Related Research Between LDLR/PCSK9 Genes And Hypercholesterolemia

Objective: Analyze the changes of blood lipid concentration in hypercholesterolemia and investigate the correlation between hypercholesterolemia and LDLR /PCSK9 gene, to provide laboratory and genetic basis for early prevention, diagnosis and treatment of hypercholesterolemia.Methods: The first part of this study collected 100 cases of hypercholesterolemia and 50 cases of healthy subjects as the research object. Using automatic biochemical analyzer to test the concentration of serum TC, LDL-C, Apo B100, TG, HDL–C, Lp(a) and using SPSS13.0 software to analyse the measured results. The second part used PCR and Sanger sequencing method to analyse the gene sequence of the Apo B100/ LDLR /PCSK9 gene in all of research object, the sequencing results compared to the BLAST Sequence Analysis Tool, observe the allele frequency and genotype distribution and determine the mutation site.Results: 1. The lipid concentration of hypercholesterolemia as follows: TC(7.75±1.35 mmol/ L), LDL-C(4.70±1.83 mmol/L), Apo B100(1.37±0.20 g/L), TG(1.28±0.31 mmol/L), HDL-C(1.35±0.39 mmol/L), Lp(a) [15.49±8.44 mg/d L]. The lipid concentration of normal control group as follows: TC(3.87±0.42 mmol/L), LDL-C(2.65±0.28 mmol/L), Apo B100(0.83±0.13 g/L), TG(1.23±0.30 mmol/L), HDL-C(1.26±0.18 mmol/L), Lp(a) [16.56±6.17 mg/d L]. The concentration of serum TC, LDL- C, Apo B100 in hypercholesterolemia were higher than in normal control group, the difference is statistically significant(P < 0.05). 2. Ten mutation sites were found in the analysis of the LDLR gene of patients with hypercholesterolemia, including seven synonymous mutations(p.C27 C, p.R471 R, p.P539 P,p.N591 N, p.V653 V, p.R744 R, p. S786S), two missense mutations(p.R406 Q, p.D622Y) and one premature termination codon mutation(p.E714X). Seven mutation sites were found in the analysis of the PCSK9 gene of patients with hypercholesterolemia, including three synonymous mutations(L112L, V460 V, C626C), three missense mutations(p.R93 C, p.V474 L, p.G670E) and one frameshift mutation(416-417 ins CTG).Conclusions: 1. The concentration of serum TC, LDL-C and Apo B100 in hypercholesterolemia group was significantly higher than that of normal control group, it can be used as a laboratory reference basis for clinical diagnosis of hypercholesterolemia. 2. No mutation sites were found in the analysis of LDLR/PCSK9 gene in normal control group. In the analysis of the LDLR/PCSK9 gene of patients with hypercholesterolemia, the detected mutations of LDLR gene(p.R406 Q, p.D622 Y, p.E714X) and PCSK9 gene(416-417 ins CTG, p.R93 C, p.V474 L, p.G670E) may be associated with the occurrence of hypercholesterolemia.