-
Ryad Tamouza,
Marc Busson,
Catherine Fortier,
Ibrahima Diagne,
Dapa Diallo,
Ivan Sloma,
Hector Contouris,
Rajagopal Krishnamoorthy, Dominique Labie,
Robert Girot,
Dominique Charron
[show abstract]
[hide abstract]
ABSTRACT: Severe bacterial infections are the major causes of morbidity and mortality in sickle cell anemia (SCA) but are poorly explained. The distribution of a bi-allelic polymorphism (Arg107Gly) of human leukocyte antigen-E (HLA-E) locus was investigated in 144 SCA patients, most of whom originated from from sub-Saharan Africa. Among them, 73 presented with at least one severe bacterial infection, whereas 71 did not. The HLA-E*0101/E*0101 genotype was more frequent among the group with infections than their counterparts (47% vs 21%; p corrected = 0.003). This genetic association is of relevance, given the emerging evidence for the involvement of HLA-E molecules in host response to pathogens.
Human Immunology 11/2007; 68(10):849-53. · 2.84 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We report on two families in which the beta(0)-thalassemia mutation IVS2+1G-->A occurs either in the homozygous or compound heterozygous condition with other beta-thalassemia determinants. In the first family the proband, homozygous for the IVS2+1 determinant, is asymptomatic and was detected by chance during a screening program for beta-thalassemia. In the second family, the proband is a 43-year old female with a very mild thalassemia intermedia due to compound heterozygosity for the IVS2+1G>A and IVS1+110G>A mutations. Her father was diagnosed as having a thalassemic disorder only during the family studies carried out because of the proband's condition. He is a compound heterozygote for the Sicilian type deltabeta(0)-thalassemia and the IVS2+1 mutation and has a normal level of hemoglobin.
In both families, the heterozygous carriers of the IVS2+1G>A have unusually elevated levels of fetal hemoglobin (HbF), and the homozygotes showed 98% HbF, reflecting an increased production of well hemoglobinized F-cells not associated with a significant erythroid expansion.
The high HbF levels co-segregate with the beta-thalassemia mutation; the size and structure of both pedigrees do not allow the contribution of unlinked genes to the elevated production of HbF to be assessed.
We propose that the unusual phenotypes resulting from homozygosity and compound heterozygosity for IVS2+1 are, against the background of a polygenic quantitative control of HbF expression, principally due to elements, such as repetitive sequences or single nucleotide polymorphisms, within or closely linked to the beta-gene cluster. These are potentially implicated in chromatin environment modifications, and could, therefore, be responsible for sustained HbF synthesis during development.
Haematologica 10/2003; 88(10):1099-105. · 6.42 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Despite systematic antibiotic therapy, severe infections (septicemia, meningitis, or osteomyelitis) are a major cause of mortality and morbidity in children with sickle cell disease (SCD). In this study, we explored the possibility that polymorphism at the human leukocyte antigen (HLA) locus might constitute an immunogenetic modifying factor to the intrinsic susceptibility to infection in patients with SCD. A cohort of 80 SCD patients living in Paris, 43 with at least one major infectious complication and 37 without infections, were typed for HLA class II loci by polymerase chain reaction-sequence-specific primers (PCR-SSP). We found that significantly more patients without infections carry the HLA class II DRB1*15 specificity than did patients with infections (21.6% in the first group, versus 4.7% in the second group; chi(2) = 10.47, p(c) = 0.01), supporting a protective effect of this allele. Conversely, significantly more patients were found to carry the DQB1*03 specificity within the group of severe infections, supporting a negative effect (34.9% versus 12.2%, chi(2) = 9.41, p(c) = 0.01). These findings suggest a direct involvement of HLA polymorphism in the development of major infections in SCD. Together with previous data on polymorphism of the Fc receptor and of the mannose-binding lectin, they provide evidence for a polygenic immunomodulation of the constitutively increased infectious risk in SCD.
Human Immunology 04/2002; 63(3):194-9. · 2.84 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the allelic frequency and genetic diversity of α-thalassemia defects in Sicily, both epidemiological and patient-oriented
studies were carried out. For the epidemiological study, phenotypic data were collected on more than 1000 Sicilian individuals.
Among them, 427 were explored at the molecular level for nine α-thalassemic variants known to be common in the Mediterranean
region. Our data reveal an allele frequency of 4.1% for α+-thalassemia matching that of β-thalassemia in this region. The presence of α°-thalassemia (––MEDI and ––CAL) was observed only in the group of referred patients. Newly acquired nucleotide sequence data on the deletional breakpoint
of ––CAL allowed us to design a simple PCR-based procedure for exploring this allele. The data also provide additional information
concerning the genetic mechanisms involved in such large deletions.
Human Genetics 01/1997; 99(3):381-386. · 5.07 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Sequence polymorphisms within the 5HS2 segment of human locus control region is described among sickle cell anemia patients. Distinct polymorphic patterns of a simple sequence repeat are observed in strong linkage disequilibrium with each of the five major S haplotypes. Potential functional relevance of this polymorphic region in globin gene expression is discussed.
Human Genetics 05/1993; 91(5):464-468. · 5.07 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The frequency of +-thalassmia has been determined in African populations carrying s-chromosomes of different origins. All these + thalassemias result from a right-ward deletion. Restriction mapping of the -37/haplotype with the enzyme ApI only showed the presence of a type I crossover. RsaI polymorphism at the 5 end of Z2 is largely represented in the normal population (gene frequency 23%) but, in our series, never associated with the -37/haplotype.
Human Genetics 01/1988; 78(2):193-195. · 5.07 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Phenotypic expression of sickle cell disease (SCD) is highly variable. We investigated red blood cells (RBCs) and reticulocytes using a laser light scattering method (ADVIA120, Bayer Diagnostics, Tarrytown, NY) in a series of patients with either sickle cell anemia (SS) or compound SC heterozygosity (SC), both groups with or without alpha thalassemia. Results were compared with those of a series of patients without hematological disease. Known data were consistently confirmed, namely heterogeneity in cell volume and hemoglobin (Hb) concentration, as well as the premature exit of "stress" reticulocytes from the bone marrow, mostly in SS patients. Specific changes were observed during maturation, including decreases in macrocytic and hypodense cells. Simultaneous viewing of the indices of the different RBC populations provided information on erythropoietic maturation by a rapid, reproducible, and cost-effective method.
Blood Cells Molecules and Diseases 33(1):15-24. · 2.35 Impact Factor
-
Medecine sciences: M/S 22(6-7):571-2. · 0.64 Impact Factor
-
Medecine sciences: M/S 20(8-9):743-6. · 0.64 Impact Factor
