Hello all! The Bioethics Panel is tomorrow at 7:00 PM. You can join the Webex session at that time through this website's home page!
Earlier, we discussed one of Dr. Shuldiner’s (a presenter at the event tomorrow) research papers. Here is a short summary of Dr. Amber Beitelshees’s study regarding the adverse effects of hydrochlorothiazide (HCTZ), a drug given to patients who experience hypertension (also called high blood pressure), which is a risk factor for stroke, cardiovascular disease and kidney diseases. This drug is prescribed to about a 100 million Americans per year, but is know to have adverse metabolic effects like hyperglycemia.
In this study Dr. Beitelshees and associates collected phenotype and genotype data from previous studies to identify whether the intake of HCTZ by certain patients with certain genotypes would produce an adverse effect on their glucose and triglyceride levels. The analysis was done by race, meaning the data was separated into two classes; data that came from African American participants and data that came from European-American participants.
The results suggested that HCTZ significantly increased glucose and triglyceride levels in both races. In African Americans, two single nucleotide polymorphisms (SNPs, these are locations in a chromosome where different versions of the chromosome have different nucleotides) were correlated with increasing the triglyceride levels when the participant takes HCTZ. These two SNPs were in the NELL1 gene, which encodes a protein involved in fat cell differentiation. No SNPs achieved a strong enough correlation with European Americans. In the end, Dr. Beitelshees and her associates proposed that HCTZ could be modulating fat cell differentiation through its interactions with the NELL1 gene. This leads to accumulation of plasma triglycerides in susceptible patients. The magnitude of the affect caused by HCTZ is labelled as “clinically relevant”.
Also, there will figures from the article posted on our Instagram account soon that display data derived from the study.
We'll see you this Friday!
The article: Del-Aguila, J. L., Beitelshees, A. L., Cooper-Dehoff, R. M., Chapman, A. B., Gums, J. G., Bailey, K., Gong, Y., Turner, S. T., Johnson, J. A., & Boerwinkle, E. (2014). Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans. The pharmacogenomics journal, 14(1), 35–40. https://doi.org/10.1038/tpj.2013.3
Background information: Carm, S.F.K.Q.L.A.M.B.G.P.E.T. J. (2016). Biological Science. [VitalSource Bookshelf]. Retrieved from https://bookshelf.vitalsource.com/#/books/9780134254166/