Preventive cardiologyComparison of Genetic Versus Clinical Diagnosis in Familial Hypercholesterolemia
Section snippets
Methods
From May 2004 to November 2007, all consecutive subjects aged ≥14 years who were evaluated at 3 large lipid clinics located in university hospitals in Spain and underwent the FH genetic diagnostic procedure using Lipochip were included in the study. Subjects underwent genetic studies when the attending physician suspected FH because of familial very high total cholesterol or LDL cholesterol levels, with or without familial or personal histories of premature CAD and with or without tendon
Results
Table 1 lists the clinical characteristics and lipid profiles of the study population. There were 366 subjects (44.4%) with clinical suspicion of FH in whom the results for mutations were negative and 459 subjects (55.6%) with functional mutations in the LDLR or APOB genes. FH mutation carriers (LDLR/APOB+) were younger than those without genetic defects (LDLR/APOB−). Women predominated in the LDLR/APOB+ group. Classic clinical features of FH, such as family history of premature coronary or
Discussion
In this work, we performed phenotype-genotype comparisons in 825 subjects with clinical suspicion of FH, of whom 56% had the diagnosis genetically confirmed. We found that histories of TX in patients or their relatives was highly predictive of the presence of molecular defects in the LDLR or APOB gene in those aged >14 years with LDL cholesterol levels ≥190 mg/dl. We also defined age-specific LDL cholesterol thresholds with good predictive power for a genetic diagnosis in subjects without
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This study was supported by grants PI05/0247, PI06/0365, PI06/1402 (Fondo de Investigaciones Sanitarias de la Seguridad Social) and RTIC C06/01 (Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares) from the Spanish Ministry of Health, Madrid, Spain, and grant SAF2005-07042 from the Spanish Ministry of Education and Science, Madrid, Spain.