Human Molecular Genetics, Vol 6, 1099-1107, Copyright © 1997 by Oxford University Press
LH Puckey, RM Lawn and BL Knight
Genotypes at five previously described polymorphic sites at the
apolipoprotein(a) gene locus have been determined for the members of 27
families as well as for unrelated white Caucasian and Asian-Indian
subjects, and their relationship with isoform size and plasma
lipoprotein(a) concentrations investigated. There was strong linkage
disequilibrium between sites at the 5'-region of the gene and also between
this region and a site in the coding sequence for Kringle 4-37 on the other
side of the polymorphic Kringle 4 repeat region. There was no evidence that
changes at any of the sites had any direct effect upon lipoprotein(a)
concentration. However, certain haplotypes were present almost exclusively
on apolipoprotein(a) alleles within a restricted range of sizes and
associated lipoprotein(a) concentrations. After correcting for the effect
of allele size, there were clear differences between the lipoprotein(a)
concentrations associated with alleles of different haplotypes, suggesting
that there may be genetically distinct groups of apolipoprotein alleles of
different size and different levels of expression. Factors that regulate
expression apparently exchange at a rate similar to the rate of change of
Kringle 4 repeat number.
ARTICLES
Polymorphisms in the apolipoprotein(a) gene and their relationship to allele size and plasma lipoprotein(a) concentration
MRC Lipoprotein Team, Clinical Sciences Centre, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
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