A Genome-Wide Association Study Identifies Novel and Functionally Related Susceptibility Loci for Kawasaki Disease

Burgner, David; Dávila, Sonia; Breunis, Willemijn B.; Ng, Sarah; Li, Yang; Bonnard, Carine; Ling, Ling; Wright, Victoria J.; Thalamuthu, Anbupalam; Odam, Miranda; Shimizu, Chisato; Burns, Jane C.; Levin, Michael; Kuijpers, Taco W.; Hibberd, Martin L.

doi:10.1371/journal.pgen.1000319

Cited by 240 publications

(181 citation statements)

References 59 publications

(85 reference statements)

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“…Forty SNPs and six haplotypes were confirmed in an independent cohort of KD families [71] . This insightful work led to the identification of a SNP within the N-acetylated alpha-linked acidic dipeptidase-like 2 gene (NAALADL2; rs17531088), which was significantly associated with the susceptibility to KD.…”

Section: Genome-wide Association Study (Gwas) In Kawasaki Diseasementioning

confidence: 89%

Genetic polymorphisms in Kawasaki disease

Kuo

Chang²

2011

Acta Pharmacol Sin

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Kawasaki disease (KD) is an acute febrile systemic vasculitis, and the cause of KD is not well understood. It is likely due to multiple interactions between genes and environmental factors. The development of genetic association and genome-wide association studies (GWAS) has opened an avenue to better understanding the molecular mechanisms underlying KD. A novel ITPKC signaling pathway was recently found to be responsible for the susceptibility to KD. Furthermore, the GWAS demonstrated the functionally related susceptibility loci for KD in the Caucasian population. In the last decade, the identification of several genomic regions linked to the pathogenesis of KD has made a major breakthrough in understanding the genetics of KD. This review will focus on genetic polymorphisms associated with KD and describe some of the possible clinical implications and molecular mechanisms that can be used to explain how genetic variants regulate the pathogenesis in KD.

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Section: Genome-wide Association Study (Gwas) In Kawasaki Diseasementioning

confidence: 89%

Genetic polymorphisms in Kawasaki disease

Kuo

Chang²

2011

Acta Pharmacol Sin

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“…Genome-wide association study for KD was firstly performed by Burgner et al (27). A total of 40 SNPs and 6 haplotypes were confirmed in an independent cohort of KD families.…”

Section: Discussionmentioning

confidence: 99%

TARC/CCL17 gene polymorphisms and expression associated with susceptibility and coronary artery aneurysm formation in Kawasaki disease

et al. 2013

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Background: Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. Thymus and activation-regulated chemokine/chemokine ligand 17 (TARC/CCL17) is one of the Th2 chemokines and has been suggested as a candidate gene for conferring susceptibility to Th2 associated with allergy diseases. This study examined the correlation between gene polymorphisms and plasma levels of TARC/CCL17 in patients with KD and the outcomes of KD. Methods: A total of 381 KD patients and 564 controls were subjected to determination of five tagging single-nucleotide polymorphisms of TARC/CCL17. In addition, plasma TARC/ CCL17 levels were measured by enzyme-linked immunosorbent assay. results: Polymorphisms of TARC/CCL17 were significantly different between normal children and patients with KD. A allele of rs4784805 has better intravenous immunoglobulin (IVIG) treatment response to KD. Furthermore, plasma TARC/ CCL17 levels were higher in KD patients than that in controls before IVIG treatment. After IVIG treatment, plasma TARC/ CCL17 levels decreased significantly. conclusion: This study provides the first evidence supporting the association between TARC/CCL17 polymorphisms, susceptibility of KD, and IVIG responses in KD patients. k awasaki disease (KD), also known as mucocutaneous lymph node syndrome, is an acute febrile systemic vasculitis that was first described by Kawasaki et al. in 1974 in English (1), but its etiology remains unknown till now. It occurs most commonly in children younger than 5 y of age, particularly in children younger than 2 y of age, and the clinical presentation of KD is prolonged fever, conjunctivitis, diffuse mucosal inflammation, polymorphous skin rashes, indurative edema of the hands and feet associated with peeling of finger tips, and nonsuppurative lymphadenopathy (2). In developed countries, KD has been the leading cause of acquired heart diseases in children (2,3). The most serious complication of KD is the occurrence of coronary artery lesions (CALs), including myocardial infarction, coronary artery fistula formation (4), coronary artery dilation, or coronary artery aneurysm (CAA) (5). In addition, KD is the major cause of acquired CAA in childhood (6). The prevalence of KD in children is the highest in Japan, followed by Korea and Taiwan, and the lowest in Europe (5). Therefore, it is possible that a genetic background plays an important role in the pathogenesis of KD.Thymus and activation-regulated chemokine/chemokine ligand 17 (TARC/CCL17) is a member of the CC chemokine group (7). It is a ligand of the CC chemokine receptor (8), which is selectively expressed on Th2 cells (9) and serves for the recruitment and migration of cells bearing this receptor (7-9). TARC/CCL17 has been suggested as a candidate gene for conferring susceptibility to Th2 associated with allergy diseases and is highly implicated in the pathogenesis of atopic dermatitis (10,11) and bronchial asthma (12). There are several lines of evidence pointing out an abnormal Th1/Th2 balance in KD patients (13). Recently, it has b...

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“…7 10 5 ). CSMD1 is a complement regulatory protein that blocks the classical but not alternate complement pathway 20) and is associated with Kawasaki disease 21) . Interestingly, recently, it was reported that SNPs in the CSMD1 gene are also associated with metabolic syndrome 22) and hypertension 23) .…”

Section: Discussionmentioning

confidence: 99%

Identification of Evidence Suggestive of an Association with Peripheral Arterial Disease at the OSBPL10 Locus by Genome-Wide Investigation in the Japanese Population

Kuroda

Nakagami

Katsuya

et al. 2010

JAT

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Aim: Peripheral arterial disease (PAD) is a common cause of cardiovascular morbidity and an independent predictor of cardiovascular mortality. However, little is known about the genetic basis of PAD. To elucidate this, we performed a two-staged genome-wide association study in Japanese individuals. Methods: We initially tested 222,285 single-nucleotide polymorphisms (SNPs). After the first screening in a panel of 195 PAD cases and 1,358 controls, 2,696 SNPs (1.2%) were further genotyped in the second screening using another panel of 699 PAD cases and 1540 controls. In both screenings, controls were subjects affected with some diseases other than PAD. Results: When analyzed in the combined panel, the strongest signal of PAD association was observed at rs1902341 in the intron of OSBPL10 (p 4.7E-7 for trend test; OR 1.31, 95% CI 1.18 − 1.46). Also, PAD was modestly associated at several other loci such as rs2554503 in CSMD1 (p 5.7E-5; OR 1.32, 95% CI 1.15 − 1.51) or rs235243 in VSP13D (p 0.04; OR 1.18, 95% CI 1.01 − 1.37). Conclusion: Our genome-wide exploration identified suggestive evidence of PAD association at the OSBPL10 locus. Because the association has not reached a genome-wide significant level, further replication study is warranted for verification in the Japanese population.

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A Genome-Wide Association Study Identifies Novel and Functionally Related Susceptibility Loci for Kawasaki Disease

Cited by 240 publications

References 59 publications

Genetic polymorphisms in Kawasaki disease

Genetic polymorphisms in Kawasaki disease

TARC/CCL17 gene polymorphisms and expression associated with susceptibility and coronary artery aneurysm formation in Kawasaki disease

Identification of Evidence Suggestive of an Association with Peripheral Arterial Disease at the OSBPL10 Locus by Genome-Wide Investigation in the Japanese Population

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