Association of a novel 3-amino acid deletion mutation of apolipoprotein E (Apo E Tokyo) with lipoprotein glomerulopathy

Citation
K. Konishi et al., Association of a novel 3-amino acid deletion mutation of apolipoprotein E (Apo E Tokyo) with lipoprotein glomerulopathy, NEPHRON, 83(3), 1999, pp. 214-218
Citations number
15
Categorie Soggetti
Urology & Nephrology","da verificare
Journal title
NEPHRON
ISSN journal
00282766 → ACNP
Volume
83
Issue
3
Year of publication
1999
Pages
214 - 218
Database
ISI
SICI code
0028-2766(199911)83:3<214:AOAN3A>2.0.ZU;2-Y
Abstract
Lipoprotein glomerulopathy (LPG) is a newly recognized renal disease charac terized by abnormal lipoprotein deposition in the glomeruli, dysbetalipopro teinemia, and a high level of plasma apolipoprotein (apo) E. We identified a novel apo E mutation in a 56-year-old Japanese male with LPG. Although th e plasma cholesterol and triglyceride levels were normal, the levels of int ermediate-density lipoprotein cholesterol and apo E were elevated to 13 mg/ dl (0.336 mmol/l; 4.2+/-2.9 mg/dl, mean +/- SD, in 12 normolipidemic contro ls) and 9.2 mg/dl, respectively. Biochemical analysis revealed an unusual a po E phenotype (E1/3), Apo E genotyping using DNA digested by a restriction enzyme (Hhal) identified a 66-bp fragment which was not seen with any of t he common alleles. Sequence analysis of the amplified genomic DNA fragments showed a 9-bp deletion in exon 4 of the apo E gene resulting in a 3-amino acid deletion (residues 141-143). This novel mutation involves the region o f the apo E molecule known to be critically involved in binding to its rece ptor, and this may well transform the apo E molecule, an inefficient ligand , to its receptor(s). How this mutations causes glomerular damage remains t o be determined.