Kawasaki disease (KD) is the leading cause of acquired heart disease in children in most developed countries, including the United States. The etiology of KD is not known; however, epidemiological and immunological data suggest infectious or immune-related factors in the manifestation of the disease. Further, KD has several hereditary features that strongly suggest a genetic component to disease pathogenesis. Human leucocyte antigen (HLA) loci have also been reported to be associated with KD, but results have been inconsistent, in part, because of small study samples and varying linkage disequilibrium (LD) patterns observed across different ethnic groups. Continuing their efforts to understand genetic etiology of KD, Dr. Sadeep Shrestha, associate professor in the department of epidemiology at the University of Alabama at Birmingham, and his team imputed classical HLA I (A, B, C) and HLA II (DRB1, DQA1, DQB1) alleles in 112 White KD patients and their biological parents from North America, using SNP2HLA method from genotypes of 6700 SNPs within the extended major histocompatibility complex (MHC) region contained in the ImmunoChip. The team tested the associations of the HLA alleles with KD susceptibility using the transmission disequilibrium test (TDT). Mendelian consistency in the trios suggested high accuracy and reliability of the imputed alleles (class I = 97.5 percent; class II = 96.6 percent).

[Photo: Dr. Sadeep Shrestha]

The researchers report over-transmission of HLA-C*15 (z = +2.19, P = 0.03) and under-transmission of HLA-B*44 (z = -2.49, P = 0.01) alleles from parents to patients with KD. HLA-B*44 has been associated with KD in other smaller studies, and both HLA-C*15 and HLA-B*44 have biological mechanisms that could potentially be involved in KD pathogenesis. However, the team concluded that studies with larger sample sizes are warranted to evaluate the correlations of the strength and directions between the SNPs in MHC region and the imputed HLA alleles with KD.

The collaborative team consisted of UAB department colleagues Dr. Howard W. Wiener, statistician; Dr. Brahim Aissani, research assistant professor; and Ms. Aditi D. Shendre, graduate assistant; as well as Dr. Jianming Tang, professor in UAB’s division of infectious diseases, and Dr. Michael Portman, professor and pediatric cardiologist at Seattle Children’s Hospital.

“Imputation of Class I and II HLA Loci Using High-density SNPs from ImmunoChip and Their Associations with Kawasaki Disease in Family-based Study” was published online in March in the International Journal of Immunogenetics.

Journal article: http://www.ncbi.nlm.nih.gov/pubmed/25809546