Apolypoprotein E gene polymorphism, gallstone disease, diabetes 2 type and lipid metabolism disorders

Abstract

Aim of the study was to explore the impact of apolipoprotein E (APOE) gene polymorphisms (GP) on gallstone disease (GSD) and type 2 diabetes mellitus (DM2) and its role in lipid metabolism. APOE4 allele carriers had the highest levels of plasma and bile cholesterol and the lowest levels of bile acids in bile than other alleles. In GSD a higher frequency of APOE4 carriers (2.6 times compared to control) was found. GSD risk was reduced by 12 % in APOE2 carriers compared to APOE3/3. Our 20-year research confirms the association of APOE GP and GSD. The frequency of ε4/ε4 genotype is higher in people aged 18–35 years with a family history of GSD (5.8 %) compared to population of Novosibirsk (1.8 %, p < 0.05). The bile was more lithogenic in APOE4 carriers with GSD: the bile cholesterol level is 8.0 ± 0.5 versus 6.9 ± 0.6 g/l in ε3/ε3 genotype. APOE4 carriers with a family history of GSD had cholate-cholesterol ratio of 6.4 ± 0.7 versus 12.9 ± 0.2 (p < 0.05) in the absence of APOE4. in women with hypertension, the presence of GSD was associated with a combination of low density cholesterol (LDL-C) > 3.5 mmol/l and the APOE4 carriage. DM2 is a recognized risk factor for GSD. The most common opinion is that the ε4 allele is an independent risk of DM2, some authors consider the allele APOE2. Moreover, DM2 patients with the ε3/ε4 genotype have an increase in total cholesterol, LDL-C and non-high-density lipoprotein cholesterol compared to ε3/ε3. Other studies have not found any associations between APOE GP and GSD or DM2. The inconsistency of the data can be explained by the heterogeneity of the included groups and methods of APOE genotyping, which requires further research.