The apo(a) gene (TTTTA)n promoter polymorphism and its association with variability in exons of the kringle IV types 8 to 10.
BACKGROUND
A large portion of lipoprotein (a) concentration is explained by the variable number of kringle domains at the apo(a) gene. The (TTTTA)(n) repetition from the promoter of the apo(a) gene is supposed to be a relevant candidate for the additional regulation of lipoprotein (a) levels.


METHODS
We scanned the kringle IV types 8-10 of the apo(a) gene for candidate variants that could be at least partly responsible for the (TTTTA)(n) repetition effect. The selected sample group comprises of 160 unrelated individuals designed to cover a representative amount even of the rare TTTTA(n) allele carriers. The high resolution melting method was used to scan exons of selected kringles for alteration. Linkage disequilibrium and haplotype frequencies were assigned using Arlequine software.


RESULTS
Overall eight different sequence variants were detected from which all but two were rare (c.66A-->C; c.74C-->T; c.133G-->A; c.154C-->T;+1G-->A 5'splice site; c.16G-->T; c.61G-->A; c.63C-->T). However the TTTTA(n) repetition was in allelic association with all five tested polymorphic loci (P<0.0023).


CONCLUSIONS
The sequence variants from the coding portion of kringle IV types 8-10 of the LPA locus are significantly associated with the TTTTA(n) repetition but still are not able to markedly account for the TTTTA(n) locus effect.
Hirschfeldova
Katerina
K
Institute of Biology and Medical Genetics, 1st Faculty of Medicine and General Teaching Hospital in Prague, Charles University, Prague, 12800, Czech Republic. kzidk@lf1.cuni.cz
Lipovska
Dana
D
Skrha
Pavel
P
Ceska
Richard
R
D001054:Apolipoproteins A / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D005091:Exons / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D018082:Kringles; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*
D001054:Apolipoproteins A