Credit Seminar on Role Of Pcsk9 and Arh Genes in Familial Hyper cholesterolemia

Familial hypercholesterolemia (FH) is a metabolic inherited autosomal dominant disorder that causes severe elevation in the total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels. Because FH is associated with a high risk for premature coronary heart disease (CHD), early detection and aggressive management is required to lower the LDL-C level to prevent or slows the progression of coronary atherosclerosis. The major players in FH are LDL receptor (LDLR) and Apolipoprotein B (ApoB) genes, mutations in these genes are responsible for around 97% of FH cases. There are other genes also which are involved like PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) and LDLRAP1 (LDLR adaptor protein 1). PCSK9 protein plays a major regulatory role in cholesterol homeostasis by binding to LDLR and inducing LDLR degradation. Reduced LDLR levels result in decreased metabolism of LDL, which could lead to hypercholesterolemia. LDLRAP1 protein interacts with LDLR through PTB domain and helps in the endocytosis of LDLR. Mutations in this gene lead to LDL receptor malfunction and cause the disorder autosomal recessive hypercholesterolemia. Although mutations in both PCSK9 and LDLRAP1 genes are rare, these genes are involved in cholesterol homeostasis and can be used as a drug targets for lowering plasma cholesterol level. For this potential use of PCSK9 and LDLRAP1, the structure and functional mechanism of them need to be studied in detail. In this report, the structural and functional aspects of PCSK9 and LDLRAP1; and their possible uses in therapeutics have been discussed.

 Name: Vidhi Makani
 Reg.No: 1741110033
 Guide Name: Mr.N.Arul Jothi
 Date: 6.09.12
 Time: 3.20 PM
 Venue: Room No: 701(B)