Genetic Testing in Clinical Settings

Abstract

Genetic testing is used for screening, diagnosis, and prognosis of diseases consistent with a genetic cause and to guide drug therapy to improve drug efficacy and avoid adverse effects (pharmacogenomics). This In Practice review aims to inform about DNA-related genetic test availability, interpretation, and recommended clinical actions based on results using evidence from clinical guidelines, when available. We discuss challenges that limit the widespread use of genetic information in the clinical care setting, including a small number of actionable genetic variants with strong evidence of clinical validity and utility, and the need for improving the health literacy of health care providers and the public, including for direct-to-consumer tests. Ethical, legal, and social issues and incidental findings also need to be addressed. Because our understanding of genetic factors associated with disease and drug response is rapidly increasing and new genetic tests are being developed that could be adopted by clinicians in the short term, we also provide extensive resources for information and education on genetic testing.

The effect of APOL1 risk variants on emergent outcomes in kidney disorders: A meta-analysis of individual participant data

“…Furthermore, metabolic syndrome was seen in 15% (3/20) of patients in this research. Our study revealed an increased risk of 1.13 and odds of 1.5 for ESKD in high-risk allele group in this research but the study by Franceschini et al said individuals carrying two APOL1 risk genotype (high risk; 13% Africans Americans and 2% of U.S. Hispanics/Latinos of Caribbean background) have an increased risk for ESKD (odds ratio of ∼7) and for FSGS odds ratio of 10 to 29 including HIV nephropathy [29]. The present study showed a lower mean age of ESKD and hemodialysis onset in high vs low-risk allele group.…”

Analytical validity of a genotyping assay for use with personalized antihypertensive and chronic kidney disease therapy

“…These genes include APOL1 , relevant to individuals with African ancestry, as well as other genes identified from African-American, Asian and Caucasian populations, with or without diabetes mellitus. Their clinical validity has been reviewed elsewhere [23].…”

<p>Physicians’ Attitudes and Ethical Obligations to Pharmacogenetic Testing</p>

“…Pharmacogenetic (PGt) testing as a relatively new tool for the personalized treatment and prevention of chronic diseases, is a significant medical advancement. 1 While PGt studies investigate individuals' responses to medications based on single-gene mutations, pharmacogenomics (PGx) approaches imply the study of many genes or whole sets of genes. 2 Although PGt has potential to improve drug safety and efficacy, its acceptance in medical practice depends heavily on the ethical issues that need to be addressed to ensure the appropriate use of PGt testing.…”

“…2 Although PGt has potential to improve drug safety and efficacy, its acceptance in medical practice depends heavily on the ethical issues that need to be addressed to ensure the appropriate use of PGt testing. 1 Some ethical challenges arise from the application of ethical principles that support patient autonomy and confidentiality on one hand, 3 and what genetic information can be revealed on the other hand. 4 After the successful completion of Human Genomic Project, the availability of DNA sequences has rapidly advanced the diagnosis of genetic diseases by identifying genetic markers that link inherited genetic diseases with the responsible genes.…”

“…5 Another field of genetic testing application that evaluates the safety and efficacy of medication is drug-gene testing or PGt testing that can be used to assess how genetic variations influence individuals' response to medications. 1 Genetic variations in CYPs P450-mediated drug metabolism can significantly affect the rate of drug metabolism among different individuals. For instance, polymorphism in the CYP2C9 gene is responsible for about a 30% to 90% reduction in the enzymatic activity and subsequently the inter-individual unpredictability of warfarin clearance from the body.…”