiplex ligation probe dependent amplification technique for large rearrangements. Pathogenic mutations were defined either as 1) protein truncated variants, 2) registered as pathogenic in ClinVar, or Human Gene Mutation Database (HGMD), or meet the criteria of American College of Medical Genetics and Genomics guideline, or 3) CADD score > 10. RESULTS: We found 138 different mutations. Among them, 132 mutations were considered as pathogenic, including 19 large rearrangement mutations. However, 6 missense mutations were classified as variants of unknown significance. A single mutation accounted for as much as 41% of the FH subjects recruited from Kanazawa University mainly due to founder gene effect, whereas many singleton mutations were found from National Cerebral and Cardiovascular Center Research Institute located in Osaka. CONCLUSIONS: We provided the largest catalog of pathogenic mutations of LDL receptor gene in Japanese FH. This could aid to determine the pathogenicity of the LDL receptor genetic mutations not only in Japanese but also in other ethnicities. (C) 2020 National Lipid Association. All rights reserved.