Abstract 13933: Autosomal Dominant Hypercholesterolemia: A Role for Genetic Screening in Women
Background: Mutations in LDL receptor (LDLR), apolipoprotein B-100 (APOB), and proprotein convertase subtilisin-like kexin type 9 (PCSK9) cause autosomal dominant hypercholesterolemia (ADH), characterized by elevated LDL-cholesterol (LDL-C), xanthomas, and premature coronary heart disease (CHD). However, 20-60% of adult ADH patients lack an identifiable genetic cause (“unexplained” ADH), and the benefit of routine genetic screening remains unclear.
Objective: To identify phenotypic differences between patients with and without mutations in the most common ADH-causing genes: LDLR and APOB.
Methods: 182 patients (78 M, 104 F) satisfying Simon-Broome criteria were screened for mutations in LDLR and APOB. Phenotypic data, especially onset of CHD and response to lipid lowering medications, were collected.
Results: 66 patients had mutations (63 LDLR and 3 APOB) and 116 were unexplained. Consistent with prior reports, patients with LDLR mutations, as compared to the unexplained group, had higher baseline LDL-C (292 ± 61 vs. 241 ± 41 mg/dL, p < 0.001), lower baseline HDL-C (48 ± 13 vs. 53 ± 13 mg/dL, p = 0.01), and higher prevalence of xanthomas (47% vs 19%, p < 0.001). Women with LDLR mutations had earlier onset of CHD than women in the unexplained group (44 ± 12 vs. 55 ± 6 years, p < 0.01, Fig 1, Table 1) - a previously unreported finding. No such difference existed for men. Both groups responded similarly to LDL-C lowering medications (ΔLDL-C from baseline value -51% vs. -47%, p = 0.11).
Conclusion: Among patients with ADH, women with LDLR mutations suffer from earlier onset of CHD compared with women lacking an identifiable genetic cause, implying a predictive role for genetic screening.
- © 2013 by American Heart Association, Inc.