Detection of the Splicing Defects (c.1845+11C>G) and Common Polymorphism (1773C>T) in Exon 12 of the LDL-R Gene on Chromosome 19 among Some Heterozygous FH Patients in Tripol
Keywords:
Familial Hypercholesterolemia (FH), Single Nucleotide Polymorphism (SNP), Exon 12, Lipoprotein metabolism, Genetic mutationAbstract
This study investigates the genetic basis of familial hypercholesterolemia (FH) in selected Libyan patients in Tripoli, focusing on variants associated with mutations in exon 12 of the low-density lipoprotein receptor (LDL-R) gene on chromosome 19. Genetic analysis was performed using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) based on DNA techniques to detect splicing defects of the LDL-R gene in exon 12. Participants were recruited from the Tajoura National Cardiac Center and the Endocrine and Diabetic Hospital in Tripoli. The results revealed the presence of the splicing defect (c.1845+11C>G) in exon 12 of the LDL-R gene in patients with hypercholesterolemia and ischemic heart disease, many of whom had a family history of hypercholesterolemia and other contributing factors such as diabetes, hypertension, chest pain, and obesity. The frequency of heterozygous FH patients in the sample was 0.86%, with statistical analysis showing {p-value > 0.05}, which is considered high according to clinical diagnostic criteria. In addition, the study detected the single nucleotide polymorphism (SNP) (1773C>T), which alters exon splicing efficiency and is linked to emerging functional genetic variants in exon 12. Molecular diagnosis confirmed that LDL-R gene mutations are strongly associated with premature coronary artery disease (P-CAD).
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