PMID- 10432380
OWN - NLM
STAT- MEDLINE
DCOM- 19990830
LR  - 20211203
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 56
IP  - 2
DP  - 1999 Aug
TI  - A novel apolipoprotein E mutation, E2 (Arg25Cys), in lipoprotein glomerulopathy.
PG  - 421-7
AB  - BACKGROUND: Lipoprotein glomerulopathy (LPG) is characterized by intraglomerular 
      lipoprotein thrombosis and high plasma concentrations of apolipoprotein (apo) E. 
      An apo E variant, apo E2 (Arg145Pro) Sendai, was recently identified in three
      patients with LPG. We detected a novel point mutation in the apo E gene in a
      patient with LPG, and we characterized the mutant apo E. METHODS: The propositus 
      was a 32-year-old male patient on maintenance hemodialysis because of LPG. The
      mutation was detected by sequencing of genomic DNA from the patient and was
      confirmed by restriction fragment length polymorphism (RFLP) with Aor51HI.
      Recombinant apo E2 (Arg25Cys) Kyoto and normal apo E3 were expressed from COS-1
      cells. Low-density lipoprotein (LDL) receptor-binding activities of the variants 
      were determined in an in vitro competition assay. RESULTS: The propositus had the
      apo E phenotype E2/E4, as determined by isoelectric focusing, and the genotype
      epsilon3/epsilon4, as determined by RFLP with HhaI. Sequence analysis of
      amplified DNA showed a C to T transition, changing the codon for residue 25 from 
      arginine to cysteine. The proband was a heterozygous carrier for apo E2
      (Arg25Cys) Kyoto. A family study showed that the mother was a heterozygous
      carrier of apo E2 Kyoto and had dysbetalipoproteinemia, but no LPG. The
      pathophysiological effect of this mutation was investigated in vitro by binding
      studies of recombinant apo E2 Kyoto to LDL receptors on human fibroblasts. The
      ability of recombinant apo E2 Kyoto to displace LDL was reduced to 10% compared
      with recombinant apo E3. CONCLUSIONS: Apo E2 (Arg25Cys) Kyoto is a novel mutation
      of apo E that is etiologically related to LPG. However, our case indicates that
      the development of LPG may involve other genetic or environmental factors.
      Furthermore, our data suggest that arginine-25 of apo E plays an important
      functional role by influencing the receptor-binding ability of apo E.
FAU - Matsunaga, A
AU  - Matsunaga A
AD  - Department of Internal Medicine, Fukuoka University, School of Medicine, Japan.
FAU - Sasaki, J
AU  - Sasaki J
FAU - Komatsu, T
AU  - Komatsu T
FAU - Kanatsu, K
AU  - Kanatsu K
FAU - Tsuji, E
AU  - Tsuji E
FAU - Moriyama, K
AU  - Moriyama K
FAU - Koga, T
AU  - Koga T
FAU - Arakawa, K
AU  - Arakawa K
FAU - Oikawa, S
AU  - Oikawa S
FAU - Saito, T
AU  - Saito T
FAU - Kita, T
AU  - Kita T
FAU - Doi, T
AU  - Doi T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Apolipoprotein E2)
RN  - 0 (Apolipoproteins E)
RN  - 0 (DNA Primers)
RN  - 0 (Indicators and Reagents)
RN  - 0 (Iodine Radioisotopes)
RN  - 0 (Receptors, LDL)
RN  - 94ZLA3W45F (Arginine)
RN  - K848JZ4886 (Cysteine)
RN  - U86ZGC74V5 (Dimyristoylphosphatidylcholine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Apolipoprotein E2
MH  - Apolipoproteins E/blood/*genetics
MH  - Arginine
MH  - Cysteine
MH  - DNA Mutational Analysis
MH  - DNA Primers
MH  - Dimyristoylphosphatidylcholine/metabolism/pharmacology
MH  - Ethnicity/genetics
MH  - Exons
MH  - Family Health
MH  - Female
MH  - Fibroblasts/metabolism
MH  - Genotype
MH  - Humans
MH  - Indicators and Reagents/metabolism/pharmacology
MH  - Iodine Radioisotopes
MH  - Japan
MH  - Kidney Diseases/*genetics/*pathology
MH  - Kidney Glomerulus/*pathology
MH  - Male
MH  - Middle Aged
MH  - Phenotype
MH  - *Point Mutation
MH  - Polymorphism, Restriction Fragment Length
MH  - Protein Binding/drug effects
MH  - Receptors, LDL/metabolism
MH  - Skin/cytology
EDAT- 1999/08/05 00:00
MHDA- 1999/08/05 00:01
CRDT- 1999/08/05 00:00
PHST- 1999/08/05 00:00 [pubmed]
PHST- 1999/08/05 00:01 [medline]
PHST- 1999/08/05 00:00 [entrez]
AID - S0085-2538(15)46311-2 [pii]
AID - 10.1046/j.1523-1755.1999.00572.x [doi]
PST - ppublish
SO  - Kidney Int. 1999 Aug;56(2):421-7. doi: 10.1046/j.1523-1755.1999.00572.x.