Associations between pathogenic variant (PV) positivity and 4-single nucleotide polymorphism (SNP) score were established in patients with familial hypercholesterolemia (FH) in response to lipid-lowering therapy (LLT), according to study results published in Scientific Reports.

Researchers sought to analyze the relationship between genetic characteristics and the response to LLT in patients with FH. The study’s primary variable was the achieved percentage of expected response to LLT.

Of 146 patients enrolled in the Korean FH registry, 83 patients (mean age, 53 years; 60% women) who had undergone appropriate LLT escalation and were followed for ≥6 months were analyzed for PVs. The achieved percentage of expected low-density lipoprotein cholesterol (LDL-C) reduction (primary variable) and rates of achieving LDL-C levels <70 mg/dL were assessed.

Putative PVs were identified in 30 patients (36%). The median baseline LDL-C was higher among carriers of PVs compared with that in the PV-negative patients (246 mg/dL vs 206 mg/dL, respectively; P <.001).

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The primary variables were significantly lower in PV-positive vs PV-negative patients (P =.007), although the type of PV did not significantly correlate with the primary variable. Rates of achieving LDL-C <70 mg/dL were very low, regardless of PV characteristics. Patients who had a higher 4-SNP score had a lower primary variable (R2 = 0.045; P =.048).

“Among evolocumab users, PV-negative patients or those with only defective PVs revealed higher primary variable, whereas patients with at least 1 null PV showed lower primary variable,” noted the investigators.

Study limitations include the fact that the effects of other SNPs of the same genes or other lipid-related genes cannot be ruled out.

“Our findings indicate that adjusted response to LLT has significant associations with PV positivity and the 4-SNP score,” concluded the investigators. “The results obtained in this study may ensure effective and individual management of [patients with] FH with diverse genetic backgrounds.”


Kim H, Lee CJ, Pak H, et al. GENetic characteristics and REsponse to lipid‑lowering therapy in familial hypercholesterolemia: GENRE‑FH study. Sci Rep. 2020;10(1):19336.