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Mutations and polymorphisms in hemoglobin genes and the risk of pulmonary hypertension and death in sickle cell disease
- Source :
- American Journal of Hematology. 83:6-14
- Publication Year :
- 2008
- Publisher :
- Wiley, 2008.
-
Abstract
- Pulmonary hypertension is a common complication of sickle cell disease (SCD) and a risk factor for early death. Hemolysis may participate in its pathogenesis by limiting nitric oxide (NO) bioavailability and producing vasculopathy. We hypothesized that hemoglobin mutations that diminish hemolysis in SCD would influence pulmonary hypertension susceptibility. Surprisingly, coincident α-thalassemia (OR = 0.95, 95% CI = 0.46 – 1.94, P = NS) was not associated with pulmonary hypertension susceptibility in homozygous SCD. However, pulmonary hypertension cases were less likely to have hemoglobin SC (Odds Ratio [OR] = 0.18, 95% confidence interval [CI] = 0.06 to 0.51, P = 0.0005) or Sβ+ thalassemia (OR = 0.25, 95% CI = 0.06 to 1.16, P = 0.10). These compound heterozygotes may be protected from pulmonary hypertension because of reduced levels of intravascular hemolysis, but develop this complication at a lower rate possibly due to the presence of non-hemolytic risk factors such as renal dysfunction, iron overload and advancing age. Despite this protective association, patients with SC who did develop pulmonary hypertension remained at significant risk for death during 49 months of follow-up (Hazard Ratio=8.20, P=0.0057).
- Subjects :
- Adult
Genetic Markers
Male
Hemolytic anemia
medicine.medical_specialty
Pathology
Hypertension, Pulmonary
Thalassemia
Anemia, Sickle Cell
Gastroenterology
Article
Cohort Studies
Hemoglobins
Age Distribution
alpha-Thalassemia
Risk Factors
Internal medicine
medicine
Humans
False Positive Reactions
Genetic Predisposition to Disease
Risk factor
Alleles
Chromatography, High Pressure Liquid
Polymorphism, Genetic
business.industry
Chromosomes, Human, Pair 11
Respiratory disease
Hematology
Odds ratio
medicine.disease
Pulmonary hypertension
Sickle cell anemia
Survival Rate
Phenotype
Hemoglobinopathy
Haplotypes
Mutation
Female
business
Subjects
Details
- ISSN :
- 10968652 and 03618609
- Volume :
- 83
- Database :
- OpenAIRE
- Journal :
- American Journal of Hematology
- Accession number :
- edsair.doi.dedup.....aaf6f8b4eb28960a34a074b59e37b88c