Abstract 13626: Human Leukocyte Antigen A*30 is Associated With Congenital Heart Disease

Abstract

Introduction: Congenital heart disease (CHD) arises from many etiologies, ranging from genetic to environmental exposures, such as viral infections. The human leukocyte antigens (HLA) play an important role in the immune response to pathogens. HLA has been extensively explored and linked with several diseases; no such investigations, however, have been done in context of CHD. Hypothesis: We sought to identify potential HLA associations with CHD in a large population sample with molecular-based HLA typing. Methods: Available data on race, gender, HLA-A, B, and DRB1 typing (1-field, antigen level) was collected from the 2,349 patients in the United Network for Organ Sharing (UNOS) database undergoing heart transplant due to CHD between 2005 and 2017. These were compared to all 80,893 deceased kidney donors in the same period. Nominal variables were compared with Pearson’s chi-square, and logistic regression was used to compare all HLA antigens between groups, adjusting for race and gender. The false discovery rate was used to control for multiple comparisons, with adjusted p-values <0.05 considered significant. Results: There were 14 HLA-A, 25 HLA-B, and 14 HLA-DRB1 antigens with an overall frequency of 1% or higher. The frequency of HLA-A*30, B*44, and DRB1*08 differed significantly between groups (Table 1). Unconditional regression showed significantly increased odds of CHD in patients with HLA-A*30 and HLA-DRB1*08, as well as significantly lower odds in those with HLA-B*44 (Table 1). The demographics between groups were comparable, with the exception of fewer Caucasians in the cases (CHD 60.7% vs controls 65.6%, p=0.026). When adjusted for race and gender, only HLA-A*30 remained statistically significant. Conclusions: HLA-A*30 appears to be linked with CHD independent of race. Further analyses with detailed CHD diagnoses and high-resolution HLA typing data are needed to explore potential associations between specific cardiac defects and HLA at the allele level.