RESUMEN
Obstructive sleep apnea (OSA) is associated with dyslipidemia and increased cardiovascular risk. We assessed the effects of apolipoprotein E ( APOE) genotype on low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle size and lipid subclasses (separated by gradient gel electrophoresis) in patients with OSA. Stable patients (n = 181) prospectively recruited underwent full polysomnography. Both LDL particle size and LDL I proportion were reduced from ∊3∊3 homozygotes to ∊2 carriers and to ∊4 carriers (analysis of variance: P = .024; P = .040, respectively); carriers of the ∊4 allele of the APOE genotype had significantly lower LDL particle size and LDL I proportion compared to ∊3∊3 homozygotes ( P < .05 for both comparisons). Insulin resistance increased from patients with no OSA to those with mild-moderate and to those with severe OSA ( P < .001). In multivariate analysis, LDL size was independently predicted by APOE genotype, male gender, and the presence of metabolic syndrome (MetS; P = .001, P = .020, P = .027, respectively). The HDL particle size was not affected by APOE genotype. Our data demonstrate that both the ∊4 APOE genotype and MetS are independently related to smaller LDL size in patients with OSA.
Asunto(s)
Apolipoproteínas E/genética , Tamización de Portadores Genéticos , Genotipo , Lipoproteínas LDL/sangre , Apnea Obstructiva del Sueño/genética , Adulto , Anciano , Apolipoproteína E4/genética , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Persona de Mediana Edad , Tamaño de la Partícula , Polisomnografía , Estudios Prospectivos , Apnea Obstructiva del Sueño/sangre , Estadística como AsuntoRESUMEN
There is increasing evidence that intermittent hypoxia resulting from obstructive sleep apnoea (OSA) is independently associated with dyslipidaemia. Currently, no data exist on potential links between OSA-related dyslipidaemia and susceptibility genes for dyslipidaemia in such patients. Our aim was to study the effects of the apolipoprotein E (APOE) genotype and sleep apnoea severity on atherogenic dyslipidaemia in patients with OSA. 519 clinically stable subjects prospectively recruited at a tertiary referral teaching hospital underwent full polysomnography. APOE gene polymorphisms were assessed using real-time PCR. In all APOE genotype groups, serum triglycerides increased while high-density lipoprotein (HDL) cholesterol was reduced with increasing severity of OSA in each APOE genotype group, whereas the deleterious effects of OSA on serum apolipoprotein (Apo)B levels were observed in ε2 carriers and the ε3/ε3 genotype only. Nevertheless, the ε4 allele carriers had ApoB levels within the risk range, irrespective of nocturnal hypoxia. In addition, among patients with the high-risk ε4 genotype, those with the most severe nocturnal hypoxia had significantly higher triglyceride and lower HDL cholesterol levels compared with nonhypoxic ε4 subjects. APOE genotype and the oxygen desaturation index were both independent predictors of serum triglyceride levels (p=0.009 and p<0.001, respectively; R(2)=0.148) and ApoB levels (p=0.001 and p=0.003, respectively; R(2)=0.104). Our findings suggest that OSA has adverse effects on several lipid parameters over and above the effects carried by APOE genotype. Further st1udies are needed to analyse the effects of high-risk genotypes on metabolic and cardiovascular outcomes in patients with OSA.
Asunto(s)
Apolipoproteínas E/genética , Dislipidemias/sangre , Dislipidemias/genética , Lípidos/sangre , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/genética , Adulto , Alelos , Dislipidemias/complicaciones , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Heterocigoto , Humanos , Hipoxia , Masculino , Persona de Mediana Edad , Oxígeno/química , Polimorfismo Genético , Polisomnografía , Estudios Prospectivos , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Riesgo , Sueño , Apnea Obstructiva del Sueño/complicaciones , Centros de Atención Terciaria , Triglicéridos/sangreRESUMEN
Patients with obstructive sleep apnea (OSA) have proatherogenic dyslipidemia. We analyzed predictors of low-density lipoproteins' (LDLs) size in patients with OSA. In a cross-sectional study including 58 participants with OSA (30 without the metabolic syndrome [MetS] and 28 with MetS), we evaluated the size of LDL by gradient gel electrophoresis. Compared with patients without the MetS, those with MetS showed lower LDL size (P = .007), due to a reduction in large LDL-I particles (P = .002) and an increase in small, dense LDL-IIIA (P = .048) and LDL-IIIB (P = .037). The size of LDL correlated inversely with age (r = -.268, P = .042) and serum triglycerides (r = -.364, P = .005), and positively with serum high-density lipoprotein cholesterol levels (r = .335, P = .010). In multiple regression analysis, the presence of the MetS was the only independent predictor of LDL size (P = 0.015). In patients with OSA, MetS is an independent predictor of LDL size and subclasses, whereas the severity of OSA does not contribute independently to alterations in LDL phenotype.
