Genetic Dissection and Prognostic Modeling of Overt Stroke in Sickle Cell Anemia

Overview

Journal Nat Genet

Specialty Genetics

Date 2005 Mar 22

PMID 15778708

Citations 112

Authors

Paola Sebastiani

Marco F Ramoni

Vikki Nolan

Clinton T Baldwin

Martin H Steinberg

Affiliations

Soon will be listed here.

Abstract

Sickle cell anemia (SCA) is a paradigmatic single gene disorder caused by homozygosity with respect to a unique mutation at the beta-globin locus. SCA is phenotypically complex, with different clinical courses ranging from early childhood mortality to a virtually unrecognized condition. Overt stroke is a severe complication affecting 6-8% of individuals with SCA. Modifier genes might interact to determine the susceptibility to stroke, but such genes have not yet been identified. Using Bayesian networks, we analyzed 108 SNPs in 39 candidate genes in 1,398 individuals with SCA. We found that 31 SNPs in 12 genes interact with fetal hemoglobin to modulate the risk of stroke. This network of interactions includes three genes in the TGF-beta pathway and SELP, which is associated with stroke in the general population. We validated this model in a different population by predicting the occurrence of stroke in 114 individuals with 98.2% accuracy.

Citing Articles

Genetic Modifiers of Stroke in Patients with Sickle Cell Disease-A Scoping Review.

Oni M, Brito M, Rotman C, Archer N Int J Mol Sci. 2024; 25(12).

PMID: 38928024 PMC: 11203960. DOI: 10.3390/ijms25126317.

Impact of Genetic Variations on Thromboembolic Risk in Saudis with Sickle Cell Disease.

Alshabeeb M, Alwadaani D, Al Qahtani F, Abohelaika S, Alzahrani M, Al Zayed A Genes (Basel). 2023; 14(10).

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Genetic Variation and Sickle Cell Disease Severity: A Systematic Review and Meta-Analysis.

Kirkham J, Estepp J, Weiss M, Rashkin S JAMA Netw Open. 2023; 6(10):e2337484.

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The future of sickle cell disease therapeutics rests in genomics.

Wonkam A Dis Model Mech. 2023; 16(2).

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Genome-wide association study of early ischaemic stroke risk in Brazilian individuals with sickle cell disease implicates ADAMTS2 and CDK18 and uncovers novel loci.

Earley E, Kelly S, Fang F, Alencar C, Werneck Rodrigues D, Soares Cruz D Br J Haematol. 2023; 201(2):343-352.

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