Genetic Etiologies for Phenotypic Diversity in Sickle Cell Anemia

Steinberg, Martin H.

doi:10.1100/tsw.2009.10

Cited by 167 publications

(139 citation statements)

References 117 publications

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“…The Cameroon haplotype has previously been associated with poor clinical outcome and increased stoke episodes in SCD (Adorno et al, 2008;Steinberg et al, 1998), whereas the Benin haplotype is thought to confer a relatively favorable clinical outcome (Steinberg, 2009). In a previous report, we anticipated that the relatively high prevalence of stroke in SCD patients in Cameroon could be attributed to the high proportion of Cameroonian haplotype (Njamnshi et al, 2006).…”

Section: Fig 2 Global Distribution Of Haplotypes Among Various Worlmentioning

confidence: 97%

“…Four haplotypes are associated with HbS in Africa (Benin, Bantu/Central African Republic (CAR), Senegal, and Cameroon) and the fifth is thought to have arisen in India and/or the Arabian Peninsula (Arab/Hindu) (Elion et al, 1992;Pagnier et al, 1984). It has been suggested that these haplotypes also have an effect on the severity of the disease (Asultan et al, 2012;Steinberg, 2009) and possibly the clinical response to hydroxyurea (Friedrisch et al, 2008)-currently the only available treatment for SCD. Furthermore, these haplotypes have a well-defined geographic distribution in Africa, making it possible to establish the origin of African-descendant populations in America (Pagnier et al, 1984;Serjeant, 1989), but also the origin of SCD among Europeans from Mediterranean regions.…”

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confidence: 99%

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Beta-Globin Gene Haplotypes Among Cameroonians and Review of the Global Distribution: Is There a Case for a Single Sickle Mutation Origin in Africa?

Bitoungui

Pule

Hanchard

et al. 2015

OMICS: A Journal of Integrative Biology

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Studies of hemoglobin S haplotypes in African subpopulations have potential implications for patient care and our understanding of genetic factors that have shaped the prevalence of sickle cell disease (SCD). We evaluated HBB gene cluster haplotypes in SCD patients from Cameroon, and reviewed the literature for a global distribution. We reviewed medical records to obtain pertinent socio-demographic and clinical features for 610 Cameroonian SCD patients, including hemoglobin electrophoresis and full blood counts. RFLP-PCR was used to determine the HBB gene haplotype on 1082 chromosomes. A systematic review of the current literature was undertaken to catalogue HBB haplotype frequencies in SCD populations around the world. Benin (74%; n = 799) and Cameroon (19%; n = 207) were the most prevalent haplotypes observed among Cameroonian patients. There was no significant association between HBB haplotypes and clinical life events, anthropometric measures, hematological parameters, or fetal hemoglobin (HbF) levels. The literature review of the global haplotype distributions was consistent with known historical migrations of the people of Africa. Previously reported data from Sudan showed a distinctly unusual pattern; all four classical haplotypes were reported, with an exceptionally high proportion of the Senegal, Cameroon, and atypical haplotypes. We did not observe any significant associations between HBB haplotype and SCD disease course in this cohort. Taken together, the data from Cameroon and from the wider literature suggest that a careful reassessment of African HBB haplotypes may shed further light on the evolutionary dynamics of the sickle allele, which could suggest a single origin of the sickle mutation.

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Section: Fig 2 Global Distribution Of Haplotypes Among Various Worlmentioning

confidence: 97%

mentioning

confidence: 99%

Beta-Globin Gene Haplotypes Among Cameroonians and Review of the Global Distribution: Is There a Case for a Single Sickle Mutation Origin in Africa?

Bitoungui

Pule

Hanchard

et al. 2015

OMICS: A Journal of Integrative Biology

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“…Within the hemoglobin S genotype, haplotypes of the S gene appear to be related to specific phenotypes of the disease, including pain phenotypes. 50 …”

Section: Genetic Predictorsmentioning

confidence: 99%

Sickle-Cell Pain: Advances in Epidemiology and Etiology

Smith

Scherer

2010

Hematology

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New epidemiological findings recast pain in sickle-cell disease (SCD) as being more often a chronic manifestation than was previously thought, although acute pain is still the hallmark of the disease. SCD pain intensity, the number of painful locations, and the frequency of hospitalizations due to SCD pain may worsen with age. In adults and even in children, the quantity and severity of SCD pain may be vastly underestimated, because most of the "iceberg" of SCD pain is "submerged" at home, and only the tip of the iceberg is seen by health care providers when acute SCD care is rendered in emergency rooms and hospitals. Implications of this "iceberg phenomenon" are significant for clinicians, researchers, employers, policy makers, and the public. Nevertheless, both emergency room and hospital utilization for SCD pain remain prevalent. Often, utilization recurs early, perhaps emblematic of poor acute pain management. New data show the protean impacts of SCD pain on health-related quality of life, sleep, and psychological and social health. The relationship of the severity of SCD pain to the severity of underlying sickle vasculopathy is unclear, but epidemiologic evidence and patient descriptors suggest a temporal evolution of pain mechanisms. At first, increasingly worse nociceptive pain from vaso-occlusion and local lesions may evolve over the first two decades of life. Then, in the third and following decades, central neuropathic pain may also evolve due to past and continuing nociceptive stimuli. New findings confirm environmental contributors to SCD pain, including seasonal (colder) temperatures, barometric pressure, and wind speed.

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“…Elevated Hb F levels are known to improve the clinical manifestations of the two largest known hemoglobin changes: sickle cell disease and β-thalassemia. In sickle cell disease, the Hb F concentration and distribution among the red blood cells are the main genetic modulators of the disease, whereas high levels of this hemoglobin dilute the amount of Hb S, inhibiting or delaying the polymerization process, which results in reduced disease severity (Steinberg, 2009). In homozygous β-thalassemia, increased production of γ chains helps in re-γ chains helps in reducing the imbalance of α and non-α chains and increasing total hemoglobin levels (Galanello and Cao, 1998;Thein, 2005).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of HPFH and δβ-thalassemia mutations in a Brazilian group with high Hb F levels

Carrocini¹,

Ondei²,

Zamaro³

et al. 2011

Genet. Mol. Res.

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ABSTRACT. Fetal hemoglobin (Hb F) is characteristic of the fetal development period. However, in some genetic conditions, such as hereditary persistence of fetal hemoglobin (HPFH) and deltabeta thalassemia (δβ-thalassemia), Hb F continues to be produced in adulthood. We evaluated the frequency of two mutations of HPFH, HPFH-1 and HPFH-2 African, and two mutations in δβ-thalassemia, Sicilian and Spanish, in a Brazilian population. Peripheral blood samples were collected from adults from hospitals and blood centers in southeast and northeast Brazil. These individuals were healthy and without complaints of anemia, but had increased Hb F. Samples were submitted to electrophoretic and chromatographic analyses to quantify Hb F values and, subsequently, to molecular analyses to verify the mutations. In the molecular analysis, 16 of the 60 samples showed a heterozygous profile for the HPFH mutations, two for HPFH-1 and 14 for HPFH-2. In the same sample set, three were heterozygous for Spanish δβ-thalassemia and none were heterozygous for Sicilian δβ-thalassemia. The Hb F values in the HPFH-2 heterozygotes differed from those previously reported for this mutation. In this group, the HPFH mutations were more frequent than the δβ-thalassemia mutations. The finding of these mutations in this Brazilian population reflects the mixing process that occurred during its formation.

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Genetic Etiologies for Phenotypic Diversity in Sickle Cell Anemia

Cited by 167 publications

References 117 publications

Beta-Globin Gene Haplotypes Among Cameroonians and Review of the Global Distribution: Is There a Case for a Single Sickle Mutation Origin in Africa?

Beta-Globin Gene Haplotypes Among Cameroonians and Review of the Global Distribution: Is There a Case for a Single Sickle Mutation Origin in Africa?

Sickle-Cell Pain: Advances in Epidemiology and Etiology

Evaluation of HPFH and δβ-thalassemia mutations in a Brazilian group with high Hb F levels

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