Neuroscience Letters 368 (2004) 140–143 Influence of polymorphisms in the genes for cytokines and glutathione S-transferase omega on sporadic Alzheimer’s disease Masataka Nishimura a,∗ , Toshiyo Sakamoto b , Ryuji Kaji b , Hideshi Kawakami c a Department of Neurology, Konan Hospital, Shiga 520-2433, Japan b Department of Neurology, Tokushima University School of Medicine, Tokushima 770-8503, Japan c Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Science, Hiroshima 734-8551, Japan Received 11 May 2004; received in revised form 18 June 2004; accepted 29 June 2004 Abstract We studied promoter region polymorphisms in the interleukin (IL)-1, IL-1, IL-6, IL-10, tumor necrosis factor, and transforming growth factor (TGF)-1 genes in Japanese patients with Alzheimer’s disease (AD) (n = 172) and normal controls (n = 163). We also examined an association of a polymorphism located in the glutathione S-transferase omega 1 (GSTO-1) gene region with AD patients. None of these genotypes or allele frequencies showed a significant difference between AD patients and controls. We also failed to detect any difference in the disease onset between each genotype of the seven polymorphisms. Although AD patients carrying high producer alleles of TGF-1 and IL-1 or TGF-1 and IL-6 showed a tendency for an early onset of the disease, neither of these combined effects reached a significant level after multiple comparisons. Our findings suggest that genetic polymorphisms in the cytokines and GSTO do not play a major role in Japanese AD patients. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Alzheimer’s disease; Interleukin (IL)-1; IL-6; Transforming growth factor (TGF)-1; Cytokine; Glutathione S-transferase omega (GSTO); Polymorphism Alzheimer’s disease (AD) pathology is characterized by the presence of many inflammatory proteins, including pro- inflammatory cytokines. Epidemiologic studies have also re- ported that anti-inflammatory agents may delay the onset and slow the progression of AD [14], suggesting that neuro- inflammation may play an important role in the pathogenesis of AD. Cytokine gene polymorphisms, especially in the regula- tory regions, may be related to the amount of cytokine pro- duced. Since they segregate independently, each person has an individual profile of high and low responses, which may account for individual susceptibility to inflammatory condi- tions, including AD. Indeed, high secretor alleles of inter- leukin (IL)-1, IL-1, IL-6, and transforming growth factor ∗ Corresponding author. Tel.: +81 77 589 8320; fax: +81 77 589 8321. E-mail address: ma-nishi@vmail.plala.or.jp (M. Nishimura). (TGF)-1 gene polymorphisms are shown to be associated with AD [3,12,13,17]. These results, however, have not been replicated in other groups [1,8,18]. Recently, Li et al. [10] have reported an association of a polymorphism located in the glutathione S-transferase omega-1 (GSTO-1) gene region with age-at-onset for both AD and Parkinson’s disease (PD). GSTO-1 is a stress re- sponse protein, likely involved in cellular redox homeostasis. In addition, this protein may be involved in the activation of IL-1, by inhibiting the posttranslational processing of IL-1 [9]. In the present study, we investigated whether cytokine and GSTO gene polymorphisms may be responsible, in part, for susceptibility to Japanese AD. We also examined the inter- action or combined effects among these polymorphisms. A total of 172 Japanese AD patients (103 women and 69 men; age range, 55–96 years; mean age, 77.4 ± 9.7 years) 0304-3940/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2004.06.076