Apolipoprotein E genotypes as predictors of high-risk groups for developing hyperlipidemia in kidney transplant recipients undergoing sirolimus treatment.
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.
Maluf
Daniel G
DG
Division of Transplantation, Department of Surgery, Virginia Commonwealth University, Richmond, VA 23298-0248, USA. dgmaluf@vcu.edu
Mas
Valeria R
VR
Archer
Kellie J
KJ
Yanek
Kenneth
K
King
Anne
A
Ferreira-Gonzalez
Andrea
A
Fisher
Robert A
RA
Posner
Marc
M
D000328:Adult; D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006949:Hyperlipidemias / Q000139:chemically induced / Q000453:epidemiology* / Q000235:genetics; D007166:Immunosuppressive Agents / Q000009:adverse effects; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D020123:Sirolimus / Q000009:adverse effects*; D014280:Triglycerides / Q000097:blood; D014768:Virginia
D001057:Apolipoproteins E; D007166:Immunosuppressive Agents; D008077:Lipoproteins, LDL; D014280:Triglycerides; D002784:Cholesterol; D003404:Creatinine; D020123:Sirolimus