Discover the most talked about and latest scientific content & concepts.

Journal: Pharmacogenomics


We investigate the role of ethnicity and admixture in drug response across a broad group of chemotherapeutic drugs. Also, we generate hypotheses on the genetic variants driving differential drug response through multivariate genome-wide association studies.

Concepts: Cancer, Breast cancer, Oncology, Chemotherapy, Radiation therapy, Leukemia, Lymphoma, Targeted therapy


Background: Patients with mutations or deletions of the SHOX gene present variable growth impairment, with or without mesomelic skeletal dysplasia. If untreated, short patients with SHOX haplodeficiency (SHOXD) remain short into adulthood. Although recombinant human growth hormone (rhGH) treatment improves short-term linear growth, there are episodic data on the final height of treated SHOXD subjects. Patients & methods: After a thorough search of the published literature for pertinent studies, we undertook a meta-analysis evaluation of the efficacy and safety of rhGH treatment in SHOXD patients. Results: In SHOXD patients, administration of rhGH progressively improved the height deficit from baseline to 24 months, although the major catch-up growth was detected after 12 months. The rhGH-induced growth appeared constant until final height. Conclusion: Our meta-analysis suggested rhGH therapy improves height outcome of SHOXD patients, though future studies using carefully titrated rhGH protocols are needed. Original submitted 29 October 2012; Revision submitted 22 February 2013.

Concepts: Immune system, Recombinant DNA, Growth hormone, Turner syndrome, Endocrine gland, Growth hormone deficiency, Idiopathic short stature


This study aimed to compare the clinical and economic outcomes of pharmacogenetic-guided (PG-guided) and platelet reactivity testing-guided antiplatelet therapy for patients with acute coronary syndrome undergoing percutaneous coronary intervention.

Concepts: Clopidogrel, Cost-effectiveness analysis


The third-generation aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, are highly effective for the treatment of estrogen receptor-positive breast cancer in postmenopausal women. AIs inhibit the aromatase (CYP19A1)-mediated production of estrogens. Most patients taking AIs achieve undetectable blood estrogen concentrations resulting in drug efficacy with tolerable side effects. However, some patients have suboptimal outcomes, which may be due, in part, to inherited germline genetic variants. This review summarizes published germline genetic associations with AI treatment outcomes including systemic AI concentrations, estrogenic response to AIs, AI treatment efficacy and AI treatment toxicities. Significant associations are highlighted with commentary about prioritization for future validation to identify pharmacogenetic predictors of AI treatment outcomes that can be used to inform personalized treatment decisions in patients with estrogen receptor-positive breast cancer.

Concepts: Breast cancer, Menopause, Estrogen, Estrogen receptor, Breast, Tamoxifen, Aromatase, Aromatase inhibitor


Aim: To perform a meta-analysis of prospective, two-arm studies examining the clinical utility of using the combinatorial pharmacogenomic test, GeneSight Psychotropic, to inform treatment decisions for patients with major depressive disorder (MDD). Patients & methods: The pooled mean effect of symptom improvement and pooled relative risk ratio (RR) of response and remission were calculated using a random effect model. Results: Overall, 1556 patients were included from four studies, with outcomes evaluated at week 8 or week 10. Patient outcomes were significantly improved for patients with MDD whose care was guided by the combinatorial pharmacogenomic test results compared with unguided care (symptom improvement Δ = 10.08%, 95% CI: 1.67-18.50, p = 0.019; response RR = 1.40, 95% CI: 1.17-1.67, p < 0.001; remission RR = 1.49, 95% CI: 1.17-1.89, p = 0.001). Conclusion: GeneSight Psychotropic guided care improves outcomes among patients with MDD.


To assess patient perceptions and utilization of pharmacogenomics (PGx) testing in an integrated community health system.

Concepts: Medicine, Population health


We conducted a genome-wide association study on angiotensin-converting enzyme inhibitor-induced cough and used our dataset to replicate candidate genes identified in previous studies.

Concepts: Genetics, Cell, Bacteria, Transcription, Biology, RNA, Genome-wide association study, Swedish people


African-Americans (AA) have increased prostate cancer risk and a greater mortality rate than European-Americans (EA). AA exhibit a high prevalence of vitamin D deficiency. We examined the global prostate transcriptome in AA and EA, and the effect of vitamin D3 supplementation.

Concepts: Vitamin D, Cancer, Medical statistics, Prostate cancer, Prostate, White American, African American, English American


Warfarin dose requirement is associated with VKORC1 rs9923231, and we studied whether it is a functional variant.

Concepts: Warfarin


COVID-19 utilizes the angiotensin-converting enzyme-2 (ACE2) pathway as a means of infection. Early data on COVID-19 suggest heterogeneity in the severity of symptoms during transmission and infection ranging from no symptoms to death. The source of this heterogeneity is likely multifaceted and may have a genetic component. Demographic and clinical comorbidities associated with the severity of infection suggest that possible variants known to influence the renin-angiotensin-aldosterone system pathway (particularly those that influence ACE2) may contribute to the heterogenous infection response. ACE2 and angiotensin(1-7) (the product of ACE2) seem to have a protective effect on the pulmonary and cardiac systems. Hypertension medication modulation, may alter ACE2 and angiotensin(1-7), particularly in variants that have been shown to influence renin-angiotensin-aldosterone system function, which could be clinically useful in patients with COVID-19.