Gene Expression Affected by African Ancestry
A new study by Northwestern Medicine has become the first to compare gene expression levels in African American populations by studying the levels of mRNA expressed in the liver. Previous studies have compared only African and European individuals separately and this study aimed to address the “grey” area of mixed ethnicities.
The study involved isolating and culturing primary hepatocytes, the major cell type in the liver that metabolises drugs, from 60 African Americans and examining the levels of mRNA present. The levels of mRNA in the liver are indicative of the amount of a protein present, which is important as proteins play many critical roles in the body.
African Americans have varying proportions of African and European ancestry and are under-represented in genetic databases. There is growing significance being placed on how genetic findings are interpreted in “admixed” populations such as African Americans and Hispanic Americans. Compared to other populations, some chronic diseases disproportionately affect African Americans, such as type 2 Diabetes. There are also reports on adverse reactions to some drugs, whilst conversely, they may be naturally protected from certain conditions such as Alzheimer’s disease. The study could offer information on responses to medication and the real risk of diseases within this group.
Results showed at least 28 genes with varied levels of mRNA that correlated with the amount of African ancestry an individual had. These genes were linked to 220 clinical diseases such as coronary heart disease, as well as higher levels of triglycerides leading to liver and pancreas problems. One of the genes was CYP2C19, which plays a role in drug metabolism and was found to be decreased in individuals with higher levels of African ancestry. This highlights the need for further research into drug efficacy and toxicity variation in African American populations. Other genes were VGEF, a target for cancer therapy, and APOL1 in renal disease, both of which were found to be increased in individuals with higher African ancestry.
The study will be important in understanding health disparities in African Americans and provides a starting database for future investigations to build upon. Increased representation of all ethnicities, in addition to diversity in age, sex, and socioeconomic background in cohort selection for population sequencing is required to allow equitable access to the advances of personalised medicine.