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.