Genetic predictors for stroke in children with sickle cell anemia

Blood. 2011 Jun 16;117(24):6681-4. doi: 10.1182/blood-2011-01-332205. Epub 2011 Apr 22.


Stroke is a devastating complication of sickle cell anemia (SCA), affecting 5% to 10% of patients before adulthood. Several candidate genetic polymorphisms have been proposed to affect stroke risk, but few have been validated, mainly because previous studies were hampered by relatively small sample sizes and the absence of additional patient cohorts for validation testing. To verify the accuracy of proposed genetic modifiers influencing stroke risk in SCA, we performed genotyping for 38 published single nucleotide polymorphisms (SNPs), as well as α-thalassemia, G6PD A(-) variant deficiency, and β-globin haplotype in 2 cohorts of children with well-defined stroke phenotypes (130 stroke, 103 nonstroke). Five polymorphisms had significant influence (P < .05): SNPs in the ANXA2, TGFBR3, and TEK genes were associated with increased stroke risk, whereas α-thalassemia and a SNP in the ADCY9 gene were linked with decreased stroke risk. Further investigation at these genetic regions may help define mutations that confer stroke risk or protection in children with SCA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anemia, Sickle Cell / complications
  • Anemia, Sickle Cell / diagnosis
  • Anemia, Sickle Cell / genetics*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • Genetic Markers* / physiology
  • Genetic Predisposition to Disease*
  • Glucosephosphate Dehydrogenase / genetics
  • Glucosephosphate Dehydrogenase Deficiency / complications
  • Glucosephosphate Dehydrogenase Deficiency / diagnosis
  • Glucosephosphate Dehydrogenase Deficiency / genetics
  • Humans
  • Male
  • Polymorphism, Single Nucleotide / physiology
  • Risk Factors
  • Stroke / diagnosis
  • Stroke / etiology
  • Stroke / genetics*
  • beta-Globins / genetics


  • Genetic Markers
  • beta-Globins
  • Glucosephosphate Dehydrogenase
  • glucose-6-phosphate dehydrogenase A-