title: A founder haplotype of APOE-Sendai mutation associated with lipoprotein glomerulopathy.
abstract: Lipoprotein glomerulopathy (LPG) is a hereditary disease characterized by lipoprotein thrombi in the glomerulus, hyperlipoproteinemia, and a marked increase in serum apolipoprotein E (APOE). More than 12 APOE mutations have been identified as causes of LPG, and APOE-Sendai (Arg145Pro) mutation was frequently detected in patients from the eastern part of Japan including Yamagata prefecture. Recently, effective therapy with intensive lipid-lowering agents was established, and epidemiologic data are required for early diagnosis. We determined the haplotype structure of APOE-Sendai in 13 patients from 9 unrelated families with LPG, and found that the haplotype of all APOE-Sendai mutations was identical, suggesting that APOE-Sendai mutation is common in Japanese patients probably through a founder effect. We also studied the gene frequency of APOE-Sendai in 2023 control subjects and 418 patients receiving hemodialysis in Yamagata prefecture using the TaqMan method, but did not identify any subjects carrying the mutation, indicating that it is very rare in the general population even in the eastern part of Japan. In addition to APOE mutation, other genetic and/or epigenetic factors are considered to be involved in the pathogenesis of LPG because of its low penetrance. The patients did not have a common haplotype of the counterpart APOE allele, and some patients had the same haplotype of the counterpart APOE allele as the asymptomatic carriers. These results suggest that the counterpart APOE allele is not likely associated with the onset of LPG. Further study is required to clarify the pathogenesis of LPG.
authors: Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan.
authors: Kentaro
authors: K
authors: Toyota
authors: Taeko
authors: T
authors: Hashimoto
authors: Daisuke
authors: D
authors: Ogino
authors: Akira
authors: A
authors: Matsunaga
authors: Minoru
authors: M
authors: Ito
authors: Ikuto
authors: I
authors: Masakane
authors: Noriyuki
authors: N
authors: Degawa
authors: Hiroshi
authors: H
authors: Sato
authors: Sayuri
authors: S
authors: Shirai
authors: Kazuo
authors: K
authors: Umetsu
authors: Gen
authors: G
authors: Tamiya
authors: Takao
authors: T
authors: Saito
authors: Kiyoshi
authors: K
authors: Hayasaka
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D023061:Gene Order; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007564:Japan; D007674:Kidney Diseases / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D006435:Renal Dialysis; D055815:Young Adult
chemical_list: D001057:Apolipoproteins E