Genetic evaluation of lipoprotein(a) in intracranial aneurysm disease

Elevations in serum lipoprotein(a) [Lp(a)] levels have been reported in intracranial aneurysm (IA) disease. Our aim was to investigate a genetic basis for this observation.

We performed a comparative analysis of size polymorphisms at two loci (kringle 4 [K4] and TTTTA pentanucleotide [PN] repeats) within the apolipoprotein(a) gene on Chromosome 6q26-27 among patients with sporadic IAs (n = 50), members of three IA families (n = 50), and control subjects (n = 50).

There was no significant difference in mean Lp(a) levels between patients with sporadic IAs and control subjects, but IA family members exhibited a more than twofold elevation in mean Lp(a) levels, compared with control subjects (29.2 versus 12.9 mg %). Inverse relationships between K4/PN numbers and serum Lp(a) levels were demonstrated; genotype frequencies did not differ significantly from a Hardy-Weinberg equilibrium or from published frequencies for other Caucasian populations. We detected no difference in mean K4 and PN genotypic indices between patients with IAs and control subjects (9.3 and 16.92 versus 9.0 and 16.92, respectively), but IA families did exhibit a lower mean K4 genotypic index (7.7), compared with control subjects. Superficial analysis of family pedigrees revealed no suggestion of linkage between K4/PN genotypes and IA disease.

The previously described elevation in Lp(a) levels among patients with sporadic IAs might be explained by an acute-phase response. Crude Lp(a) measurements might provide a useful predictive test for familial IA disease, but with the disadvantage of low specificity. The possibility of linkage of familial IA disease to a particular apolipoprotein(a) isoform size range has not been eliminated.