Influence of FH Valencia 1 and 2 mutations of the LDL receptor gene on theresponse to simvastatin in subjects with molecularly defined heterozygous familial hypercholesterolemia in Spain

BACKGROUND: To analyse whether the molecular diagnosis in FH patients is us eful to predict the response to treatment with simvastatin in a south Europ ean population. SUBJECTS AND METHOD: A randomised clinical trial with no control group, wit h 20 mg/day of simvastatin was conducted in 27 genetically diagnosed FH sub jects (11 male) from 8 FH families, randomly selected from 30 FH families w ith a molecular diagnosis. Clinical features and lipid parameters at baseli ne and after simvastatin treatment were compared between subjects classifie d 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 subje cts 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 wit h null mutations. No statistically significant differences were found at ba seline, 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 p oor response to simvastatin treatment. The type of LDL receptor gene mutati on could predict the response to simvastatin in our south European FH popul ation.