Identification of a founder haplotype of APOE-Kyoto variant in lipoprotein glomerulopathy

Background Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant inherited kidney disease with incomplete penetrance, characterized by nephrotic-range proteinuria, hypertriglyceridemia, and progressive renal dysfunction with elevated serum apoE level. More than fifteen APOE mutations have been associated with LPG, with APOE Kyoto (Arg43Cys) the leading mutation in about 200 patients. We previously observed clustering of APOE Kyoto-causing LPG in a Han population in China. We now explore the haplotype of the APOE Kyoto heterozygotes and the distribution of LPG patients in China. Methods 115 APOE Kyoto heterozygotes were enrolled and identified by Sanger sequencing, and in this study, the haplotypes of Kyoto and counterpart alleles were investigated by TA cloning and Sanger sequencing. Results 114 out of 115 APOE Kyoto alleles shared an identical haplotype, likely from haplotype 1 inε3. Among heterozygotes, the counterpart of APOE Kyoto allele showed haplotype diversity, and the difference in haplotype distribution of the counterpart allele was not observed between LPG patients and asymptomatic carriers. Conclusions This study provides further evidence for the founder effect of APOE Kyoto may play a critical role in the progression of LPG.