Warfarin therapy is complicated by a narrow therapeutic index and substantial interpatient variability in dose response. The cytochrome P450 (CYP)2C9 and vitamin K epoxide reductase complex 1 (VKORC1) genes have recently been determined to be associated with warfarin dose requirements, with reduced doses of this drug being required in patients with the variant CYP2C9*2, CYP2C9*3, or VKORC1 -1639A allele. The combination of genotype and clinical factors explains approximately 50 to 60% of the variance in warfarin dose requirements in Caucasians and Asians, but only 25 to 40% among African Americans. Racial differences in the association between genotype and a patient's response to warfarin treatment may be caused by racial differences in the frequencies of the variant CYP2C9*2, CYP2C9*3, and VKORC1 -1639A alleles or by the influence of non-genetic factors. Genotype also influences the time required to attain therapeutic anticoagulation and the risk for over-anticoagulation and hemorrhage. Although the incorporation of genotype information improves the accuracy of dose prediction, an improvement in anticoagulation control or a reduction in hemorrhagic complications has not been demonstrated. Therefore, the routine use of CYP2C9 and VKORC1 genotyping is not supported by currently available evidence. The results of ongoing or future multicenter clinical trials are expected to clarify the role of pharmacogenomics in the management of warfarin therapy.
[Show abstract][Hide abstract] ABSTRACT: Responses to toxins and drugs, even to standard medical drug treatment regimens, can vary significantly between individuals. Similar dosages can have divergent results due to polymorphisms in the genes that code for the enzymes responsible for the metabolism of drugs. The focus of this report is to describe our exploration of the personalized medicine approach for patient care at Sydney West Area Health Service. We would like to demonstrate the importance of this approach as it is the subject of debate in the medical and scientific community. The critical points in this debate are the cost of testing, laboratory space required and clinical application. We have shown that a simple approach and instruments like the Agilent Bioanalyzer could be cost effective for laboratory operation. The Agilent Bioanalyzer (Agilent Technologies, CA, USA) can be used for proteins, DNA and cell studies. Hence, reduced cost of instruments, laboratory space requirements, maintenance and operational costs are great advantages of this technology, especially for development and research laboratories.
[Show abstract][Hide abstract] ABSTRACT: Clinical journals are reporting genetic associations with systemic lupus erythematosus (SLE) with increasing frequency. Interpreting these studies is difficult for clinicians without rigorous training in epidemiology, statistics, and genetics. In this review, we discuss basic issues important to understanding and contextualizing new genetic association studies. We, therefore, highlight literature related to methodology as well as recent genetic discoveries in SLE.
Functional single nucleotide polymorphisms (SNPs) and/or haplotypes have now been identified for ITGAM, PTPN22, and IRF5, and several additional loci have been highlighted in recent genome-wide association studies in SLE. Recent work also indicates that several regions within the extended major histocompatibility complex contribute independently to SLE risk. Evidence of additive statistical interaction has been found between IRF5 and TYK2, IRF5, and STAT4, and between NAT2 and exposure to tobacco smoke.
Many new genes have been associated with SLE susceptibility, revealing insight into SLE pathophysiology. Current research is focusing on further refining the initial genetic association results and extending this work to non-European populations. Research is also expanding beyond SNP associations to investigate the contribution of copy number variants (CNVs) and DNA methylation to SLE risk.
Current opinion in rheumatology 03/2010; 22(2):119-25. DOI:10.1097/BOR.0b013e3283361943 · 4.89 Impact Factor
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