Application of the 6-SNP elevated LDL-cholesterol polygenic risk score in individuals with familial hypercholesterolemia phenotype from an Argentine population.

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.