Jpn. J. Infect. Dis., 58 (5), 268-271, 2005

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Original Article

Microsatellite Polymorphism in the Heme Oxygenase-1 Gene Promoter Is Associated with Susceptibility to Cerebral Malaria in Myanmar

Masato Takeda1,2, Mihoko Kikuchi3, Ratawan Ubalee3, Kesara Na-Bangchang4, Ronnatrai Ruangweerayut5, Shigeki Shibahara6, So-ichi Imai2 and Kenji Hirayama3*

1Department of Medical Zoology, Saitama Medical School, Saitama 350-0495, 2Department of Veterinary Science, Nippon Veterinary and Animal Science University, Tokyo 180-8602, 3Department of Molecular Immunogenetics, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, 6Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai 980-8575, Japan, 4Department of Clinical Pharmacology Faculty of Allied Health Sciences, Thammasat University, Rangsit Campus and and 6Mae Sot General Hospital, Tak, Thailand

(Received September 27, 2004. Accepted June 8, 2005)


*Corresponding author: Mailing address: Department of Molecular Immunogenetics, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. Tel: +81-95-849-781 8, Fax: +81-95-849-7821, E-mail: hiraken@net.nagasaki-u.ac.jp


SUMMARY: Cerebral malaria (CM) is a serious complication of Plasmodium falciparum malaria, and its pathogenesis leading to coma remains unknown. Heme oxygenase-1 (HO-1) catalyzes heme breakdown, eventually generating bilirubin, iron and carbon monoxide. The HO-1 gene promoter contains a polymorphic (GT)n repeat which may influence the expression level of HO-1. To explore the correlation between this (GT)n polymorphism and susceptibility to CM, we analyzed the frequencies of the (GT)n alleles in 120 Myanmarese patients with uncomplicated malaria (UM) and 30 patients with CM. The frequency of homozygotes for the short (GT)n alleles (<28 repeats) in CM patients was significantly higher than those in UM patinets (P < 0.008, OR = 3.14). Thus, short (GT)n alleles represent a genetic risk factor for CM.


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