Familial hypercholesterolemia in Gran Canaria: Founder mutation effect and high frequency of diabetes

Abstract

Introduction: Gran Canaria is a region of genetic isolation of familial hypercholesterolemia due to a founder mutation, p. [Tyr400_Phe402del], in the LDL receptor (LDLR) gene. Initial data suggest that its carriers could have a high prevalence of diabetes.

Material and methods: Patients over 30 years of age with familial hypercholesterolemia and a confirmed mutation in LDLR were recruited from a tertiary hospital in Gran Canaria. The prevalence of diabetes and other clinical data were compared among carriers of p. [Tyr400_Phe402del] and those with other LDLR mutations.

Results: 76.4% of the 89 participants were carriers of p.[Tyr400_Phe402del]. The prevalence of diabetes in this group was significantly higher (25 vs. 4%, P=.045). These cases also had a higher prevalence of cardiovascular disease and higher levels of LDL cholesterol and triglycerides. There were no differences in age, weight, body mass index, waist, age of onset, and time of statin treatment. However, they required PCSK9 inhibitors more often (51.5 vs 24%, P=.027).

Conclusions: The mutation p.[Tyr400_Phe402del] is associated with a high prevalence of diabetes, not explained by classic risk factors, such as age, obesity, or long-term use of statins.

Keywords: Cardiovascular disease; Diabetes; Efecto fundador; Enfermedad cardiovascular; Familial hypercholesterolemia; Founder effect; Hipercolesterolemia familiar.