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Apolipoprotein E genetic polymorphism influence the susceptibility to nephropathy in type 2 diabetes patients.
Gene. 2019 Oct 05; 715:144011.GENE

Abstract

BACKGROUND

An association between Apolipoprotein E (Apo E) alleles and genotypes and diabetic nephropathy (DN) was suggested, but with inconsistent results. We tested the relationship between serum lipids, Apo E alleles and genotypes with type 2 diabetes (T2DM), and DN pathogenesis.

METHODS

Study subjects comprised 1389 normoglycemic controls, and 1422 T2DM patients, of whom 825 were normoalbuminuric (DWN), and 597 presented with nephropathy (DN).

RESULTS

Significantly lower Apo ε2, and higher Apo ε4 allele frequencies was seen among T2DM patients than controls. Significantly higher frequency of ε3/ε4, and lower frequencies of ε3/ε3, ε2/ε3, and ε4/ε4 carriers was seen among T2DM cases. Apo ε2-carrying individuals were more frequently found in controls than in patients, while significantly higher frequency of ε4-carrying genotypes was seen in T2DM cases. Significantly higher ε2, and lower ε3 allele frequencies were noted for DN group compared to DWN group. Significantly higher frequency of ε2-containing ε2/ε3 and ε2/ε4, and lower frequencies of ε3/ε3 carriers was seen among DN cases. Apo ε3/ε3 was associated with higher total cholesterol, LDL-cholesterol, and triglyceride levels in DN patients, and significantly higher triglyceride levels were seen in ε2/ε3-carrying DN patients. Logistic regression analysis confirmed the association of Apo ε3-containing ε3/ε3, ε2/ε3, and ε3/ε4, and Apo ε2-containing ε2/ε4 with DN, after controlling for key covariates.

CONCLUSION

The results of this case-control study provide evidence that the ε2 and ε3 alleles of APOE modify lipid profile, and constitute independent risk factors of DN in type 2 diabetes. The molecular mechanisms underlying this risk is discussed.

Authors+Show Affiliations

School of Medicine, Nazarbayev University, Astana, Kazakhstan.Department of Internal Medicine, LAU Medical Center - Rizk Hospital, Beirut, Lebanon.Department of Adult Endocrinology and Diabetes, Rafic Hariri University Hospital, Beirut, Lebanon.St. Marc Medical Center, Beirut, Lebanon.College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain; Faculty of Sciences, El-Manar University, Tunis, Tunisia.School of Medicine, Nazarbayev University, Astana, Kazakhstan; Faculty of Sciences, El-Manar University, Tunis, Tunisia. Electronic address: wassim.almawi@outlook.com.

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study

Language

eng

PubMed ID

31357022

Citation

Atageldiyeva, Kuralay K., et al. "Apolipoprotein E Genetic Polymorphism Influence the Susceptibility to Nephropathy in Type 2 Diabetes Patients." Gene, vol. 715, 2019, p. 144011.
Atageldiyeva KK, Nemr R, Echtay A, et al. Apolipoprotein E genetic polymorphism influence the susceptibility to nephropathy in type 2 diabetes patients. Gene. 2019;715:144011.
Atageldiyeva, K. K., Nemr, R., Echtay, A., Racoubian, E., Sarray, S., & Almawi, W. Y. (2019). Apolipoprotein E genetic polymorphism influence the susceptibility to nephropathy in type 2 diabetes patients. Gene, 715, 144011. https://doi.org/10.1016/j.gene.2019.144011
Atageldiyeva KK, et al. Apolipoprotein E Genetic Polymorphism Influence the Susceptibility to Nephropathy in Type 2 Diabetes Patients. Gene. 2019 Oct 5;715:144011. PubMed PMID: 31357022.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Apolipoprotein E genetic polymorphism influence the susceptibility to nephropathy in type 2 diabetes patients. AU - Atageldiyeva,Kuralay K, AU - Nemr,Rita, AU - Echtay,Akram, AU - Racoubian,Eddie, AU - Sarray,Sameh, AU - Almawi,Wassim Y, Y1 - 2019/07/26/ PY - 2019/06/04/received PY - 2019/07/12/revised PY - 2019/07/24/accepted PY - 2019/7/30/pubmed PY - 2019/8/28/medline PY - 2019/7/30/entrez KW - Apolipoprotein E KW - Diabetic nephropathy KW - Genotyping KW - Type 2 diabetes mellitus SP - 144011 EP - 144011 JF - Gene JO - Gene VL - 715 N2 - BACKGROUND: An association between Apolipoprotein E (Apo E) alleles and genotypes and diabetic nephropathy (DN) was suggested, but with inconsistent results. We tested the relationship between serum lipids, Apo E alleles and genotypes with type 2 diabetes (T2DM), and DN pathogenesis. METHODS: Study subjects comprised 1389 normoglycemic controls, and 1422 T2DM patients, of whom 825 were normoalbuminuric (DWN), and 597 presented with nephropathy (DN). RESULTS: Significantly lower Apo ε2, and higher Apo ε4 allele frequencies was seen among T2DM patients than controls. Significantly higher frequency of ε3/ε4, and lower frequencies of ε3/ε3, ε2/ε3, and ε4/ε4 carriers was seen among T2DM cases. Apo ε2-carrying individuals were more frequently found in controls than in patients, while significantly higher frequency of ε4-carrying genotypes was seen in T2DM cases. Significantly higher ε2, and lower ε3 allele frequencies were noted for DN group compared to DWN group. Significantly higher frequency of ε2-containing ε2/ε3 and ε2/ε4, and lower frequencies of ε3/ε3 carriers was seen among DN cases. Apo ε3/ε3 was associated with higher total cholesterol, LDL-cholesterol, and triglyceride levels in DN patients, and significantly higher triglyceride levels were seen in ε2/ε3-carrying DN patients. Logistic regression analysis confirmed the association of Apo ε3-containing ε3/ε3, ε2/ε3, and ε3/ε4, and Apo ε2-containing ε2/ε4 with DN, after controlling for key covariates. CONCLUSION: The results of this case-control study provide evidence that the ε2 and ε3 alleles of APOE modify lipid profile, and constitute independent risk factors of DN in type 2 diabetes. The molecular mechanisms underlying this risk is discussed. SN - 1879-0038 UR - https://www.unboundmedicine.com/medline/citation/31357022/Apolipoprotein_E_genetic_polymorphism_influence_the_susceptibility_to_nephropathy_in_type_2_diabetes_patients_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-1119(19)30670-5 DB - PRIME DP - Unbound Medicine ER -