Duffy blood group system genotyping in an urban Tunisian population.

BACKGROUND: The Duffy blood group system, besides its relevance in transfusion medicine, is of major interest for population genetics. In fact, the Duffy molecule is the only red cell receptor for Plasmodium vivax, thus the fixation of FY*silent allele in western south-Saharan Africa resulted in the absence of this type of malaria in that area (for a review see Kwiatowski, Am J Hum Genet 77:171-192, 2005). For the Duffy functional role see, for example, Daniels (Vox Sanguinis 93:331-340, 2007). METHODS: Duffy blood group distribution in 115 unrelated Tunisians was determined using the polymerase chain reaction with sequence specific primer (PCR-SSP) method detecting the five allelic versions of the FY gene. The red cell antigenic FY phenotype, for each donor, was deduced through DNA analysis. The blood samples of the positive FY*X alleles were investigated by serological methods, mainly the fixation-elution technique. RESULTS: The following allele frequencies were found (after having excluded FY*X, which had frequency of 0.0174): FY*1 = 0.291 (expressed 0.260; silent 0.031); FY*2 = 0.709 (expressed 0.427; silent 0.282). The most surprising result in this work is the detection of the FY*1 silent allele, usually quite rare, in four samples (1.74%). For FY*2 silent, the predominant allele in Africans, genotyping results showed a prevalence of 29.57%. The FY locus was in Hardy-Weinberg equilibrium in the present sample. CONCLUSION: When compared with European and African data, Tunisian samples demonstrated the presence of the common signs of these two ancestries (FY*2 and FY*X for the first population; and FY*2 silent for the last one). These data confirm the mixed roots of this urban Tunisian population already suggested by numerous studies on other haematological markers.

Prevalence of C282Y and H63D mutations in the haemochromatosis (HFE) gene in Tunisian population.

The studies of the HFE mutations: H63D and C282Y in North African populations have revealed the extreme rarity or even the absence of the C282Y mutation. We have examined 1140 chromosomes (570 Tunisian people) for the presence of the two HFE mutations by PCR-RFLP analysis. We have found that the allele frequencies are, respectively, 15.17% (+/-2.1%) for the H63D and 0.09% (+/-0.17%) for the C282Y. These results are consistent with the worldwide spread of the H63D mutation and the north European restriction of the C282Y. This study will be completed by determining whether homozygote trait for H63D and associated risk factors (beta thalassémia) can lead to iron overload in Tunisia.

Plasma coenzyme Q10 concentrations in breast cancer: prognosis and therapeutic consequences.

BACKGROUND: Coenzyme Q10 or ubiquinone is a redox component of the respiratory chain, which may be involved in the pathogenesis of cancer. METHODS: In order to better understand the role of this vitamin in the pathogenesis of breast cancer, a clinical trial including 200 women hospitalized for the biopsy and/or the ablation of a breast tumor was conducted. Ubiquinone plasma concentrations were determined simultaneously with vitamin E plasma concentrations (as antioxidant reference) by HPLC. RESULTS: A coenzyme Q10 deficiency was noted both in carcinomas (80 patients) and non-malignant lesions (120 patients), while vitamin E concentrations were within the normal range. A correlation was shown between the intensity of the deficiency and the bad prognosis of the breast disease based on high TNM and SBR values or the lack of estrogen receptors. However, neither cathepsin D level nor adenopathy invasion was related to ubiquinone levels. CONCLUSIONS: Since prooxidants may promote tumorigenesis, ubiquinone supplementation in breast cancer could be relevant.

The genetic variant A of human alpha 1-acid glycoprotein limits the blood to brain transfer of drugs it binds.

The objective of this work was to check the effects of alpha-1 acid glycoprotein (AAG) and of its components, A and F1/S genetic variants, on the brain transfer of drugs they bind in plasma. The relevant extractions of six basic drugs, highly bound to AAG, were measured. We chose three drugs selectively bound to the A variant, disopyramide, imipramine and methadone, one drug mainly bound to the mixture F1/S, mifepristone, and two drugs which were simultaneously bound to the variant A and the mixture F1/S, propranolol and chlorpromazine. Their brain extraction were investigated in rats using the carotid injection technique and the capillary depletion method. Injected drugs were dissolved either in buffer, either in native AAG containing the three variants (A, F1 and S), either in variant A or in variant F1/S solutions. Brain extractions of disopyramide, imipramine and methadone were significantly reduced by native AAG and by variant A. Drug's plasma retention was related to their preferential and almost exclusive binding to A variant, both of them exhibiting the same decrease in brain transfer as compared to a buffered solution. At the opposite, there were no significative differences between the extraction either in buffer, either in AAG or in F1/S solutions, of drugs both bound to A variant and F1/S mixture (chlorpromazine and propranolol) or to the F1/S mixture (mifepristone). In serum, the retentional effect of the A variant on the extraction of disopyramide and imipramine was counteracted by the presence of albumin and lipoproteins, which simultaneously bind these two drugs at a high extent and act as permissive binders. We conclude that AAG binding decreases brain drug transfer when the A variant is mainly and almost exclusively involved in the binding. On the contrary, the entire fraction of the tested drugs when bound exclusively or partly to the mixture F1/S is available for transfer into the brain.