gms | German Medical Science

Objective: Linkage studies have identified various genetic regions to be associated with the occurrence of intracranial aneurysms (IA). Among those, a region on the X-chromosome (Xp22) seems to be most promising as a female preponderance in IA is well known. We identified two candidate genes within this region, FIGF (c-Fos-Induced-Growth-Factor-Gene), a VEGF family member, and ACE2 (angiotensin converting-enzyme 2), which plays a key role in the renin-angiotensin system. Five frequent genetic variants within FIGF and four within ACE2 were analyzed in a case-control study in order to look for an association with the occurrence of IA.

Methods: DNA was isolated from peripheral blood. Genetic regions around the variants of interest in FIGF were PCR amplified and analyzed by automated sequencing (ABI 3730x). Variants within ACE2 were investigated by melting-curve analysis after real-time PCR. Genotypes and allele frequencies were determined and compared between cases and controls by calculating odds ratios and 95% confidence intervals. Haplotypes spanning both genomic regions were constructed.

Results: The study population comprised 160 patients, 56 male, 104 female, median age 52 and 54 years, respectively, and 160 anonymous controls. Deviation from Hardy-Weinberg equilibrium was found in one single case. Genotype frequencies were not different between cases and controls in any of the 9 variants. Haplotypes comprising variants of both genes were constructed. Again, no difference between cases and controls could be substantiated.

Conclusions: Although FIGF and ACE2 are both coding for potent vasoactive enzymes, and both genes are located in close vicinity on the X-chromosome within a region that has been linked to IA, frequent genetic variants within those genes are not associated with the occurrence of IA in our European population. Our results do not exclude that other less frequent variants within those genes might contribute to IA pathogenesis.