Pentanucleotide repeat and size polymorphisms in the apolipoprotein(a) gene are associated with the lipoprotein(a) concentration in chronic hemodialysis patients.
The elevation of serum or plasma lipoprotein(a) [Lp(a)] levels is regarded as an independent risk factor for cardiovascular disease, and many previous reports demonstrated that Lp(a) levels in hemodialysis patients were significantly higher than in controls. The purpose of this study was to investigate the effect of a pentanucleotide repeat polymorphism [(TTTTA)n] in the 5'-flanking region of the apolipoprotein(a) [apo(a)] gene and of a size polymorphism of apo(a) for elevated Lp(a) concentrations observed in chronic hemodialysis patients. We studied 172 patients on chronic hemodialysis and 199 healthy adults. For analysis of the pentanucleotide repeat polymorphism, polymerase chain reaction products were loaded on polyacrylamide gel for electrophoresis. apo(a) size phenotyping was performed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. The median level of Lp(a) in the patients was 14.2 mg/dl which was significantly higher than that in controls (12.0 mg/dl; p < 0.05). In the genotype of (TTTTA)8/8, the median Lp(a) level in the patients (15.9 mg/dl) was significantly higher than that in controls (13.0 mg/dl; p < 0.05). In the genotype of (TTTTA)8/8 with large-sized apo(a) isoforms (A16-A25), the patients had significantly higher Lp(a) levels than the controls (p < 0.05). In conclusion, increased Lp(a) levels in chronic hemodialysis patients were mainly attributed to the combination of eight repeats of the pentanucleotide polymorphism and large-sized isoforms of apo(a).
Tanaka
M
M
Institute of Community Medicine, University of Tsukuba, Tsukuba, Japan.
Yanagi
H
H
Ando
R
R
Kurihara
S
S
Hirano
C
C
Kobayashi
K
K
Kikuchi
S
S
Hamaguchi
H
H
Tsuchiya
S
S
Tomura
S
S
D001054:Apolipoproteins A / Q000235:genetics*; D002908:Chronic Disease; D005260:Female; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D006435:Renal Dialysis; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*
D001054:Apolipoproteins A; D017270:Lipoprotein(a)