How does race and ethnicity effect the precision treatment of asthma?

ABSTRACT

Introduction: Asthma is a common condition that affects large numbers of children and adults, yet the burden of disease is not equally distributed amongst groups. In the United States, African Americans and Puerto Ricans have higher rates of asthma and its complications when compared with European Americans. However, clinical trials and genetic studies have largely focused on the latter group.

Areas covered: Here we examine what is known regarding differences in asthma treatment response by race-ethnicity. We also review existing genetic studies related to the use of asthma medications, paying special attention to studies that included substantial numbers of nonwhite population groups. Publicly accessible search engines of the medical literature were queried using combinations of the terms asthma, race, ethnicity, pharmacogenomics, and pharmacogenetics, as well as the names of individual asthma medication classes. The list of articles reviewed was supplemented by bibliographies and expert knowledge.

Expert opinion: A substantial and coordinated effort is still needed to both identify and validate genetic biomarkers of asthma medication response, as currently there are no clinically actionable genetic markers available for this purpose. The path to identifying such markers in nonwhite populations is even more formidable, since these groups are underrepresented in existing data.

KEYWORDS:

• Asthma
• pharmacogenomics
• precision medicine

Article highlights

• Existing asthma medication clinical trials and pharmacogenetic/pharmacogenomic studies are heavily skewed with disproportionate representation of white individuals of European descent.

• While limited, existing data do not convincingly support an intrinsic difference in asthma medication treatment response by race-ethnicity (e.g. Latinos, African Americans, and European Americans)

• Studies that have evaluated the association between global genetic ancestry (i.e. a person’s total proportion of ancestry from a population group) and asthma medication response are inconsistent and do not support a strong relationship. This does not exclude the possibility that individual pharmacogenetic/pharmacogenomic variants differ in magnitude or direction between population groups.

• Drug response is likely a polygenic trait. As has been found in genome-wide association studies for other traits, pharmacogenomic variants discovered in one population group often do not replicate in another. This has implications for the development of treatment response prediction algorithms (e.g. polygenetic risk scores).

• Irrespective of race-ethnicity, there are currently no clinically actionable genetic biomarkers for the precision treatment of asthma.

• The identification of novel genetic biomarkers in non-white population groups is stymied by the general lack of existing clinical trials and suitable replication populations.

Declaration of interest

L. Keoki Williams declares grant funding from the NIAID, NHLBI, and NIDDK of the U.S. National Institutes of Health. The other authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work was made possible by funding from the American Asthma Foundation, the Fund for Henry Ford Hospital, and the following institutes of National Institutes of Health: the National Institute of Allergy and Infectious Diseases (R01AI079139 to LKW), the National Heart Lung and Blood Institute (R01HL118267 and R01HL141845 to LKW), and the National Institute of Diabetes Digestive and Kidney Disorders (R01DK113003 to LKW).