Virginia Bañares, Administración Nacional de Laboratorios e Institutos de Salud “Dr Carlos Malbrán”, Centro Nacional de Genética Médica, Departamento de Genética Experimental, Ciudad Autónoma de Buenos Aires, Argentina
Javier Martini, Administración Nacional de Laboratorios e Institutos de Salud “Dr Carlos Malbrán”, Centro Nacional de Genética Médica, Departamento de Genética Clínica, Ciudad Autónoma de Buenos Aires, Argentina
Graciela López, Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Bioquímica Clínica, Laboratorio de Lípidos y Aterosclerosis, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina
Pablo Corral, Universidad FASTA, Facultad de Medicina, Instituto de Investigaciones Clínicas, Mar del Plata, Buenos Aires. Argentina
Laura Schreier, Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Bioquímica Clínica, Laboratorio de Lípidos y Aterosclerosis, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina
Introduction: LDL-cholesterol greater than 190 mg/dL indicates severe hypercholesterolemia (HS) of monogenic and/or polygenic origin. Genetic risk scores (GRS) evaluate potential polygenic causes. Objective: We applied a GRS of 6-SNP (GRS-6) in HS individuals. Material and methods: 69 subjects from the Familial Hypercholesterolemia (HF) Detection registry in Argentina (Da Vinci). Results: With 44 individuals with HF-phenotype, not carriers of genetic variants that indicate a monogenic origin (HF/M−) and 26 controls, the GRS-6 cut-off value was established, > 0.76, sensitivity 0.59, specificity 0.69. 15/44(34 %) HF/M− presented GRS-6+. The mean GRS-6 values in HF/M−, HF/M+ and controls were 0.72 ± 0.17, 0.66 ± 0.17, and 0.70 ± 0.13 respectively (p = 0.43). There were no significant differences in cholesterol values, or in the clinical score, between cases with positive vs negative GRS-6. The GRS-6 was positive in 32 % of the cases vs 20 % of the previously applied GRS-10 (p = 0.003), significantly increasing the detection of polygenic contribution. Conclusions: We present an estimate of the first cut-off value for the GRS-6 in a Latin American population, and we conclude that the GRS-6 could contribute to the evaluation of the polygenic contribution in cases with severe hypercholesterolemia in our population in a similar way to that of other European populations.
Keywords: Familial hypercholesterolemia. Polygenic hypercholesterolemia. Severe hypercholesterolemia. Polygenic risk score.