"Moreover, GWASs are necessarily broad in scope. They search the entire genome for associations rather than focusing on small candidate areas and they do not necessarily identify all relevant SNPs . Furthermore, all GWAS that evaluated SNPs for Hb decline while on treatment for CHC focused on end points at week 4 and could therefore only evaluate gene variations for short term Hb decline but not mid- to long-term Hb decline. "
[Show abstract][Hide abstract] ABSTRACT: Background
A decline in hemoglobin (Hb) concentration during antiviral therapy in chronic hepatitis C (CHC) is a serious side effect. It may compel to dose reduction or even termination of antiviral treatment. The activation of erythropoietin (EPO) synthesis as a physiological response to anemia and its relation to a genetic variation within the EPO gene has not been evaluated yet.
Data of 348 CHC patients were reviewed retrospectively. Samples were genotyped for EPO rs1617640 and inosine triphosphatase (ITPA) rs1127354. Serum EPO concentrations were determined before and during therapy. Primary endpoints were set as Hb decline >3 g/dl at weeks 4 and 12.
EPO rs1617640 G homozygotes showed a significantly lower rise of serum EPO level over time than T allele carriers (p < 0.001). The cumulative frequency of a significant Hb reduction added up to 40%. Multivariate analysis revealed that besides age, ribavirin starting dose and baseline Hb also EPO rs1617640 G homozygosity associates with Hb reduction at week 4 (p = 0.025) and 12 (p = 0.029), while ITPA C homozygotes are at risk for Hb decline particularly early during treatment. Furthermore, EPO rs1617640 G homozygotes were more frequently in need for blood transfusion, epoetin-α supplementation, or ribavirin dose reduction (p < 0.001).
Our data suggest that EPO rs1617640 genotype, the rise of serum EPO concentration as well as ITPA rs1127354 genotype are promising parameters to evaluate the Hb decline during antiviral therapy. A rational adjustment of therapy with epoetin-α supplementation might prevent serious adverse events or the need to terminate treatment.
[Show abstract][Hide abstract] ABSTRACT: In the conventional 3 db directional coupler, shown schematically in Figure 1a, equal output signals appear at ports 2 and 3 when port 1 is used as the input. No signal appears at port 4. The effective dielectric constant for the even mode (εre) must be approximately equal to the effective dielectric constant for the odd mode (εro) to assure equal propagation velocities which are essential for this type of coupler.
IEEE Transactions on Microwave Theory and Techniques 06/1967; 67(1):63- 65. DOI:10.1109/TMTT.1969.1127039 · 2.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Genetic testing for rare heart conditions might someday expand to more common cardiac ailments. Already there are signs testing is dramatically changing how some conditions are treated and doctors' definition of who a patient is. Stephen Strauss reports.
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