RGD Reference Report - Gene interactions and stroke risk in children with sickle cell anemia. - Rat Genome Database

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Gene interactions and stroke risk in children with sickle cell anemia.

Authors: Hoppe, C  Klitz, W  Cheng, S  Apple, R  Steiner, L  Robles, L  Girard, T  Vichinsky, E  Styles, L   
Citation: Hoppe C, etal., Blood. 2004 Mar 15;103(6):2391-6. Epub 2003 Nov 13.
RGD ID: 11529997
Pubmed: PMID:14615367   (View Abstract at PubMed)
DOI: DOI:10.1182/blood-2003-09-3015   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Stroke susceptibilityIAGP 11529997associated with Anemia more ...RGD 
Stroke susceptibilityISOIL4R (Homo sapiens)11529997; 11529997associated with Anemia more ...RGD 
Stroke susceptibilityIAGP 11529997associated with Anemia more ...RGD 
Stroke susceptibilityISOTNF (Homo sapiens)11529997; 11529997associated with Anemia more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il4r  (interleukin 4 receptor)
Tnf  (tumor necrosis factor)

Genes (Mus musculus)
Il4ra  (interleukin 4 receptor, alpha)
Tnf  (tumor necrosis factor)

Genes (Homo sapiens)
IL4R  (interleukin 4 receptor)
TNF  (tumor necrosis factor)


Additional Information