Abstract
ObjectiveEnd-stage renal disease (ESRD) is a severe health concern over the world. Associations between apolipoprotein E (apoE) gene polymorphisms and the risk of ESRD remained inconclusive. This study aimed to investigate the association between apoE gene polymorphisms and ESRD susceptibility.MethodsDatabases including PubMed, Embase, Web of Science and the Cochrane Library were searched to find relevant studies. Meta-analysis method was used synthesize the eligible studies. ResultsSixteen pertinent case-control studies which included 3510 cases and 13924 controls were analyzed. A significant association was found between ε2 allele and the ESRD risk (odds ratio (OR) = 1.30, 95% confidence interval (CI) 1.15–1.46, P < 0.0001; I 2 = 18%, P for heterogeneity = 0.24). The ε2ε3, ε2ε4, ε3ε3, ε3ε4, ε4ε4, ε3 and ε4 were not associated with the susceptibility of ESRD. In the subgroup analysis by ethnicity, there was a statistically significant association between ε2ε3 or ε2 allele and ESRD risk in East Asians (OR = 1.66, 95% CI 1.31–2.10, P < 0.0001; OR = 1.62, 95% CI 1.31–2.01, P < 0.0001, respectively), but not in Caucasians. E2 carriers had higher plasma apoE (mean difference = 16.24 mg/L, 95% CI 7.76-24.73, P = 0.0002) than the (ε3 + ε4) carriers in patients with ESRD. The publication bias was not significant.ConclusionThe ε2 allele of apoE gene might increase the risk of ESRD. E2 carriers expressed higher level of plasma apoE in patients with ESRD. More well-designed studies are needed to confirm these associations in the future.
Highlights
Patients with high level of apoE2 were more likely to develop into chronic kidney disease (CKD) or even End-stage renal disease (ESRD), because the clearances of very low-density lipoprotein (VLDL) and CM remnants were delayed by apoE2 [5]
Allele frequency from high to low is: ε3, ε2, ε4, and ε3ε3 is the most common phenotype in human [10]. It is commonly believed the ε2 allele was associated with the progressive decline of renal function, and ε4 reduced the risk of ESRD [11,12]
A significant association was found between ε2 allele and the ESRD risk
Summary
A total of 16 clinical studies [14,15,18,19,20,21,22,23,24,25,26,27,28,29,30,31] on ESRD and apoE variants published from 1992 and 2008 were identified, among which seven studies were form. A significant association was found between ε2 allele and the ESRD risk The ε2ε3, ε2ε4, ε3ε3, ε3ε4, ε4ε4, ε3 and ε4 were not associated with the susceptibility of ESRD (Table 3) Both ε4ε4 and ε4 allele showed lower risk of ESRD than the control group In the results of subgroup analysis by ethnicity, there was a statistically significant association between ε2ε3 or ε2 allele. The ε2 allele may be a risk factor of renal disease In this meta-analysis, the association between the apoE polymorphisms and ESRD risk was explored. The results indicated that individuals with the ε2 allele showed an increased risk of ESRD in the overall population. Screening of the ε2 allele might prevent the patients with CKD from progression into ESRD
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