| Project/Area Number |
12671128
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | KAWASAKI MEDICAL SCHOOL |
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Principal Investigator |
ETO Masaaki Kawasaki Medical School,Department of Medicine,Associate professor, 医学部, 助教授 (90133818)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | apolipoprotein E / diabetic nephropathy / remant lipoproteins / mesangial cells / apolipoprotein E2 / トリグリセライド / メサンギウム細胞 / PKC活性 / ヒトメサンギウム細胞 / RLP / 遺伝子 |
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| Research Abstract |
Previously we demonstrated that the apolipoprotein (apo) E e2 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 remnant lipoproteins and diabetic nephropathy. One hundred and fifty eight type 2 diabetic patients who had a diabetes duration over 10 years were divided into the 3 apo E groups ; apo E2, E3/3 and E4.Plasma levels of lipids and remnant lipoproteins were measured.The effect of apo E2 triglyceride (TG)-rich lipoproteins including remnant lipoproteins on accumulation of cholesteryl esters by human mesangial cells (HMCs) was estimated by measurement of the stimulation of 14C-oleate incorporation into cholesteryl esters. The frequency of overt nephropathy was significant^ higher in apo E2 diabetic patients (59.1%) than in apo E3/3 (34.3%) or apo E4 patients (8 8%) and the frequency of normoalbuminuria was significantly higher in apo E4 diabetic patients (67 6%) than in 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=00349) and 0.129 (p=0.0028), respectively. Plasma levels of triglyceride and remnant-like lipoprotein particles (RLP)-chol and were significantly higher in apo E2 patients, and significantly lower, n apo E4 patients than in apo E3/3 patients. Apo E2 TG-rich lipoproteins stimulated accumulate of cholesteryl esters by HMCs significantly more than apo E3/3 or apo E4 TG-rich lipoproteins. Apo E2, s a positive genetic factor and apo E4 is a negative genetic factor for diabetic nephropathy. Apo E2 TG-rich lipoproteins were uptaken more avidly by HMCs. Remnant lipoproteins may have an important role in the progression of diabetic nephropathy.
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