title: Genetic variation at the IGF1 locus shows association with post-stroke outcome and to circulating IGF1.
abstract: OBJECTIVE
  In humans, serum IGF1 (s-IGF1) is associated with outcome after ischemic stroke (IS). Therefore variation at the IGF1 locus could also associate with both IS and s-IGF1. We investigated whether genetic variation at the IGF1 locus is associated with i) s-IGF1, ii) IS occurrence, iii) IS severity, and iv) post-stroke outcome.
  
  
  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 at 3 and 24 months after index stroke, and baseline stroke severity with the Scandinavian Stroke Scale. s-IGF1 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-IGF1, 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-months post-stroke (odds ratio 1.46; 95% CI 1.09-1.96).
  
  
  CONCLUSIONS
  Variation in rs7136446 of the IGF1 gene associates with post-stroke outcome in relatively young IS patients. Also, rs7136446 associates with s-IGF1 in controls but not in IS, which indicates that IS perturbs a normal genetic impact on s-IGF1 levels.
authors.affiliation: Laboratory of Experimental Endocrinology, Department of Internal Medicine, The Sahlgrenska Academy, Sahlgrenska University Hospital.
authors.forename: N David
authors.initials: ND
authors.lastname: Aberg
authors.forename: Sandra
authors.initials: S
authors.lastname: Olsson
authors.forename: Daniel
authors.initials: D
authors.lastname: Aberg
authors.forename: Katarina
authors.initials: K
authors.lastname: Jood
authors.forename: Tara M
authors.initials: TM
authors.lastname: Stanne
authors.forename: Michael
authors.initials: M
authors.lastname: Nilsson
authors.forename: Christian
authors.initials: C
authors.lastname: Blomstrand
authors.forename: Johan
authors.initials: J
authors.lastname: Svensson
authors.forename: Jörgen
authors.initials: J
authors.lastname: Isgaard
authors.forename: Christina
authors.initials: C
authors.lastname: Jern
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D002545:Brain Ischemia / Q000150:complications*; D005260:Female; D005838:Genotype; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D020521:Stroke / Q000097:blood* / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D013548:Sweden / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D007334:Insulin-Like Growth Factor I