Genetic Modifiers of Homozygous Beta Zero Thalassemia.

摘要: Introduction : Extensive studies over the last 50 years have derived two major modifiers of clinical expression beta-thalassemia: innate ability to produce fetal hemoglobin (Hb F) and co-inheritance alpha-thalassemia. Recently genetic variants at BCL11A locus HBS1L-MYB intergenic region, that can modulate Hb F levels been identified ( Thein et al 2007, Menzel 2007). Moreover, variant has shown moderate phenotype homozygous beta-thalassemia (Uda 2008). In this study we evaluated contribution these modulating markers alpha-thalassemia in ameliorating severity beta-thalassemia. Methods We studied patients with mild non-tranfusion dependent thalassemia intermedia 75 severe tranfusion major. All were homozygotes for beta 39 non-sense C → T mutation negative Xmn I -158 Gγ polymorphism. Alpha was detected by GAP-PCR technique (deletion defects) restriction enzyme digestion (nondeletion defects).Genotyping HbF performed using TaqMan® SNP genotyping assay (Applied Biosystems, Warrington, UK) according manufacturer’s protocol. Evaluation association, OR calculation test interaction fitting a logistic regression. Results found frequency co-inherited alpha- is significantly increased (p= 2.05 x 10 −5 , p= 8.1 −4 9.9 respectively) group intermedia. Interestingly, BCL 11A gene appears be greater than HBS 1L-MYB OR= 5.15 4.61 both are striking larger effect attributable (OR= 3.32). Furthermore, visualize combined effects all loci, considered score variable defined as number positive alleles (i.e. those associated amelioration phenotype) carried from each patient. When together three loci explain 79% variation, correlation between fitted observed values analyzed act an additive fashion, where copy minor allele contributes expression. Conclusions Molecular analysis particularly genome-wide association scans producing rapid advances defining complex diseases quantitative traits. The information reported relevant understanding genotype syndromes.