Elevated levels of
lipoprotein(a) has been regarded as an independent risk factor for coronary, peripheral and
cerebral atherosclerosis. The enormous intra-personal variation in the plasma concentration of
lipoprotein(a) is almost entirely controlled by the
apolipoprotein(a) i.e. gene locus on the chromosome 6q 26-27. The
apolipoprotein(a) molecule is highly polymorphic and is known to exist in multiple, genetically determined
isoforms. These polymorphisms may be responsible for difference in promoter activity, variable size of
apolipoprotein(a) and thereby variation in plasma
lipoprotein(a) concentration. We studied the effect of two types of polymorphisms, (i) variation in length of the pentanucleotide repeat in the 5' flanking region starting -1373 bp upstream of AUG
codon, and (ii) the Kringle-4 type 2 size polymorphism, on plasma
lipoprotein(a) levels in North Indian population. The study group consisted of 88 angiographically assessed male
coronary artery disease patients (age range 30-70 years) and 83 age- and sex-matched healthy controls. The pentanucleotide repeat polymorphism was analysed using polymerase chain reaction. In all, 8/11 pentanucleotide repeat
isoforms were observed. Using SDS-
agarose gel electrophoresis and immunoblotting
isoforms having 12-50 Kringle-4 type 2 repeats were detected. Our study indicates a strong association of elevated plasma
lipoprotein(a) concentration with
coronary artery disease. An inverse correlation was seen between
lipoprotein concentration and
isoform size for both the pentanucleotide repeat polymorphism and the Kringle-4 type 2 polymorphisms; statistically significant difference (p = 0.001) was, however, observed only for the later.