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.
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Genetic drift and population-specific factors may influence the prevalence and clinical presentation of lipoprotein glomerulopathy.
“These variants exhibit distinct geographical distributions and founder effects, suggesting that genetic drift and population-specific factors may influence the prevalence and clinical presentation.[3,4]”
From Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy (2026) · cites this paper as [4]
APOE variants linked to lipoprotein glomerulopathy exhibit distinct geographical distributions and founder effects.
“These variants exhibit distinct geographical distributions and founder effects, suggesting that genetic drift and population-specific factors may influence the prevalence and clinical presentation.[3,4]”
From Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy (2026) · cites this paper as [4]
APOE Sendai (Arg145Pro) was observed mainly in central and northern Japan, especially in Yamagata and Miyagi, but not in China.
“APOE Sendai (Arg145Pro) was observed mainly in central and northern Japan, especially in Yamagata and Miyagi, but not in China71, 93).”
From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [93]
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- Authors
- Toyota, K., Hashimoto, T., Ogino, D., Matsunaga, A., Ito, M., Masakane, I., Degawa, N., Sato, H., Shirai, S., Umetsu, K., Tamiya, G., Saito, T., & Hayasaka, K.
- Affiliations
- Yamagata University (JP)
- Yamagata City Hospital Saiseikan (JP)
- Tohoku University (JP)
- St. Marianna University School of Medicine (JP)
- Fukuoka University (JP)
- Corresponding author
- Hayasaka, Kiyoshi
- ORCID
- Venue
- Journal of Human Genetics
- Published
- 2013-02-14
- Volume
- 58
- Issue
- 5
- Pages
- 254-258
- ISSN
- 1434-5161 (ISSN-L)
- 1435-232X
- OpenAlex
- W2060080246
- Cited by
- 19
- References
- 24
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2022: 4 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 2 · 2014: 3 · 2013: 2
- FWCI
- 1.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Human Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Fukuoka University
- Japan Society for the Promotion of Science (23791149)
- Topics
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- lipoprotein glomerulopathy, apolipoprotein E, founder effect, founder haplotype, hyperlipoproteinemia, lipid-lowering therapy, hemodialysis patients, Yamagata Prefecture, genetic disorders
- MeSH terms
- Adolescent, Adult, Aged, Apolipoproteins E, Child, DNA Mutational Analysis, Female, Haplotypes, Renal Dialysis, Humans, Japan, Kidney Diseases, Male, Middle Aged, Mutation, Pedigree, Founder Effect, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Gene Order, Young Adult
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