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    • Apo E is defined as a polym

    2021-11-26

    Apo E is defined as a polymorphic protein arising from three alleles. The human Apo E gene was widely studied and described to be located on chromosome 19, closely linked to the Apo C-I/C-II gene complex [9]. The three major alleles, termed Epsilon-2, Epsilon-3 and Epsilon-4 have been reported [10]. The apoE2, apoE3 and apoE4 protein isoforms, corresponding products of these alleles, differ only by a single amino EX 527 mg at two residues. Where Apo E2 contains cysteine at two residue 112 and 158 and Apo E4 has arginine at both positions while apoE3 has cysteine at residue 112 and arginine at residue 158 [11]. Less than 0.1% of the population have additionally, two minor alleles of the gene, ε1 and ε5. Three homozygous (E2/E2, E3/E3, E4/E4) and three heterozygous (E2/E3, E2/E4, E3/E4) genotypes will be determined by these three major alleles [12].
    Material and methods
    Results Comparison of lipid profile between the chronic HCV cases and subjects with SVR were summarized in Table 1. There were statistically significant differences between the two groups regarding cholesterol and LDL serum levels where patients with chronic HCV infection had lower level of cholesterol and LDL compared to the subjects with SVR (P < .001), while no statistically significant differences as regards triglyceride, HDL and VLDL serum levels were demonstrated. The distribution of Apo E genotype frequencies, allele frequencies and risk association were compared between the two groups and summarized in Table 2. Statistically significant differences were demonstrated regarding the Apo E genotypes between the two groups (P-value < .001) where the frequency of E3E3 was significantly higher among the chronic HCV-patients while E3E4 and E4E4 genotypes frequencies were higher among the SVR-subjects group (P-value < .001) and E3E3 genotype was associated with increased risk of chronicity (OR 4.7; 95% CI 1.9–12.1). Moreover, There were statically significant differences regarding E3 and E4 alleles frequencies, where E3 allele display a higher frequency among the chronic HCV-patient group while the SVR-subjects group showed higher frequency of E4 allele (P-value < .05). Demonstration of the risk association of the different Apo E alleles and HCV chronicity among the studied groups showed that carriers of E3 allele have 1.4 times more risk to develop chronicity than those with E4 allele (OR 1.4; 95% CI 1.0–2.0). Meanwhile the protective E2 allele was absent in all infected participants. Comparison of the serum levels of lipid profile among the different genotypes were demonstrated and shown in Table 3. Although the serum level of total cholesterol and LDL is lower in E3 carrier allele than those with E4 carriers, yet the difference is not statistically significant.
    Discussion Apolipoprotein E – a major structural LDL component and natural ligand of LDLR – which is intimately linked to plasma lipoprotein metabolism and may have an impact on the course of HCV infection. Three isoforms of Apo E have been identified E2, E3 and E4. Whereas the salt bridge formation within the proteins could be affected by the amino acid substitutions, which modulate the lipoprotein preference, protein stability and isoform receptor binding activities, the apoE genotypes may have a significant impact on HCV pathology and prognosis [19]. Linkage of the functional host-specific genetic polymorphisms within Apo E may influence the interaction between the host and HCV, and subsequently the outcome of HCV infection [20]. These findings not only assuming that that Apo E3 allele was associated with chronic outcome of HCV infection but also conferred a better chance of Apo E4 allele carriers to recover after convenient therapy and highlights the already established hypothesis that decreased LDL-R expression in E4 vs. E3 carriers could diminish viral maturation [21]. In concordance with this result, Price et al., 2006 who reported that E3E3 genotype is associated with highest risk of developing a chronic HCV infection in Caucasian hepatitis C patients, while E4 alleles is favoring viral clearance (the odds ratio was 0.59) [22]. Likewise, Mueller et al., 2016 concluded reduction of the susceptibility to chronic HCV infection in Apo E4 allele carriers [20]. Moreover, Teama et al., 2016 supported the possible genetic association between ApoE 4 allele with a lower probability of progression to HCV-related liver cirrhosis [23]. With the same respect, Kuhlmann et al., 2010 reported that the HCV-specific protective effect of apoE4 genotype and better outcome of chronic HCV infection justified by the slower fibrosis progression among E4 carriers [24].