APPLICATION OF LDL GENETIC RISK SCORE IN PATIENTS WITH HYPERCHOLESTEROLEMIA TO EVALUATE A POLYGENIC ORIGIN CAUSES

BAÑARES, VIRGINIA; MARTINA, JAVIER; ALVES, CATARINA; CORRAL, PABLO; LOPEZ, GRACIELA; BERG, GABRIELA; BOURBON, MAFALDA; SCHREIER, LAURA

Mar del Plata

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2019

High LDL-cholesterol (LDL-c) values may be due to monogenic variants in the LDLR, APOB, PCSK9 or LDLRAP1 genes, leading to Familial Hypercholesterolemia (FH); or to a polygenic origin arising from polymorphisms in different genes related to cholesterol metabolism. Two genetic risk scores (GRS) are the most widely used, one in Canada (SNPs: 11) and the other in European population (SNPs: 6). Here we present the application of the European GRS in a sample of hypercholesterolemic patients in the province of Buenos Aires from the FH DaVinci study. The 6 SNPs of the GRS were obtained from the VCF files or by Sanger sequences, from 116 index cases with clinical evaluation (DCLN score) and genetic studies of FH. Twentyu eight % showed a positive GRS. The mean value was: 0.68 ± 1.72, median=0.704, mode=0.760. The quartiles values were: Q1= 0.581, Q2= 0.704 and Q3= 0.798. The SNP with the strongest effect on the score was the rs6511720 G allele on the LDLR gene (frequency 0.95). Four groups were considered: with monogenic origin (22); non-monogenic and GRS- (62); non-monogenic and GRS+ (26); and both monogenic and GRS+ (6). DLCN score was: 9.14 ± 2.98; 6.47 ± 2.53; 6.72 ± 1.90 and 10.71 ± 3.15 respectively, (ANOVA p