Apolipoprotein E promoter polymorphism and sporadic Alzheimer’s disease in a Japanese population Hiromasa Toji a , Hirofumi Maruyama a , Ken Sasaki b , Shigenobu Nakamura a , Hideshi Kawakami a, * a Third Department of Internal Medicine, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-Ku, Hiroshima 734-8551, Japan b Kinoko Espoir Hospital, Kasaoka, Okayama 714-0071, Japan Received 13 October 1998; accepted 23 October 1998 Abstract A recent observation has shown that a common polymorphism (-491 A) in the promoter of apolipoprotein E (APOE) was associated with an increased risk for Alzheimer’s disease (AD) in European decent. Moreover, the promoter with -491 A showed higher transcriptional activity than that with -491 T. To investigate the further contribution of the polymorphism to the etiology of sporadic AD, we evaluated associations between Japanese AD and -491 A/T polymorphism of APOE. There was no significant difference between these cases and controls. The percentage of the homozygote of -491 A allele (AA) among the Japanese control population was significantly higher than that among the Spanish control population. The APOE promoter genotype frequencies may be influenced by the ethnic background. Our study failed to confirm any relationship between -491 A/T polymorphism and AD. Thus, we conclude that the APOE promoter polymorphism does not represent an additional risk factor for AD in Japanese populations.  1999 Elsevier Science Ireland Ltd. All rights reserved Keywords: Apolipoprotein E promoter polymorphism; Risk factor; Alzheimer’s disease; Ethnic background The cause or risk factors of Alzheimer’s disease (AD) have not been fully elucidated. A significant portion of patients with the disease clearly demonstrates genetic sus- ceptibility. The APOE4 genotype is a closely related genetic factor for late-onset AD [3]. Other genetic factors within the APOE gene region may be associated with the development of AD. Bullido reported that homozygosity of a common variant (-491A) in the APOE promoter region is associated with increased risk of AD in Spanish and North American subjects and that the association is independent of APOE4 status [1]. Furthermore, the -491A allele was exhibited with higher constitutive levels of APOE promoter activity than the -491T allele. Taken together, they suggested that -491A allele may directly contribute to risk of developing AD through the promoter efficiency. Thus, we investigated the biallelic polymorphism (-491 A/T) frequency of the gene in a Japanese population. The subjects consisted of 118 Japanese patients with sporadic AD (age at onset 67.6 ± 9.5 years; mean ± SD, male 34, female 84) and 118 healthy age-matched controls (age at examination 65.1 ± 8.5 years; male 31, female 87). The diagnosis of probable AD was based on clinical find- ings, according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) cri- teria. Genomic DNA was prepared from peripheral white blood cells using standard phenol extraction. APOE genotyping was performed as previously reported [4]. For APOE pro- moter genotyping, the DNA was amplified by polymerase chain reaction (PCR) using oligonucleotide primers forward (5′-AGACAGTCTCCCTCTTGCTGA-3′) and reverse (5′- CCTCCTTTCCTGACCCTGTCCTT-3′). The amplified PCR product (3 ml) was transferred to membranes and Neuroscience Letters 259 (1999) 56–58 0304-3940/99/$ - see front matter  1999 Elsevier Science Ireland Ltd. All rights reserved PII S0304-3940(98)00855-6 * Corresponding author. Tel.: +81 82 2575201; fax: +81 82 5050490; e-mail: hkawakam@ipc.hiroshima-u.ac.jp