Association of CCR2-CCR5 haplotypes and CCL3L7 copy number with kawasaki disease, coronary artery lesions, and IVIG responses in Japanese children

Manju Mamtani, Tomoyo Matsubara, Chisato Shimizu, Susumu Furukawa, Teiji Akagi, Yoshihiro YOnouchi, Akira Hata, Akihiro Fujino, Weijing He, Sunil K. Ahuja, Jane C. Burns

Research output: Contribution to journalArticle

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Abstract

Background: The etiology of Kawasaki Disease (KD) is enigmatic, although an infectious cause is suspected. Polymorphisms in CC chemokine receptor 5 (CCR5) and/or its potent ligand CCL3L1 influence KD susceptibility in US, European and Korean populations. However, the influence of these variations on KD susceptibility, coronary artery lesions (CAL) and response to intravenous immunoglobulin (IVIG) in Japanese children, who have the highest incidence of KD, is unknown. Methodology/Principal Findings: We used unconditional logistic regression analyses to determine the associations of the copy number of the CCL3L1 gene-containing duplication and CCR2-CCR5 haplotypes in 133 Japanese KD cases [33 with CAL and 25 with resistance to IVIG] and 312 Japanese controls without a history of KD. We observed that the deviation from the population average of four CCL3L1 copies (i.e., < or > four copies) was associated with an increased risk of KD and IVIG resistance (adjusted odds ratio (OR) =2.25, p = 0.004 and OR = 6.26, p = 0.089, respectively). Heterozygosity for the CCR5 HHF*2 haplotype was associated with a reduced risk of both IVIG resistance (OR = 0.21, p = 0.026) and CAL development (OR = 0.44, p = 0.071). Conclusions/Significance: The CCL3L1-CCR5 axis may play an important role in KD pathogenesis. In addition to clinical and laboratory parameters, genetic markers may also predict risk of CAL and resistance to IVIG.

Original languageEnglish
Article numbere11458
JournalPLoS One
Volume5
Issue number7
DOIs
Publication statusPublished - 2010
Externally publishedYes

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CCR5 Receptors
Mucocutaneous Lymph Node Syndrome
Intravenous Immunoglobulins
immunoglobulins
Haplotypes
coronary vessels
Coronary Vessels
haplotypes
odds ratio
Odds Ratio
disease resistance
Disease Susceptibility
disease incidence
etiology
heterozygosity
pathogenesis
Gene Duplication
CCR5 receptor
coronary artery disease
genetic polymorphism

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Association of CCR2-CCR5 haplotypes and CCL3L7 copy number with kawasaki disease, coronary artery lesions, and IVIG responses in Japanese children. / Mamtani, Manju; Matsubara, Tomoyo; Shimizu, Chisato; Furukawa, Susumu; Akagi, Teiji; YOnouchi, Yoshihiro; Hata, Akira; Fujino, Akihiro; He, Weijing; Ahuja, Sunil K.; Burns, Jane C.

In: PLoS One, Vol. 5, No. 7, e11458, 2010.

Research output: Contribution to journalArticle

Mamtani, M, Matsubara, T, Shimizu, C, Furukawa, S, Akagi, T, YOnouchi, Y, Hata, A, Fujino, A, He, W, Ahuja, SK & Burns, JC 2010, 'Association of CCR2-CCR5 haplotypes and CCL3L7 copy number with kawasaki disease, coronary artery lesions, and IVIG responses in Japanese children', PLoS One, vol. 5, no. 7, e11458. https://doi.org/10.1371/journal.pone.0011458
Mamtani, Manju ; Matsubara, Tomoyo ; Shimizu, Chisato ; Furukawa, Susumu ; Akagi, Teiji ; YOnouchi, Yoshihiro ; Hata, Akira ; Fujino, Akihiro ; He, Weijing ; Ahuja, Sunil K. ; Burns, Jane C. / Association of CCR2-CCR5 haplotypes and CCL3L7 copy number with kawasaki disease, coronary artery lesions, and IVIG responses in Japanese children. In: PLoS One. 2010 ; Vol. 5, No. 7.
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AU - Mamtani, Manju

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AU - Shimizu, Chisato

AU - Furukawa, Susumu

AU - Akagi, Teiji

AU - YOnouchi, Yoshihiro

AU - Hata, Akira

AU - Fujino, Akihiro

AU - He, Weijing

AU - Ahuja, Sunil K.

AU - Burns, Jane C.

PY - 2010

Y1 - 2010

N2 - Background: The etiology of Kawasaki Disease (KD) is enigmatic, although an infectious cause is suspected. Polymorphisms in CC chemokine receptor 5 (CCR5) and/or its potent ligand CCL3L1 influence KD susceptibility in US, European and Korean populations. However, the influence of these variations on KD susceptibility, coronary artery lesions (CAL) and response to intravenous immunoglobulin (IVIG) in Japanese children, who have the highest incidence of KD, is unknown. Methodology/Principal Findings: We used unconditional logistic regression analyses to determine the associations of the copy number of the CCL3L1 gene-containing duplication and CCR2-CCR5 haplotypes in 133 Japanese KD cases [33 with CAL and 25 with resistance to IVIG] and 312 Japanese controls without a history of KD. We observed that the deviation from the population average of four CCL3L1 copies (i.e., < or > four copies) was associated with an increased risk of KD and IVIG resistance (adjusted odds ratio (OR) =2.25, p = 0.004 and OR = 6.26, p = 0.089, respectively). Heterozygosity for the CCR5 HHF*2 haplotype was associated with a reduced risk of both IVIG resistance (OR = 0.21, p = 0.026) and CAL development (OR = 0.44, p = 0.071). Conclusions/Significance: The CCL3L1-CCR5 axis may play an important role in KD pathogenesis. In addition to clinical and laboratory parameters, genetic markers may also predict risk of CAL and resistance to IVIG.

AB - Background: The etiology of Kawasaki Disease (KD) is enigmatic, although an infectious cause is suspected. Polymorphisms in CC chemokine receptor 5 (CCR5) and/or its potent ligand CCL3L1 influence KD susceptibility in US, European and Korean populations. However, the influence of these variations on KD susceptibility, coronary artery lesions (CAL) and response to intravenous immunoglobulin (IVIG) in Japanese children, who have the highest incidence of KD, is unknown. Methodology/Principal Findings: We used unconditional logistic regression analyses to determine the associations of the copy number of the CCL3L1 gene-containing duplication and CCR2-CCR5 haplotypes in 133 Japanese KD cases [33 with CAL and 25 with resistance to IVIG] and 312 Japanese controls without a history of KD. We observed that the deviation from the population average of four CCL3L1 copies (i.e., < or > four copies) was associated with an increased risk of KD and IVIG resistance (adjusted odds ratio (OR) =2.25, p = 0.004 and OR = 6.26, p = 0.089, respectively). Heterozygosity for the CCR5 HHF*2 haplotype was associated with a reduced risk of both IVIG resistance (OR = 0.21, p = 0.026) and CAL development (OR = 0.44, p = 0.071). Conclusions/Significance: The CCL3L1-CCR5 axis may play an important role in KD pathogenesis. In addition to clinical and laboratory parameters, genetic markers may also predict risk of CAL and resistance to IVIG.

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