The apo(a) gene (TTTTA)n promoter polymorphism and its association with variability in exons of the kringle IV types 8 to 10

BackgroundA 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.MethodsWe 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 TTTTAn 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.ResultsOverall 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 TTTTAn repetition was in allelic association with all five tested polymorphic loci (P < 0.0023).ConclusionsThe sequence variants from the coding portion of kringle IV types 8–10 of the LPA locus are significantly associated with the TTTTAn repetition but still are not able to markedly account for the TTTTAn locus effect.