title: Gene interactions and stroke risk in children with sickle cell anemia.
abstract: Stroke is a devastating complication of sickle cell anemia (SCA), affecting up to 30% of children with the disease. Despite the relative frequency of stroke in SCA, few predictors of risk exist. Because stroke in SCA is likely a multifactorial disease, analysis of the combined effect of multiple genetic variants may prove more successful than evaluation of individual candidate genes. We genotyped 230 children with SCA for 104 polymorphisms among 65 candidate vascular genes to identify risk associations with stroke. Patients were phenotyped based on magnetic resonance imaging/angiography (MRI/MRA) findings into large-vessel (LV) versus small-vessel (SV) disease stroke subgroups. Specific polymorphisms in the IL4R 503, TNF (-308), and ADRB2 27 genes were independently associated with stroke susceptibility in the LV stroke subgroup, while variants in the VCAM1 (-1594) and LDLR NcoI genes were associated with SV stroke risk. The combination of TNF (-308)GG homozygosity and the IL4R 503P variant carrier status was associated with a particularly strong predisposition to LV stroke (odds ratio [OR] = 5.5; 95% confidence interval [CI] = 2.3-13.1). We show that several candidate genes may play a role in predisposition to specific stroke subtypes in children with SCA. If confirmed, these results provide a basis for population screening and targeted intervention to prevent stroke in SCA.
authors: Department of Hematology/Oncology, Children's Hospital and Research Center at Oakland, 747 52nd St, Oakland, CA 94609, USA. choppe@mail.cho.org
authors: Carolyn
authors: C
authors: Hoppe
authors: William
authors: W
authors: Klitz
authors: Suzanne
authors: S
authors: Cheng
authors: Ray
authors: R
authors: Apple
authors: Lori
authors: L
authors: Steiner
authors: Lara
authors: L
authors: Robles
authors: Tom
authors: T
authors: Girard
authors: Elliott
authors: E
authors: Vichinsky
authors: Lori
authors: L
authors: Styles
mesh_terms: D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000453:epidemiology* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D019948:Receptors, Interleukin-4 / Q000235:genetics; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D005819:Genetic Markers; D019948:Receptors, Interleukin-4; D014409:Tumor Necrosis Factor-alpha