CD40 ligand gene and Kawasaki disease.
Kawasaki disease (KD) is an acute systemic vasculitis syndrome of infants and young children. Although its etiology is largely unknown, epidemiological findings suggest that genetic factors play a role in the pathogenesis of KD. To identify genetic factors, affected sib-pair analysis has been performed. One of the identified peaks was located on the Xq26 region. A recent report of elevated expression of CD40 ligand (CD40L), which maps to Xq26, during the acute-phase KD, and its relationship to the development of coronary artery lesions (CAL) prompted us to screen for polymorphism of CD40L and to study the association of the gene to KD. A newly identified SNP in intron 4 (IVS4+121 A>G) is marginally over-represented in KD patients as compared to controls (109/602, 18.1 vs 111/737, 15.1%). When male KD patients with CAL were analyzed as a patient group, the SNP was significantly more frequent than in controls (15/58, 25.9%, vs 111/737, 15.1%, OR=2.0, 95% CI=1.07-3.66; P=0.030). Interestingly, this variation was extremely rare in a control Caucasian population (1/145, 0.7%). Our results suggest a role of CD40L in the pathogenesis of CAL and might explain the excess of males affected with KD.
Onouchi
Yoshihiro
Y
Laboratory for Gastrointestinal Diseases, SNP Research Center, RIKEN, 1-7-22 Suehiro, Tsurumi, Yokohama, Japan. onouchi@src.riken.jp
Onoue
Sakura
S
Tamari
Mayumi
M
Wakui
Keiko
K
Fukushima
Yoshimitsu
Y
Yashiro
Mayumi
M
Nakamura
Yoshikazu
Y
Yanagawa
Hiroshi
H
Kishi
Fumio
F
Ouchi
Kazunobu
K
Terai
Masaru
M
Hamamoto
Kunihiro
K
Kudo
Fumiyo
F
Aotsuka
Hiroyuki
H
Sato
Yoshitake
Y
Nariai
Akiyoshi
A
Kaburagi
Yoichi
Y
Miura
Masaru
M
Saji
Tsutomu
T
Kawasaki
Tomisaku
T
Nakamura
Yusuke
Y
Hata
Akira
A
D020413:3' Untranslated Regions; D023201:CD40 Ligand / Q000235:genetics*; D016022:Case-Control Studies; D018900:Dinucleotide Repeats; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D009080:Mucocutaneous Lymph Node Syndrome / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
D020413:3' Untranslated Regions; D023201:CD40 Ligand