A novel 18-amino acid deletion in apolipoprotein E associated with lipoprotein glomerulopathy

Background. Lipoprotein glomerulopathy (LPG) is a novel disease characteriz ed by proteinuria, lipoprotein thrombi in glomeruli, and an increased conce ntration of plasma apolipoprotein (apo) E. Previous studies have shown that a genetic disorder of apo E may be associated with the genesis of this dis ease. Methods. An apo E mutation was analyzed in a 57-year-old Japanese male with LPG and systemic atherosclerotic complications. Apo E phenotypes were anal yzed by isoelectric focusing and immunoblotting. Apo E genotypes were deter mined by restriction fragment isotyping with HhaI. Polymerase chain reactio n (PCR) products of apo E coding region exons 3 and 4 were cloned into pT7B lue-T-vector and were sequenced. Results. A novel apo E mutation was identified in this patient and his fami ly. There was a discrepancy between an apo E phenotype (E1/3) and genotype (E3/3). Sequence analysis showed a 54 bp deletion in exon 4 of the apo E ge ne, causing the Is-amino acid deletion (Gln 156-Gly 173-->0). This deletion mutation was further confirmed by the detection of a short fragment of PCR -amplified DNA using polyacrylamide gel electrophoresis. The patient was a heterozygote with apo El, and this mutation was determined to be the struct ural basis for the apo El phenotype. One of two daughters was a heterozygou s carrier of apo El, although she did not have proteinuria or atherosclerot ic diseases. Conclusions. Apo El (Gln 156-Gly 173-->0) is a novel mutation of apo E that may be etiologically related to LPG and to the development of atherosclero sis. The result of this family study suggests that the occurrence of LPG ma y involve other genetic or environmental factors.