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2015 ; 42
(3
): 140-6
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Imputation of class I and II HLA loci using high-density SNPs from ImmunoChip and
their associations with Kawasaki disease in family-based study
#MMPMID25809546
Shrestha S
; Wiener HW
; Aissani B
; Shendre A
; Tang J
; Portman MA
Int J Immunogenet
2015[Jun]; 42
(3
): 140-6
PMID25809546
show ga
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. To maximize the informativeness of single nucleotide
polymorphism (SNP) genotypes in the major histocompatibility (MHC) region, we
imputed classical HLA I (A, B, C) and HLA II (DRB1, DQA1, DQB1) alleles using
SNP2HLA method from genotypes of 6700 SNPs within the extended MHC region
contained in the ImmunoChip among 112 White patients with KD and their biological
parents from North America and tested their association with KD susceptibility
using the transmission disequilibrium test. Mendelian consistency in the trios
suggested high accuracy and reliability of the imputed alleles (class I = 97.5%,
class II = 96.6%). While several SNPs in the MHC region were individually
associated with KD susceptibility, we 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. Overall, inferring HLA loci
within the same ethnic group, using family-based information is a powerful
approach. However, 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.
|*Genetic Association Studies
[MESH]
|*Genetic Predisposition to Disease
[MESH]
|*Polymorphism, Single Nucleotide
[MESH]
|Alleles
[MESH]
|Family
[MESH]
|Female
[MESH]
|Gene Frequency
[MESH]
|Histocompatibility Antigens Class I/*genetics/immunology
[MESH]
|Histocompatibility Antigens Class II/*genetics/immunology
[MESH]