Influencia de las mutaciones HF Valencia 1 y 2 del gen del receptor de LDL sobre la respuesta terapéutica a simvastatina en sujetos con hipercolesterolemia familiar heterocigota caracterizada molecularmente

Background: To analyse whether the molecular diagnosis in FH patients is useful to predict the response to treatment with simvastatin in a south European population.

Subjects and Method: A randomised clinical trial with no control group, with 20 mg/day of simvastatin was conducted in 27 genetically diagnosed FH subjects (11 male) from 8 FH families, randomly selected from 30 FH families with a molecular diagnosis. Clinical features and lipid parameters at baseline and after simvastatin treatment were compared between subjects classified as null mutations (FH Valencia 1 and 2; n = 11) and defective mutations (n = 16).

Results: FH with null mutations (FH Valencia 1 and 2) have a poor response to simvastatin treatment. The mean reduction of plasma LDLc levels in subjects with null mutations were significantly lower (32.6% [9.5] vs 42.8% [12.2]; p = 0.03) than in subjects with defective mutations. Baseline and after treatment plasma HDLc values were also significantly lower in FH group with null mutations. No statistically significant differences were found at baseline, after treatment and in the response to treatment between males and females.

Conclusions: FH subjects with null alleles (FH Valencia 1 and 2) showed a poor response to simvastatin treatment. The type of LDL receptor gene mutation could predict the response to simvastatin in our south European FH population.