Browsing by Subject "Polymorphisms"

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    Biological assessment of aspirin efficacy on healthy individuals: heterogeneous response or aspirin failure?
    (2004-12-16) González-Conejero Hilla, Rocío; Rivera Pozo, José; Corral de la Calle, Javier; Acuña, Carmen; Vicente, Vincente; Guerrero López, José Antonio; Medicina Interna; Facultad de Medicina
    Background and Purpose— The widespread use of aspirin requires clarification of the aspirin resistance phenomenon. Most studies on this field are focused on patients which may affect the action of aspirin. Methods— We evaluated the biological efficacy of aspirin in healthy subjects. Results— Agonist–induced platelet aggregation was fully abrogated by 100 mg of aspirin in all individuals. By contrast, with the platelet function analyzer-100 device, 33.3% of the subjects displayed no response. This failure was overcome by 500 mg or by in vitro treatment of blood with 30 μmol/L acetylsalicylic acid. Intake of 100 mg of aspirin efficiently reduced by 75% the level of 11-dehydro thromboxane B2 (11-dTxB2) in all cases. However, variability on the pre-aspirin level (range 72.4 to 625.9 ng/mmol creatinine) led to substantial differences in the residual amount of the metabolite between subjects treated with aspirin (range 12.9 to 118.0 ng/mmol creatinine). Finally, there was no influence of platelet glycoprotein IIb/IIIa (Pro33Leu), platelet glycoprotein Ia/IIa, (C807T), and FXIII (Val34Leu) polymorphisms on the efficacy of aspirin. However, the cyclooxygenase (Cox)-1 50T allele associated with higher level of 11-dTxB2, both before and after aspirin. Moreover, the Cox-2 −765C variant displayed a slightly higher reduction in 11-dTxB2 level on treatment with aspirin. Conclusions— Our findings suggest that full resistance of healthy subjects to aspirin is rather unlikely. However, differences in aspirin absorption, or pharmacokinetic, or other unrecognized factors may lead to lack of effect of low dose of aspirin in some subjects when using tests like platelet function analyzer-100. Whether Cox polymorphisms are thrombotic risk factor for patients under aspirin will require further research.
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    Forensic avaluation and population genetic study of KIR2DS4 insertion/deletion polymorphisms in a Spanish population
    (Romanian Society of Legal Medicine, 2021-06) Bolarín, Jose Miguel; Pérez Cárceles, M. Dolores; Luna, Aurelio; Minguela, Alfredo; Muro, Manuel; Legez Pérez, Isabel; Ciencias Sociosanitarias
    Polymorphisms (Indels) of insertion/deletion are a class of diallelic genetic markers resulting from a single mutation event and reflect the insertion or deletion of genomic DNA bases. The aim of this study was to analyze the distribution of the allelic variants of KIR2DS4 in the Spanish Caucasian population and compared it with other populations described in the literature. Genotyping of allelic variants of KIR2DS4 was performed by PCR-SSO in 127 healthy Spanish Caucasian individuals and were subsequently compared with 26 different world populations. A frequency of KIR2DS4-full (36.2%) allelic variants was found in the Spanish population, similar to those found European populations, but different and higher frequency in South and Central America and the Caribbean, Saudi Arabia, Sub-Saharan African as well as Hong Kong and Korean populations. A frequency of 77.2% of KIR2DS4-delected variant was found in Spanish population, while lower percentages were found in Sub-Saharan Africa, China, Hong Kong and Korea. No differences in the distribution of KIR2DS4 variants were observed between AA/BX KIR haplotypes and genotypes. In conclusion, our results enrich the Caucasian genetic information of the KIR2DS4 allelic variants between the Spanish Caucasian and other populations that could be useful in clinical, forensic and anthropological studies.
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    Regulatory regions of SERPINC1 gene: identification of the first mutation associated with antithrombin deficiency
    (Thieme Gruppe, 2012) Morena-Barrio, Maria Eugenia de la; Antón, Ana Isabel; Martínez Martínez, Irene; Padilla, José; Miñano, Antonia; Navarro Fernández, José; Águila, Sonia; López, María Fernanda; Fontcuberta, Jordi; Vicente, Vicente; Corral, Javier; Medicina
    Antithrombin is the main endogenous anticoagulant. Impaired function or deficiency of this molecule significantly increases the risk of thrombosis. We studied the genetic variability of SERPINC1 , the gene encoding antithrombin, to identify mutations affecting regulatory regions with functional effect on its levels. We sequenced 15,375 bp of this gene, including the potential promoter region, in three groups of subjects: five healthy subjects with antithrombin levels in the lowest (75%) and highest (115%) ranges of our population, 14 patients with venous thrombosis and a moderate antithrombin deficiency as the single thrombophilic defect, and two families with type I antithrombin deficiency who had neither mutations affecting exons or flanking regions, nor gross gene deletions. Our study confirmed the low genetic variability of SERPINC1 , particularly in the coding region, and its minor influence in the heterogeneity of antithrombin levels. Interestingly, in one family, we identified a g.2143 C>G transversion, located 170 bp upstream from the translation initiation codon. This mutation affected one of the four regions located in the minimal promoter that have potential regulatory activity according to previous DNase footprinting protection assays. Genotype-phenotype analysis in the affected family and reporter analysis in different hepatic cell lines demonstrated that this mutation significantly impaired, although it did not abolish, the downstream transcription. Therefore, this is the first mutation affecting a regulatory region of the SERPINC1 gene associated with antithrombin deficiency. Our results strongly sustain the inclusion of the promoter region of SERPINC1 in the molecular analysis of patients with antithrombin deficiency.