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Apolipoprotein E genetic polymorphism, remnant lipoproteins, and nephropathy in type 2 diabetic patients.
Am J Kidney Dis. 2002 Aug; 40(2):243-51.AJ

Abstract

BACKGROUND

We previously showed that the apolipoprotein (apo) Eepsilon2 allele is associated with the progression of diabetic nephropathy. The aim of the present study is to further investigate the association between apo E genetic polymorphism, plasma lipid levels (particularly remnant lipoproteins), and diabetic nephropathy.

SUBJECTS AND METHODS

One hundred fifty-eight patients with type 2 diabetes who had a duration of diabetes longer than 10 years were divided into the three apo E groups: apo E2 (n = 22), E3/3 (n = 102), and E4 (n = 34). Plasma levels of lipids and remnant lipoproteins were measured. The effect of apo E2 triglyceride (TG)-rich lipoproteins, including remnant lipoproteins, on the accumulation of cholesteryl esters by human mesangial cells (HMCs) was estimated by measuring the stimulation of radioactive carbon-labeled oleate incorporation into cholesteryl esters.

RESULTS

The frequency of overt nephropathy was significantly greater in apo E2 patients with diabetes (59.1%) than apo E3/3 (34.3%) or apo E4 patients (8.8%), and the frequency of normoalbuminuria was significantly greater in apo E4 patients with diabetes (67.6%) than apo E3/3 (34.3%) or apo E2 patients (4.5%). Logistical regression analysis showed that odds ratios of apo E2 and apo E4 genotypes for the presence of overt nephropathy were 10.179 (P = 0.0349) and 0.129 (P = 0.0028), respectively. Plasma TG and remnant-like lipoprotein particle cholesterol levels were significantly greater in apo E2 patients and significantly lower in apo E4 patients than apo E3/3 patients. Apo E2 TG-rich lipoproteins stimulated the accumulation of cholesteryl esters by HMCs significantly more than apo E3/3 or apo E4 TG-rich lipoproteins.

CONCLUSION

Apo E2 is a positive factor and apo E4 is a negative factor for diabetic nephropathy. Apo E2 TG-rich lipoproteins, including remnant lipoproteins, affected HMCs. Remnant lipoproteins may have an important role in the progression of diabetic nephropathy.

Authors+Show Affiliations

Department of Medicine, Diabetes and Endocrine Division, Kawasaki Medical School, Kurashiki, Japan. eto@med.kawasaki-m.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12148096

Citation

Eto, Masaaki, et al. "Apolipoprotein E Genetic Polymorphism, Remnant Lipoproteins, and Nephropathy in Type 2 Diabetic Patients." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, vol. 40, no. 2, 2002, pp. 243-51.
Eto M, Saito M, Okada M, et al. Apolipoprotein E genetic polymorphism, remnant lipoproteins, and nephropathy in type 2 diabetic patients. Am J Kidney Dis. 2002;40(2):243-51.
Eto, M., Saito, M., Okada, M., Kume, Y., Kawasaki, F., Matsuda, M., Yoneda, M., Matsuki, M., Takigami, S., & Kaku, K. (2002). Apolipoprotein E genetic polymorphism, remnant lipoproteins, and nephropathy in type 2 diabetic patients. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 40(2), 243-51.
Eto M, et al. Apolipoprotein E Genetic Polymorphism, Remnant Lipoproteins, and Nephropathy in Type 2 Diabetic Patients. Am J Kidney Dis. 2002;40(2):243-51. PubMed PMID: 12148096.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Apolipoprotein E genetic polymorphism, remnant lipoproteins, and nephropathy in type 2 diabetic patients. AU - Eto,Masaaki, AU - Saito,Mieko, AU - Okada,Mizuho, AU - Kume,Yoshie, AU - Kawasaki,Fumiko, AU - Matsuda,Masafumi, AU - Yoneda,Masaya, AU - Matsuki,Michihiro, AU - Takigami,Shigeru, AU - Kaku,Kohei, PY - 2002/7/31/pubmed PY - 2002/8/13/medline PY - 2002/7/31/entrez SP - 243 EP - 51 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am J Kidney Dis VL - 40 IS - 2 N2 - BACKGROUND: We previously showed that the apolipoprotein (apo) Eepsilon2 allele is associated with the progression of diabetic nephropathy. The aim of the present study is to further investigate the association between apo E genetic polymorphism, plasma lipid levels (particularly remnant lipoproteins), and diabetic nephropathy. SUBJECTS AND METHODS: One hundred fifty-eight patients with type 2 diabetes who had a duration of diabetes longer than 10 years were divided into the three apo E groups: apo E2 (n = 22), E3/3 (n = 102), and E4 (n = 34). Plasma levels of lipids and remnant lipoproteins were measured. The effect of apo E2 triglyceride (TG)-rich lipoproteins, including remnant lipoproteins, on the accumulation of cholesteryl esters by human mesangial cells (HMCs) was estimated by measuring the stimulation of radioactive carbon-labeled oleate incorporation into cholesteryl esters. RESULTS: The frequency of overt nephropathy was significantly greater in apo E2 patients with diabetes (59.1%) than apo E3/3 (34.3%) or apo E4 patients (8.8%), and the frequency of normoalbuminuria was significantly greater in apo E4 patients with diabetes (67.6%) than apo E3/3 (34.3%) or apo E2 patients (4.5%). Logistical regression analysis showed that odds ratios of apo E2 and apo E4 genotypes for the presence of overt nephropathy were 10.179 (P = 0.0349) and 0.129 (P = 0.0028), respectively. Plasma TG and remnant-like lipoprotein particle cholesterol levels were significantly greater in apo E2 patients and significantly lower in apo E4 patients than apo E3/3 patients. Apo E2 TG-rich lipoproteins stimulated the accumulation of cholesteryl esters by HMCs significantly more than apo E3/3 or apo E4 TG-rich lipoproteins. CONCLUSION: Apo E2 is a positive factor and apo E4 is a negative factor for diabetic nephropathy. Apo E2 TG-rich lipoproteins, including remnant lipoproteins, affected HMCs. Remnant lipoproteins may have an important role in the progression of diabetic nephropathy. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/12148096/Apolipoprotein_E_genetic_polymorphism_remnant_lipoproteins_and_nephropathy_in_type_2_diabetic_patients_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0272-6386(02)00037-9 DB - PRIME DP - Unbound Medicine ER -