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Friday, January 3, 2014

Implications of race and ethnicity on genetic profiles for personalized medicine

It is well known that frequencies and severity of disease can differ among races.  The mixing of African, European, and Native American ancestries has resulted in a variety of different ethnic groups with varied diversity. There is robust evidence from various clinical trials that different ethnic groups have variable responses to specific therapeutic agents.  The study of pharmacogenetics is used to personalize therapies specific to individuals from different ethnic or racial groups and it has historically been composed of mostly non-Hispanic whites of European descent. 

Ortega and Meyers summarize the genetic and epidemiologic basis for the variable genetic backgrounds observed between different, recently admixed ethnic groups such as African American or Hispanic (J Allergy Clin Immunol 2014; 133(1): 16-26). Rare genetic variants appear to be more frequent among individuals of African ancestry and could account for inter-ethnic differences in drug responses especially for rare, adverse events. Variability in phenotypes important in determining asthma severity between different ethnic groups could impact therapeutic responses to commonly used therapies.  For example, individuals with higher degrees of African ancestry have lower baseline lung function and increased risk for asthma exacerbations . In addition, African Americans are an ethnic group with an increased risk for adverse, possibly life-threatening, responses to long acting B2-adrenergic receptor agonists compared to non-Hispanic whites. 

The authors go on to explain that the genetic complexity of admixed ethnic groups is further challenged by representing only a minority of subjects enrolled in studies, cultural and habitual differences, and increased genetic diversity at an individual level.  These complex variables will require a combination of methods including genome-wide association studies, admixture-based analytical methods, and next-generation sequencing in larger populations to find and study genetic differences among ethnic groups and contribute to future pharmacogenetic studies.  

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