MUTATIONS IN THE LOW-DENSITY-LIPOPROTEIN RECEPTOR GENE IN SWEDISH FAMILIAL HYPERCHOLESTEROLEMIA PATIENTS - CLINICAL EXPRESSION AND TREATMENT RESPONSE

Background Familial hypercholesterolaemia, an autosomal co-dominant di sorder caused by defects in the low-density lipoprotein receptor gene, is strongly associated with premature development of cardiovascular d isease. Methods In this study, we have applied a gene screening method in a population of familial hypercholesterolaemia patients in order t o describe the genetic background of the disease in southern Sweden. T hese patients were studied with the aim of relating the presence of th e different mutations to the clinical expression of the disease and to the response to pharmacological treatment. Results In 16 out of 21 pa tients, potentially disease-causing low-density lipoprotein receptor g ene defects were found, including five not previously described altera tions (C240-->F, C122-->stop, C356-->Y, 785insG, 165delG). No defects in apolipoprotein B were found. One group of patients (n = 4) carried the mutation C122-->stop and another group of patients (n = 4) a mutat ion causing the substitution W66-->G. Patients in the two genotype sub groups were very similar with respect to lipid levels before treatment . Conclusion A tendency towards differential susceptibility to treatme nt with statins was observed for the patient groups, encouraging furth er comparative studies of heterozygous FH patients.