Beta S-gene-cluster haplotypes in sickle cell anemia: clinical implications.
Restriction endonuclease analysis was used to detect alpha-gene deletions and to determine the haplotypes in the DNA of the beta S-gene-cluster [Benin, Central African Republic (CAR), and Senegal] in 221 patients with sickle cell anemia (SS). The clinical expression of SS was modified by the beta S-gene-cluster polymorphisms and the alpha-gene status (alpha-thalassemia-2). The overall risk of soft tissue organ failure caused by the obliterative sickle vasculopathy (including stroke, renal failure, chronic lung disease with cor pulmonale, leg ulcers, and young adult death) was increased threefold in those with a CAR haplotype and was decreased in those with a Senegalese chromosome (p = 0.003). In the presence of a Senegalese haplotype, the patient's health is better, and with the CAR haplotype it is always worse. With the Benin, it is intermediate. Acute recurrent clinical events including hospitalized sickle cell crisis, bone infarction, and infection are decreased in frequency in those with a Senegalese haplotype. The risk of most acute events including acute chest syndrome is equivalent in those with Benin or CAR haplotypes. In the United States, alpha-thalassemia-2 is co-inherited randomly among the beta S-gene-cluster haplotypes. Acute events occurring during childhood are minimally effected by this co-inheritance. The risk of soft tissue organ failure is decreased. After the age of 20 years, painful episodes of the lumbar dorsal area are increased in patients who had alpha-thalassemia-2 in association with degenerative bone disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pediatrics, University of California School of Medicine, Los Angeles.
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Powars
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Chan
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Schroeder
D000755:Anemia, Sickle Cell / Q000150:complications / Q000208:ethnology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D001541:Benin / Q000208:ethnology; D002488:Central African Republic / Q000208:ethnology; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11; D005319:Fetal Hemoglobin / Q000032:analysis; D005914:Globins / Q000235:genetics*; D006239:Haplotypes; D006451:Hemoglobin, Sickle / Q000235:genetics*; D006801:Humans; D015993:Life Tables; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D012307:Risk Factors; D012675:Senegal / Q000208:ethnology; D012720:Severity of Illness Index; D015996:Survival Rate; D013789:Thalassemia / Q000150:complications / Q000235:genetics; D014481:United States / Q000453:epidemiology
D006451:Hemoglobin, Sickle; D005914:Globins; D005319:Fetal Hemoglobin