RESUMEN
AIM: Our previous study demonstrated that the endothelial lipase (EL) C.584C>T polymorphism (rs2000813, p.Thr111Ile) was significantly associated with diabetic retinopathy (DR). The present work was conducted to see if this specific variant of the EL gene was more specifically linked to the severity of DR. METHODS: This retrospective cohort study was based on a review of the institutional charts of 287 type 2 diabetes patients (mean age = 59.7 years; mean BMI = 29.0 kg/m(2); mean HbA1c=8.4%) genotyped for the EL C.584C>T polymorphism (rs2000813, p.Thr111Ile). The stage of DR was also determined for each genotype (CC, CT, TT). RESULTS: On univariate analysis, the minor allele homozygote TT variant was significantly associated with severe DR (OR: 4.3; 95% CI: 1.4, 13.1) compared with the major CC homozygote. No significant result was found for the CT heterozygote. Multivariate analysis revealed an increased risk for TT homozygotes to present with severe non-proliferative DR (OR: 8.09; 95% CI: 1.23, 53.1) or proliferative DR. Other associations were not significant. CONCLUSION: Minor allele homozygosity for this EL variant (c.584C>T) could be a significant risk factor for developing severe, sight-threatening disease due to proliferative DR. Further prospective studies of this EL polymorphism in a larger population sample are needed to confirm these results.
Asunto(s)
Diabetes Mellitus Tipo 2/genética , Retinopatía Diabética/genética , Lipasa/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Estudios RetrospectivosRESUMEN
AIM: Endothelial lipase (EL) is a key enzyme in lipid metabolism, and a polymorphism in the EL gene may be a candidate for modulating lipid parameters in type 2 diabetic (T2D) patients. METHODS: In 396 T2D patients (age: 59.5 ± 10.7 years; BMI: 28.9 ± 5.3 kg/m(2); HbA(1c): 8.2 ± 1.9%), the c.584C>T polymorphism (rs2000813, p.Thr111Ile) was studied in 225 men (frequency of c.584T: 0.351) and 171 women (frequency of c.584T: 0.304). Patients' metabolic parameters, and macrovascular and microvascular complications, were assessed at baseline and at follow-up (mean: 4.2 years). RESULTS: Patients who were homozygous for the minor allele displayed modestly decreased low-density lipoprotein (LDL) cholesterol and raised apolipoprotein B at baseline, and raised systolic blood pressure and high-density lipoprotein (HDL) cholesterol on follow-up. Homozygosity for the minor allele was significantly associated with frequency of retinopathy (P=0.025), with TT homozygous patients more likely to have diabetic retinopathy (OR: 3.505; 95% CI: 1.491-8.239) both initially and at follow-up. CONCLUSION: The c.584C>T EL polymorphism is associated with a higher risk of diabetic retinopathy that could be linked to modifications in HDL-cholesterol metabolism and blood pressure levels.
Asunto(s)
Diabetes Mellitus Tipo 2 , Angiopatías Diabéticas , Retinopatía Diabética , Lipasa/genética , Lipasa/metabolismo , Anciano , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Angiopatías Diabéticas/epidemiología , Angiopatías Diabéticas/genética , Angiopatías Diabéticas/metabolismo , Retinopatía Diabética/epidemiología , Retinopatía Diabética/genética , Retinopatía Diabética/metabolismo , Endotelio Vascular/enzimología , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad/epidemiología , Genotipo , Homocigoto , Humanos , Metabolismo de los Lípidos/genética , Estudios Longitudinales , Masculino , Microcirculación/fisiología , Persona de Mediana Edad , Polimorfismo Genético , Factores de RiesgoRESUMEN
AIM: Lipoprotein lipase (LPL) is a key enzyme of lipid metabolism, and its genetic polymorphism may be a candidate for modulating lipid parameters in type 2 diabetic subjects (D2). METHODS: In a group of 404 type 2 diabetic patients, aged 59.5+/-10.8y, BMI=28.9+/-5.3 kg/m2, HbA1c=8.2+/-1.9%, we studied the H and P polymorphisms at the LPL locus detectable with the restriction enzymes HindIII and PvuII. Patients were separated into 229 males (17H1H1, 84H1H2, 128H2H2 and 51P1P1, 110P1P2, 68P2P2) and 175 females (16H1H1, 69H1H2, 90H2H2 and 51P1P1, 85P1P2, 39P2P2), and compared on the basis of their lipid parameters and their macrovascular complications. RESULTS: Triglyceride (TG) and HDL-cholesterol(c) concentrations differed between patients with and without coronary heart disease (CHD) (3.44+/-2.09 and 1.96+/-1.40 mmol/l for TGs and 1.05+/-0.24 and 1.34+/-0.40 mmol/l for HDL-c, P<0.001). HDL-c concentrations were lower in male H2H2 and P2P2 subjects (P<0.001), and TG levels were higher in male H2H2 and P2P2 subjects (P<0.0001 for Hind III and P<0.05 for PvuII). Allele frequency of the HindIII and PvuII restriction site was similar to those reported in other Caucasian populations and the presence of the H2/P2 variants was significantly higher in CHD patients. The prevalence of CHD in this population was 18% but was 29% in H2H2 and 38% in P2P2 subjects (P<0.02). CONCLUSION: Thus, HindIII and PvuII polymorphisms seem to exert a modulating role on lipid profile particularly in male D2, contributing to increase the risk of macrovascular events.
