期刊
JOURNAL OF CLINICAL LIPIDOLOGY
卷 12, 期 4, 页码 1039-1046出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacl.2018.04.004
关键词
Ankle-brachial index; Carotid atherosclerosis; Erectile dysfunction; Intima-media thickness; LDL-cholesterol; PCSK9; R46L
资金
- Novo Nordisk
- Fundacion para el Fomento y Desarrollo de la Investigacion Clinica (FYDIC)
BACKGROUND: The R46L variant of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene has been related to lipid levels and cardiovascular disease. OBJECTIVE: To evaluate the influence of this polymorphism on subclinical vascular disease and erectile dysfunction (ED). METHODS: We analyzed the association of the PCSK9 rs11591147 single-nucleotide polymorphism with lipid levels, intima-media thickness (IMT), and the ankle-brachial index, in 1188 adults free of cardiovascular disease, randomly selected from the population. In 473 male participants, we also investigated its relationship with ED. The association of the R46L polymorphism with lipid levels was also assessed in 2 cohorts of 1103 prepuberal children and 830 adolescents. RESULTS: The prevalence of the T allele was 2.9% in adults. Low-density lipoprotein cholesterol (LDL-cholesterol) levels did not vary according to this polymorphism (134 +/- 32 vs 134 +/- 31 mg/dL, for the TT + GT vs GG carriers, respectively, P = .931). Despite equal LDL-cholesterol levels, adults carrying the T allele had a lower mean common carotid IMT (0.685 +/- 0.09 vs 0.723 +/- 0.127 mm; P = .035), a lower maximum common carotid IMT (0.819 +/- 0.11 vs 0.865 +/- 0.159 mm; P = .040), and, in males, a lower prevalence of ED (36.8% vs 61%: P = .036), than GG carriers. Prevalence of the T allele was 3.2% in both cohorts of children. They had lower levels of LDL-cholesterol than GG subjects (100 vs 109 mg/dL; P = .060, for prepuberal children, and 85 vs 99 mg/dL; P = .010 for adolescents). CONCLUSION: In our population, an association between the PCSK9 R46L variant and LDL-cholesterol levels is observed in children. In adults, although its association with lipid levels is not evident, there is a significant relationship between the PCSK9 R46L variant and markers of subclinical atherosclerosis, including IMT and ED. (C) 2018 National Lipid Association. All rights reserved.
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