1. ¹Laboratory for Gastrointestinal Diseases, SNP Research Center, RIKEN, 1-7-22 Suehiro, Tsurumi, Yokohama, Japan
2. ²Laboratory for Genetics of Allergic Diseases, SNP Research Center, RIKEN, 1-7-22 Suehiro, Tsurumi, Yokohama, Japan
3. ³Department of Preventive Medicine, Shinshu University School of Medicine, Japan
4. ⁴Department of Public Health, Jichi Medical School, Japan
5. ⁵Saitama Prefectural University, Japan
6. ⁶Division of Molecular Genetics, Department of Developmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Japan
7. ⁷Department of Pediatrics, Kawasaki Medical School, Japan
8. ⁸Department of Pediatrics, Graduate School of Medicine, Chiba University, Japan
9. ⁹Department of Pediatrics, Fukuoka University School of Medicine, Japan
10. ¹⁰Department of Oto-Rhino-Laryngology, Chiba Children's Hospital, Japan
11. ¹¹Department of Cardiology, Chiba Children's Hospital, Japan
12. ¹²Department of Pediatrics, Fuji Heavy Industries Ltd, Health Insurance Society General Ota Hospital, Japan
13. ¹³Department of Pediatrics, Yokohama Minami Kyosai Hospital, Japan
14. ¹⁴Department of Pediatrics, Seirei Yokohama Hospital, Japan
15. ¹⁵Department of Pediatrics, Keio University School of Medicine, Japan
16. ¹⁶First Department of Pediatrics, Toho University School of Medicine, Japan
17. ¹⁷Japan Kawasaki Disease Research Center, Japan
18. ¹⁸Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, the University of Tokyo, Japan
19. ¹⁹Department of Public Health, Graduate School of Medicine, Chiba University, Japan

Correspondence: Dr Y Onouchi, Laboratory for Gastrointestinal Diseases, SNP Research Center, RIKEN, 1-7-22 Suehiro, Tsurumi, Yokohama, Kanagawa 230-0045, Japan. Tel: +81 45 503 9347; Fax: +81 45 503 9346; E-mail: onouchi@src.riken.jp

Received 29 March 2004; Revised 9 July 2004; Accepted 15 July 2004; Published online 15 September 2004.

Abstract

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.