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Concordance of Genotypes in Pre– and Post–Lung Transplantation DNA Samples

Channing Laboratory and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital; and Harvard Medical School, Boston, Massachusetts

Correspondence and requests for reprints should be addressed to Dawn L. DeMeo, M.D., M.P.H., Channing Laboratory, 181 Longwood Ave., Boston, MA 02115. E-mail: redld{at}channing.harvard.edu

Genetic epidemiology studies of end-stage lung disease are potentially hindered by low numbers of participants due to early death of patients from the underlying disease, or due to exclusion from studies after patients have had lung transplants, because of concern about bias of genotype data due to chimerism. The number of participants enrolled in genetic studies of end-stage lung disease could be increased by including those individuals who have undergone lung transplant. We hypothesized that individuals who have had lung transplants can be included in genetic epidemiology studies that use single nucleotide polymorphism and short tandem repeat marker data, without confounding due to chimerism. Ten probands with severe, early-onset chronic obstructive pulmonary disease were included in this analysis. Pre– and post–lung transplant DNA samples were used in the investigation of concordance of genotype results for 12 short tandem repeat markers and 23 single nucleotide polymorphisms. Concordance was observed for all genotypes before and after lung transplant. We conclude that the risk of biasing genetic epidemiology studies due to donor lung–related DNA microchimerism is low, and that the inclusion of post–lung transplantation participants will allow for larger genetic epidemiology studies of individuals with end-stage lung disease.

Key Words: genetic epidemiology • lung • chimerism • transplantation