Endoglin gene polymorphism as a risk factor for sporadic intracerebral hemorrhage

Intracerebral hemorrhage (ICH) is a common and serious type of stroke. Recent studies have shown that inherited factors that affect the development of the vessel wall can increase the risk of ICH. We studied endoglin as a candidate gene in patients with sporadic ICH, since mutations in this gene can cause telangiectasia formation. One hundred three patients with sporadic ICH and 202 controls were studied. The polymerase chain reaction and single-strand conformational polymorphism analysis were used to screen for mutations in exon 7 of the endoglin gene. No coding mutations in exon 7 were identified in the ICH patients or controls. A 6-base intronic insertion was found 26 bases beyond the 3' end of exon 7. The homozygous form of the insertion was present in 9 of 103 (8.7%) ICH patients compared with 4 of 202 (2.0%) controls, p = 0.012 (odds ratio 4.8 [95% confidence interval, 1.28, 21.60]). Analysis of the endoglin transcript around the insertion did not reveal any changes in the RNA sequence. There were no obvious clinical features that distinguished the ICH patients with the homozygous insertion from the other patients. The pathophysiologic mechanism underlying this association remains to be determined.