ORIGINAL ARTICLE Analysis of CCG Repeats in Huntingtin Gene among HD Patients and Normal Populations in Japan Saeid Morovvati, a,b Masanori Nakagawa, b Mitsuhiro Osame, b and Ali Karami a a Research Center of Molecular Biology, Baqiyatallah Medical Sciences University, Tehran, Iran b Third Department of Internal Medicine, Kagoshima University Faculty of Medicine, Sakuragaoka, Kagoshima City, Japan Received for publication April 9, 2007; accepted June 11, 2007 (ARCMED-D-07-00146). Background. Huntington’s disease (HD) is a hereditary autosomal dominant neurodegen- erative disease characterized by motor, cognitive, and psychiatric symptoms. The molecular basis of the disease is the expansion of the trinucleotide CAG in the first exon of a gene on chromosome four (4p 16.3). There is another triplet sequence, a CCG repeat, immediately 3 0 adjacent to the CAG repeat in Huntingtin. This triplet sequence is also polymorphic, alleles of 7 or 10 repeats are predominant in populations, and strong linkage disequilibrium be- tween the CCG (7) allele and HD has been shown in western HD chromosomes, whereas Japanese HD chromosomes strongly associate with an allele of (CCG)10. Methods. Distribution of CAG and the CCG repeats in Huntingtin in 15 patients with HD living in southern Japan were selected to evaluate the regional difference in the CCG repeat number in Japan. Results. Among our 15 HD patients, only 4 patients had the (CCG)7 allele, and the (CCG)10 alleles were found in the remaining 11 patients. Conclusions. In this study, a linkage disequilibrium was found between Japanese HD chromosomes and (CCG)10, whereas western HD chromosomes are strongly associated with (CCG)7. These data suggest that (CCG)10 allele is dominant in southern Japan. Ó 2008 IMSS. Published by Elsevier Inc. Key Words: Huntington’s disease, CCG repeat, CAG repeat, Japanese population. Introduction Huntington’s disease (HD) belongs to a unique group of au- tosomal dominant progressive neurodegenerative disorders caused by the expansion of CAG trinucleotide repeats in the coding region of IT15 gene. HD alleles have O36 CAG units in the HD gene, whereas normal individuals have between 10 and 35 CAG units (1,2). HD is character- ized by uncontrolled movements (chorea), accompanied by cognitive and/or psychiatric disturbances (3). Epidemiological studies of HD report a wide variation in the prevalence rates of the disease. In the U.S. and most West- ern European countries, the prevalence is between 5 and 10 cases/100,000 individuals, whereas in African, Chinese, Jap- anese, and Finnish populations the disease is less common (4,5). Nakashima et al. reported that the prevalence of HD was 0.65/100,000 in the San-in area of Japan (6). After cloning of the Huntington’s disease mutation, two genetic polymorphisms were identified close to the CAG tract. The first one was a CCG-rich segment downstream to the (CAG)n stretch and the second one was the f2642 glutamic acid polymorphism concerning a deletion of three nucleotides at codon positions 2642e2645 (7,8). There is an interesting relationship, which is variable across major human morphological groups, between the CAG repeat numbers and another closely linked CCG repeat locus in the Huntingtin gene (9). In this respect, we studied CCG polymorphisms among Japanese Huntington patients living in southern Japan and normal populations and evaluated the relationship between Published previously online August 24, 2007. Address reprint requests to: Saeid Morovvati, MD, PhD, Assistant Professor of Human Molecular Genetics, Research Center of Molecular Biology, Baqiyatallah Medical Sciences University, Mollasadra St., Tehran, Postal Box 19945/581, Iran; E-mail: morovvati@hotmail.com or morovvat@bmsu.ac.ir 0188-4409/08 $esee front matter. Copyright Ó 2008 IMSS. Published by Elsevier Inc. doi: 10.1016/j.arcmed.2007.06.015 Archives of Medical Research 39 (2008) 131e133