Genetic evaluation of lipoprotein(a) in intracranial aneurysm disease

OBJECTIVE: Elevations in serum lipoprotein(a) [Lp(a)] levels have been repo rted in intracranial aneurysm (IA) disease. Our aim was to investigate a ge netic basis for this observation. METHODS: We performed a comparative analysis of size polymorphisms at two l oci (kringle 4 [K4] and TTTTA pentanucleotide [PN] repeats) within the apol ipoprotein(a) gene on Chromosome 6q26-27 among patients with sporadic IAs ( n = 50), members of three IA families (n = 50), and control subjects (n = 5 0). RESULTS: There was no significant difference in mean Lp(a) levels between p atients with sporadic IAs and control subjects, but IA family members exhib ited a more than twofold elevation in mean Lp(a) levels, compared with cont rol subjects (29.2 versus 12.9 mg %). Inverse relationships between K4/PN n umbers and serum Lp(a) levels were demonstrated; genotype frequencies did n ot 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 subj ects (9.3 and 16.92 versus 9.0 and 16.92, respectively), but IA families di d exhibit a lower mean K4 genotypic index (7.7), compared with control subj ects. Superficial analysis of family pedigrees revealed no suggestion of li nkage between K4/PN genotypes and IA disease. CONCLUSION: The previously described elevation in Lp(a) levels among patien ts with sporadic IAs might be explained by an acute-phase response. Crude L p(a) measurements might provide a useful predictive test for familial IA di sease, but with the disadvantage of tow specificity. The possibility of lin kage of familial IA disease to a particular apolipoprotein(a) isoform size range has not been eliminated.