Gene Expression in the Liver Holds a Clue to Disease Susceptibility in African Americans

Research has continued to show that African Americans are more likely than Whites to be more susceptible to certain diseases and to have different responses to medication. A team of researchers working on a project funded by NIMHD wondered if the strength of this association is related to ancestry. To answer this question, they studied gene expression profiles in liver cells of African Americans with West African ancestry (WAA). The researchers focused on genes that are specifically involved in drug metabolism. They found that the amount of WAA that a person has determines how much certain genes are expressed in their liver cells. Some of those unique patterns of expression reduce their ability to break down certain drugs and increase susceptibility to certain diseases.

The researchers first obtained liver cell samples that originally came from 60 African Americans with WAA. They identified 131 genes (DNA sequences) in these cells that had a pattern of expression unique to this population. They also looked at expression of these genes in other sets of samples from 38 African Americans with WAA and 183 European Americans. The researchers noted that lower numbers of methyl groups in the DNA of WAA samples caused these genes to have more pronounced effects. Methyl groups in the DNA turn genes on and off, like a light. Lower numbers of methyl groups in people with WAA make them prone to heart disease, diabetes, inflammatory disease, kidney disease, and cancer.

The researchers also identified five genes in the liver cells with expression patterns that made people with WAA less responsive to medicines. For example, expression of the CYP2C19 gene, which helps break down drugs in the liver, became half its original level for one-fold increase in WAA characteristics. The expression of the P2RY1 gene, which causes blood clotting disorders when expressed in higher than normal levels, increased more than one and half times for one-fold increase in WAA characteristics.

The study highlights how disease susceptibility and response to certain drugs might not be the same for all populations.

Citation:
Park, C.S., De, T., Xu, Y., Zhong, Y., Smithberger, E., Alarcon, C., ……Perera, M.A. (2019). Hepatocyte gene expression and DNA methylation as ancestry-dependent mechanisms in African Americans. NPJ Genomic Medicine. Nov 25;4:29. https://doi.org/10.1038/s41525-019-0102-y.

Page updated January 14, 2022