Page 98 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

74 David S. Younger

100,000 children. Singh and colleagues [81] analyzed the records of children with KD <15
years in Chandigarh, North India identifying 196 children.

There was an increasing incidence of disease from 0.51 cases to 4.5 cases during the
period from 1994 to 2007. Nakamura and coworkers [82] conducted the 21st nationwide
survey of 23,730 KD children treated between 2009 and 2010 noting an annual incidence rate
of 206.2 and 239.6 per 100,000, establishing the highest rate ever for Japan in 2010. Park and
coworkers [83] surveyed Korean hospitals for the period of 2006 to 2008 identifying 9039
KD children noting an outbreak rate of 108.7 in 2006 that increased to 113.1 per 100,000 in
2008, with a mean annual incidence of 113.1 per 100,000 children.

Schiller and contributors [84] examined a national prospective study over a two year
period from 1990 to 1992 of KD children recording an annual incidence rate of 2.9 per
100,000 children younger than 16 years, and a rate of 6.2 per 100,000 children <5 years of
age. Lue [85] conducted nationwide hospital surveys of KD in Taiwan in 2006 noting an
incidence of 66.24 per 100,000 children <5 years of age representing the highest of any
preceding survey. Huang and colleagues [86] investigated the epidemiology of KD employing
national insurance claims between 2003 and 2006 noting an annual incidence of KD of 153
per 100,000 in <1 year old children with an overall incidence of 69 per 100,000 children age
<5 years. Harnden and colleagues [87] analyzed hospital admission data in England for the
period 1991 to 2000 of childhood KD identifying 2215 emergency admissions representing
an incidence that increased from 4.8 to 9.2 per 100,000 in this time period. Holman and
coworkers [88] performed a retrospective analysis of emergency childhood admission in the
United States using the Kids? Inpatient Database and a Nationwide Inpatient Sample for 2006
noting an incidence of 20.8 per 100,000 children.

Eight genome-wide association (GWAS) and linkage analysis studies of KD [89-93] have
led to susceptibility genetic loci for KD. Onouchi and colleagues [89] performed a
nonparametric GWAS of sib pairs on 75 full sib pairs, three sib trios, and one half sib,
employing Japanese criteria [71], identifying candidate gene locus at 12q24 (maximum lod
score [MLS]=2.69), with possible linkage to 4q35, 5q35, 5q34, 6q27, 7p15, 8q24, 18q23,
19q13, Xp22, and Xq27. Moreover, 90 genes were believed to be expressed in organs related
to immune function among the 128 genes that mapped within 1 lod confidence interval (CI)
of the linkage position on chromosome 12. Burgner and coworkers [90] on behalf of the
International Kawasaki Disease Genetics Consortium, investigated genetic determinants of
KD susceptibility in a GWAS of 119 Caucasian KD patients and 135 matched controls
employing the AHA criteria [72]. The investigators [90] noted associations with 40 single
nucleotide polymorphisms (SNP) and six haplotypes, however most significantly
at NAALADL2 (rs17531088) and ZRHX3 (rs7199343). The latter also known as ATBF1,
which encodes a large enhancer-binding transcription factor known to be polymorphic and
interactive with a number of proteins including protein inhibitor of activated signal transducer
and activator of transcription-3 (STAT3), is activated by interleukin (IL)-6 involved in innate
immune reactivity. The function of the N-acetylated alpha-linked acidic dipeptidase-like 2
(NAALADI2) gene, which showed the greatest change in transcript levels between acute and
convalescent KD, contributes to Cornelia de Lange syndrome, a multisystem malformation
syndrome. Tsai and coworkers [91] conducted a GWAS in a Han Chinese population in 250
KD patients and 446 controls residing in Taiwan employing the AHA criteria [72].

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