Genetic variation at the IGF1 locus shows association to post-stroke outcome and to circulating IGF-I.

European journal of endocrinology / European Federation of Endocrine Societies

PubMedID: 24005314

Aberg ND, Olsson S, Aberg D, Jood K, Stanne TM, Nilsson M, Blomstrand C, Svensson J, Isgaard J, Jern C. Genetic variation at the IGF1 locus shows association to post-stroke outcome and to circulating IGF-I. Eur J Endocrinol. 2013;.
OBJECTIVE
In humans, serum IGF-I (s-IGF-I) is associated with outcome after ischemic stroke (IS). Therefore variation at the IGF1 locus could also associate with both IS and s-IGF-I. We investigated whether genetic variation at the IGF1 locus is associated with 1) s-IGF-I, 2) IS occurrence 3) IS severity, and 4) post-stroke outcome.

DESIGN / METHODS
Patients (n=844; 66% males, mean age 56 years) and community controls (n = 668) were included from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Post-stroke outcome was evaluated with the modified Rankin Scale (mRS) at 3 months and 24 months after index stroke, and baseline stroke severity with the Scandinavian Stroke Scale (SSS). s-IGF-I was determined in patients and after random selection in 40 of the controls.

RESULTS
Eleven single nucleotide polymorphisms (SNPs) were selected in the IGF1 gene. In healthy controls the major allele of rs7136446 was associated with higher s-IGF-I, whereas in patients no such association was found. No SNP was associated with IS, nor with stroke severity. After multivariate correction for presence of diabetes, smoking and hypertension, the major allele of rs7136446 was associated with favorable functional outcome 24-month post-stroke (Odds ratio; OR 1.42, 95% confidence interval; CI 1.07-1.90).

CONCLUSION
Variation in rs7136446 of the IGF1 gene associates with post-stroke outcome in relatively young IS patients. Also, rs7136446 associates with s-IGF-I in controls but not in IS, which indicates that IS perturbs a normal genetic impact on s-IGF-I levels.