Apolipoprotein C-III and E Polymorphisms and Cardiovascular Syndrome, Hyperlipidemia, and Insulin Resistance in Renal Transplantation

Abstract

Hyperlipidemia and insulin resistance frequently develop after renal transplantation, contributing to cardiovascular disease. Individual differences in response based upon genetic variations in proteins regulating lipidic and glucose tolerance metabolism could be expected. In the general population, the S2 allelic variant of the apoprotein (apo) C-III gene has been associated with hypertriglyceridemia and an insulin resistant state, whereas the E4 allele of the apo E has been associated with hypercholesterolemia and atherosclerosis. Its influence in renal transplant patients remains to be seen. In order to assess the impact of apo E and C-III major polymorphisms on atherosclerotic vascular disease, lipid profile and impaired glucose tolerance in renal transplant patients, we studied 110 consecutively examined patients undergoing kidney transplantation (age range 24-73 years). Atherosclerotic complications were detected in 25% of patients, with age, male sex and hypercholesterolemia being significant atherosclerotic risk factors. Among the male patients with E4 allele, the odds ratio for coronary disease and global atherosclerosis were 10.2 (95% CI) and 6.4 (95% CI), respectively. There were no significant differences in the frequency of any of the polymorphisms among patients with dyslipidemia and impaired glucose tolerance. As the number of patients in our sample was small, larger studies are needed to verify these issues. While in the studied population C-III polymorphism appears to have little association with the prevalence of atherosclerotic complications, E4 allele should be considered as a genetic marker of coronary artery disease and global atherosclerosis in renal transplant patients.

Associations of the APOC3 rs5128 polymorphism with plasma APOC3 and lipid levels: a meta-analysis

“…Twenty-six studies [ 12 , 14 - 18 , 20 - 23 , 25 - 30 , 32 , 35 , 39 - 41 , 43 , 44 , 46 - 48 ], 10 studies [ 11 , 19 , 24 , 33 , 34 , 37 , 38 , 42 , 45 , 49 ] and 6 studies [ 13 , 31 , 36 , 50 - 52 ] involved Caucasians, Asians, and the subjects of other ethnic origins, respectively. Seven studies [ 12 , 16 , 21 , 22 , 30 , 35 , 50 ] only involved males, and the other 35 studies involved both males and females, among which 9 studies [ 14 , 23 , 26 , 28 , 29 , 36 , 37 , 43 , 47 ] separately provided data for males and females. Three studies [ 20 , 36 , 47 ] involved children.…”

“…Four studies [ 18 , 33 , 38 , 48 ] and 9 studies [ 12 , 15 - 17 , 19 , 34 , 35 , 38 , 50 ] involved type 2 diabetes and CVD, respectively. Twenty-three studies [ 12 , 14 - 17 , 19 , 23 , 25 , 26 , 28 , 29 , 34 - 38 , 43 , 45 , 47 - 50 , 52 ] separately provided data for more than one subpopulation, and each subpopulation was treated as a separate comparison. Genotype distribution in 6 populations or subpopulations [ 25 , 27 , 31 , 38 , 50 , 51 ] significantly deviated -from HWE.…”

The ApoAI-CIII-AIV gene cluster and its relation to lipid levels in type 2 diabetes mellitus and coronary heart disease: determination of a novel susceptible haplotype

“…This finding is in agreement with many studies that have demonstrated that the S2 allele of ApoC-III/SstI polymorphism is associated with CHD in type 2 diabetes; [5][6][7] however, this association was not found by others. 23,24 The P2 allele has also been found to be associated with CAD by some 16,25 but not by others. 26,27 In our study, possession of the P2 allele does not appear to influence CHD risk in diabetes.…”

Metabolic Syndrome and Transplantation

“…Finally, the presence of apolipoprotein C‐III and E polymorphisms, genetic markers associated with insulin resistance and abnormal lipid profile in the general population respectively, have failed to show any significant correlation with these metabolic abnormalities in a posttransplantation setting (9). Although likely to be underpowered, this study highlights the difficulty of translating findings from the general population to solid‐organ transplant recipients.…”