Influence of the βs haplotype and α-thalassemia on stroke development in a Brazilian population with sickle cell anaemia.
Stroke is a catastrophic complication of sickle cell anaemia (SCA) and is one of the leading causes of death in both adults and children with SCA. Evidence suggests that some genetic polymorphisms could be related to stroke development, but their association remains controversial. Here, we performed genotyping of five published single nucleotide polymorphisms, the α-thalassemia genotype, the G6PD A (-) variant deficiency, and the β(S) haplotype in a large series of SCA patients with well-defined stroke phenotypes. Of 261 unrelated SCA patients included in the study, 67 (9.5 %) presented a documented, primary stroke event. Markers of haemolysis (red blood cell (RBC) counts, p = 0.023; reticulocyte counts, p = 0.003; haemoglobin (Hb) levels, p < 0.001; indirect bilirubin levels, p = 0.006; lactate dehydrogenase (LDH) levels, p = 0.001) were associated with stroke susceptibility. Genetically, only the β(S) haplotype (odds ratio (OR) 2.9, 95 % confidence interval (CI) 1.56 to 4.31; p = 0.003) and the α(3.7kb)-thalassemia genotype (OR 0.31, 95 % CI 0.11 to 0. 83; p = 0.02) were associated with increased and decreased stroke risk, respectively. In multivariate analysis, the β(S) haplotype was independently associated with stroke development (OR 2.26, 95 % CI 1.16 to 4.4; p = 0.016). Our findings suggest that only the β(S) haplotypes and the α(3.7kb)-thalassemia genotype modulate the prevalence of stroke in our SCA population. Genetic heterogeneity among different populations may account for the irreproducibility amongst different studies.
Department of Genetics, Centre of Biological Sciences, Federal University of Pernambuco, Av. Prof. Moraes Rego, 1235, Recife, PE, 50670-901, Brazil.
Igor F
IF
Domingos
Diego A
DA
Falcão
Betania L
BL
Hatzlhofer
Anderson F
AF
Cunha
Magnun N
MN
Santos
Dulcinéia M
DM
Albuquerque
Kleber Y
KY
Fertrin
Fernando F
FF
Costa
Renata C
RC
Azevedo
Cíntia G
CG
Machado
Aderson S
AS
Araújo
Antonio R
AR
Lucena-Araujo
Marcos A
MA
Bezerra
D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D001938:Brazil / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011159:Population Surveillance / Q000379:methods; D020521:Stroke / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult; D017085:alpha-Thalassemia / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D017086:beta-Thalassemia / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*