Insulin-like growth factor I promoter polymorphism, risk of stroke, and survival after stroke: The Rotterdam study

Background and purpose: Low levels of insulin-like growth factor I (IGF-I) predispose to atherosclerosis and may therefore increase the risk of stroke. Low levels have also been found to influence the outcome of cardiovascular and cerebrovascular disease. A polymorphism in the promoter region of the IGF-I gene influences IGF-I levels. Non-carriers of the 192 bp allele have lower levels of IGF-I compared with 192 bp allele carriers. We studied the IGF-I polymorphism in relation to the risk of stroke and survival after stroke. Methods: We studied 6808 subjects of the Rotterdam Study, who were followed for the occurrence of stroke and death after stroke. Subjects were grouped according to the 192 bp allele of IGF-I into non-carriers, heterozygotes, and homozygotes. The risk of stroke and survival after stroke was studied using Cox regression analysis, adjusting for age and sex, with homozygotes for the wildtype allele as the reference. Results: Non-carriers had a relative risk of 0.8 (95% Cl: 0.6 to 1.0) for the occurrence of any stroke and 0.7 (95% Cl: 0.5 to 1.0) for ischaemic stroke. For non-carriers, the relative risk of death after any stroke was 1.5 (95% Cl: 1.0 to 2.2). After an ischaemic stroke, this relative risk was 1.5 (95% Cl: 0.9 to 2.6) and after a haemorrhagic stroke 5.2 (95% Cl: 1.3 to 21.5). Conclusions: Our study suggests that IGF-I is a significant determinant of survival after stroke.