Polymorphism of the heme oxygenase-1 gene and cerebral aneurysms

Inflammation is thought to play an important role in intracranial aneurysm formation. Heme-oxygenase-1(HO-1) is a novel anti-inflammatory factor. A length polymorphic variant of the HO-1 gene promoter region, comprising (GT)n dinucleotide repeats, is associated with altered levels of gene transcription: long (= 36 GT) repeats are associated with decreased HO-1. We hypothesized that patients with aneurysmal subarachnoid haemorrhage were more likely to have long repeats than controls. Sixty-nine patients with aneurysms and 230 age-matched controls were genotyped, and allelic repeats were classed as <36 (short and medium repeats) and >36 (long repeats). Patients were more likely to have =36 repeats than controls (8 v. 4%, p = 0.037. Control patients without aneurysms were more likely to have short alleles. Thus, facilitated up-regulation of HO-1 may be a protective anti-inflammatory factor against the development of intracranial aneurysms, whilst a propensity to a more pro-inflammatory state may put individuals at risk. However, because of the relatively small sample size and modest statistical significance, the data must be interpreted with caution and the association needs to be confirmed in further samples.