LDLR Gene Mutation Analysis Of Patients With Hypercholesterolemia And Coronary Heart Disease

Purpose:By studying patients with hypercholesterolemia, LDLR gene mutation rate will bediscussed, hoping to make identification of new kinds of LDLR gene mutations. Inaddition, to provide the molecular diagnostic basis for coronary heart disease inhypercholesterolemia patients, and the guidance for targeted gene therapy of coronaryartery diseases as well.Methods:We screened126patients with hypercholesterolemia from1,400patients withcoronary heart disease in Shandong province, and we analyzed all the Exon mutations ofLDLR gene by PCR and DNA sequencing methods.(1)1,400coronary heart diseasepatients were screened, so as to a normal control group of2,000cases. Clinical data wererecorded for future use.(2)We performed lipid analysis in patients with coronary heartdisease and normal control group, picking out126of the patients whose total cholesterol(TC) were higher than6.2mmol/L.(4) The LDLR gene PCR amplification wasconducted, while DNA sequencing analysis was performed.(5) We compared thesequences using BLAST and artificial methods.Results:We found10different LDLR mutations in17cases of patients that were sufferingfrom both coronary heart disease and hypercholesterolemia;. c.1088C>T was one of thenovel mutations, which changed Threonine to Isoleucine; the other was a synonymousmutation, which was c.1002C>T. The reported mutations we found werec.292G>A,c.769C>T, c.1056C>T, c.1291G>A, c.1413A〉G, c.1617C〉T, c.1773C〉T,c.2232A〉G. Among the4cases of missense mutations we found, Gene mutations on Exon3andExon5change the LDLR ligand binding domain, Gene mutations on Exon8and Exon9change LDLR EGF precursor domain. Ligand binding domain is the main part of LDLbinding to LDLR. And the EGF precursor domain is a necessary part for receptor andligand in the cytoplasm endosome acid-dependent dissociation, while assisting LDLRligand binding domain to identify LDL. Therefore, missense mutations on the abovepositions may have a greater impact on the LDLR’s identification of LDL and thecirculation of itself, leading to an increase in plasma cholesterol. The LDLR mutations wefound will contribute to early diagnosis and treatment of the hypercholesterolemia.