Increased Prevalence of Apolipoprotein E3/E4 Genotype among Swedish Renal Transplant Recipients

Abstract

There is increasing evidence that lipoproteins are involved in the progression of kidney diseases and in the deterioration of kidney transplant function, although the exact mechanism is still not known. Common polymorphisms of apolipoprotein E genotype associate with the variability of lipoprotein levels and composition. We have, therefore, determined the apolipoprotein E genotype in a group of 112 renal transplant patients, of whom 27 had had an episode of acute vascular rejection, while 85 had not. We found no difference in apolipoprotein E genotype distribution or in relative allele frequency in the vascular rejection group as compared with the group without vascular rejection. The apolipoprotein E genotype distribution in the transplant group was also compared with that in a group of 407 healthy Swedish individuals. The E3/E4 genotype occurred with a significantly increased frequency in the transplant group: 38.3 versus 16% in the control group (p < 0.001). The prevalence of individuals carrying the Ε4 allele among the transplant group was also significantly higher (44%) as compared with the control group (30%; p < 0.01). This increase was entirely due to the predominant increase of E3/E4, as the E4/E4 genotype was less frequent in transplant recipients than in normal controls (3.5 vs. 10.6%; p < 0.05). The relative frequencies of Ε2 (0.044), Ε3 (0.716), and Ε4 (0.238) alleles in the renal transplant group were not different from those of normal controls (0.078, 0.718, and 0.202, respectively). With regard to the prevalence of E4/E4 in the two groups, the lack of difference in the relative frequency of the Ε4 allele must be interpreted with caution. The results thus suggest that the E3/E4 genotype may be associated with the progression of kidney disease leading to renal insufficiency. However, the apolipoprotein E genotype does not seem to influence the risk of vascular rejection among transplant recipients.

Association of apolipoprotein E gene polymorphism with end-stage renal disease and hyperlipidemia in patients on long-term hemodialysis

“…In fact, ESRD patients presented a lower frequency distributions of the e3 allele and the E3/E3 genotype and higher frequency distributions of the e4 allele and E3/E4 genotype than the controls. These results are in agreement with the findings in Caucasians and Swedish patients 20,21 and suggested that the e4 allele and E3E4 genotype are associated with ESRD. A weak association between the e4 allele and a low glomerular filtration rate was recently demonstrated.…”

Influence of Apolipoprotein E Genotype on Progression of Diabetic Nephropathy

“…We too found that patients with apoE3/4 progressed significantly more quickly. Another study speculated that apoE3/4 was a specific risk factor for progression of renal failure requiring transplantation after finding a significantly higher frequency of apoE3/4 genotypes in the transplant recipients [24]. …”

An African perspective on the genetic risk of chronic kidney disease: a systematic review

“…This is true for the polymorphisms investigated in the current review. For example, Lahrach et al [ 21 ] showed that the e4 allele and the E3E4 genotype of the apoE gene demonstrated a strong association with ESRD, similar to a study conducted in a Swedish population [ 46 ]. However, a study conducted in African Americans and European Americans showed an opposite effect, with the e4 allele being associated with decreased risk of ESRD progression and decreased risk of prevalent ESRD [ 47 ], with no association found between the e4 allele and CKD in Asian populations [ 48 ].…”