Tóm tắt Luận án Tiến sĩ: Mối liên quan kiểu gen - kiểu hình tăng cholesterol máu gia đình

Familial Hypercholesterolemia (FH) is a widespread genetic disorder causing high LDL-C and premature atherosclerotic cardiovascular disease. Genetic testing is crucial for early diagnosis, differential diagnosis, and personalized treatment. However, significant knowledge gaps exist regarding FH's genetic landscape and its clinical manifestations in the Vietnamese population. This study addresses these gaps by investigating the genotype-phenotype association in familial hypercholesterolemia, aiming to characterize its clinical and genetic features and evaluate their relationships, thereby improving diagnostic and therapeutic strategies in Vietnam.

Nghiên cứu sinh, giảng viên y học, bác sĩ nội khoa, tim mạch, di truyền, và các nhà khoa học quan tâm đến bệnh tăng cholesterol máu gia đình và di truyền học lâm sàng.

This doctoral thesis investigates the genotype-phenotype association in familial hypercholesterolemia (FH) within the Vietnamese population, a critical area given the disease's high prevalence and underdiagnosis in the region. The study aimed to comprehensively characterize the clinical and subclinical (phenotypic) features of FH patients, identify specific genetic variants (genotypes) in the LDLR, APOB, and PCSK9 genes, and evaluate their correlations. A cross-sectional descriptive study was conducted on 110 FH patients. Researchers employed genetic testing techniques, including Sanger sequencing, NGS, and MLPA, to detect mutations in the target genes. Clinical and subclinical data were meticulously collected and analyzed, including lipid profiles, cardiovascular manifestations, and demographic information, adhering to established diagnostic criteria like the Dutch Lipid Clinic Network (DLCN) score. The research successfully identified 28 distinct genetic mutations, including 3 novel variants, across the LDLR (21), APOB (6), and PCSK9 (1) genes. Significant genotype-phenotype associations were observed, revealing that patients with homozygous genotypes exhibited markedly higher LDL-C levels and an earlier onset of clinical manifestations, including coronary artery disease, compared to those with heterozygous or wild-type genotypes. The study also proposed specific DLCN and LDL-C thresholds to suggest the presence of a mutation or a homozygous state. These findings are pivotal for enhancing the efficacy of FH screening, diagnosis, and particularly for enabling personalized treatment strategies in Vietnam, thereby contributing to better patient management and preventing premature atherosclerotic cardiovascular disease.