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Association of an IGHV3-66 gene variant with Kawasaki disease.
- Source :
-
Journal of human genetics [J Hum Genet] 2021 May; Vol. 66 (5), pp. 475-489. Date of Electronic Publication: 2020 Oct 26. - Publication Year :
- 2021
-
Abstract
- In a meta-analysis of three GWAS for susceptibility to Kawasaki disease (KD) conducted in Japan, Korea, and Taiwan and follow-up studies with a total of 11,265 subjects (3428 cases and 7837 controls), a significantly associated SNV in the immunoglobulin heavy variable gene (IGHV) cluster in 14q33.32 was identified (rs4774175; OR = 1.20, P = 6.0 × 10 <superscript>-9</superscript> ). Investigation of nonsynonymous SNVs of the IGHV cluster in 9335 Japanese subjects identified the C allele of rs6423677, located in IGHV3-66, as the most significant reproducible association (OR = 1.25, P = 6.8 × 10 <superscript>-10</superscript> in 3603 cases and 5731 controls). We observed highly skewed allelic usage of IGHV3-66, wherein the rs6423677 A allele was nearly abolished in the transcripts in peripheral blood mononuclear cells of both KD patients and healthy adults. Association of the high-expression allele with KD strongly indicates some active roles of B-cells or endogenous immunoglobulins in the disease pathogenesis. Considering that significant association of SNVs in the IGHV region with disease susceptibility was previously known only for rheumatic heart disease (RHD), a complication of acute rheumatic fever (ARF), these observations suggest that common B-cell related mechanisms may mediate the symptomology of KD and ARF as well as RHD.
- Subjects :
- Adult
Alleles
B-Lymphocytes metabolism
Computer Simulation
Datasets as Topic
Follow-Up Studies
Gene Expression Regulation
Genetic Predisposition to Disease
High-Throughput Nucleotide Sequencing
Humans
Japan epidemiology
Leukocytes metabolism
Linkage Disequilibrium
Models, Genetic
Mucocutaneous Lymph Node Syndrome epidemiology
Polymorphism, Single Nucleotide
Republic of Korea epidemiology
Taiwan epidemiology
Transcription, Genetic
Genes, Immunoglobulin Heavy Chain
Genome-Wide Association Study
Mucocutaneous Lymph Node Syndrome genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1435-232X
- Volume :
- 66
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of human genetics
- Publication Type :
- Academic Journal
- Accession number :
- 33106546
- Full Text :
- https://doi.org/10.1038/s10038-020-00864-z