BACKGROUND: Hypercholesterolemia (HCHL) and hypertriglyceridemia (HTRG) have emerged as the most significant metabolic consequences of therapy with sirolimus. Lipid status can be exacerbated by a variety of factors in the posttransplant setting, including genetic factors. Apoliprotein E (Apo E) polymorphism is an established genetic risk factor for hyperlipidemia. We studied the association between Apo E gene polymorphisms and lipids after kidney transplantation in patients undergoing sirolimus treatment. METHODS: We studied 98 kidney transplant patients (KTP) with stable renal allograft undergoing sirolimus treatment: 39 with HCHL and HTRG within 90 days postsirolimus treatment (PST) and 59 without hyperlipidemia PST. Apo E genotyping was performed using INNO-LiPA-ApoE. RESULTS: The cholesterol and the triglyceride values between the groups were 323.3+/-71.6 vs. 180.9+/-31.2 mg/dL (P<0.001) and 318.9+/-97.2 vs. 159.7+/-38.7 mg/dL (P<0.001). There was a significant difference in the genotype distribution of the hyperlipidemia and normal groups (P=0.009) with the percentages in each group as follows: E2/2 and E3/2: 12.8 vs. 5.1%; E3/3: 69.2% vs. 86.4%; and E4/3 and E4/4: 18.0% vs. 8.5%. We observed a higher number of patients with the genotype E3/3 in the group without hyperlipidemia PST (P=0.039). E3/2 and E4/4 genotype frequencies were higher in patients with hyperlipidemia PST. LDL levels in the hyperlipidemia PST group was statistical significant higher (P<0.001) and we observed an association between Apo E allelic distribution and LDL (P=0.005). CONCLUSIONS: Genetic factors, as Apo E genotypes, could allow the early identification of patients who are at a high risk for developing hyperlipidemia PST.
BACKGROUND:Hypercholesterolemia (HCHL) and hypertriglyceridemia (HTRG) have emerged as the most significant metabolic consequences of therapy with sirolimus. Lipid status can be exacerbated by a variety of factors in the posttransplant setting, including genetic factors. Apoliprotein E (Apo E) polymorphism is an established genetic risk factor for hyperlipidemia. We studied the association between Apo E gene polymorphisms and lipids after kidney transplantation in patients undergoing sirolimus treatment. METHODS: We studied 98 kidney transplant patients (KTP) with stable renal allograft undergoing sirolimus treatment: 39 with HCHL and HTRG within 90 days postsirolimus treatment (PST) and 59 without hyperlipidemia PST. Apo E genotyping was performed using INNO-LiPA-ApoE. RESULTS: The cholesterol and the triglyceride values between the groups were 323.3+/-71.6 vs. 180.9+/-31.2 mg/dL (P<0.001) and 318.9+/-97.2 vs. 159.7+/-38.7 mg/dL (P<0.001). There was a significant difference in the genotype distribution of the hyperlipidemia and normal groups (P=0.009) with the percentages in each group as follows: E2/2 and E3/2: 12.8 vs. 5.1%; E3/3: 69.2% vs. 86.4%; and E4/3 and E4/4: 18.0% vs. 8.5%. We observed a higher number of patients with the genotype E3/3 in the group without hyperlipidemia PST (P=0.039). E3/2 and E4/4 genotype frequencies were higher in patients with hyperlipidemia PST. LDL levels in the hyperlipidemia PST group was statistical significant higher (P<0.001) and we observed an association between Apo E allelic distribution and LDL (P=0.005). CONCLUSIONS: Genetic factors, as Apo E genotypes, could allow the early identification of patients who are at a high risk for developing hyperlipidemia PST.
Authors: Wai-Johnn Sam; Christine E Chamberlain; Su-Jun Lee; Joyce A Goldstein; Douglas A Hale; Roslyn B Mannon; Allan D Kirk; Yuen Yi Hon Journal: Transplantation Date: 2012-11-15 Impact factor: 4.939