TY - JOUR
T1 - The regulation of soluble receptor for AGEs contributes to carbonyl stress in schizophrenia
AU - Miyashita, Mitsuhiro
AU - Watanabe, Takuo
AU - Ichikawa, Tomoe
AU - Toriumi, Kazuya
AU - Horiuchi, Yasue
AU - Kobori, Akiko
AU - Kushima, Itaru
AU - Hashimoto, Ryota
AU - Fukumoto, Motoyuki
AU - Koike, Shinsuke
AU - Ujike, Hiroshi
AU - Arinami, Tadao
AU - Tatebayashi, Yoshitaka
AU - Kasai, Kiyoto
AU - Takeda, Masatoshi
AU - Ozaki, Norio
AU - Okazaki, Yuji
AU - Yoshikawa, Takeo
AU - Amano, Naoji
AU - Washizuka, Shinsuke
AU - Yamamoto, Hiroshi
AU - Miyata, Toshio
AU - Itokawa, Masanari
AU - Yamamoto, Yasuhiko
AU - Arai, Makoto
N1 - Funding Information:
We especially thank Hiroko Yuzawa at the Institute of Medical Sciences, Tokai University for the measurement of plasma pentosidine levels. We are also grateful for the expert technical assistance of Izumi Nohara, Mayumi Arai, and Nanako Obata. We appreciate the contributions of Yuuki Yoshida and Ikuyo Kito who offered technical advice and assisted with the preparation of this manuscript. This work was supported by JSPS KAKENHI Grant Numbers JP23791368 , JP16H05380 , JP25861040 and JP25253074 .
Publisher Copyright:
© 2016 The Authors
PY - 2016/10/21
Y1 - 2016/10/21
N2 - Our previous study showed that enhanced carbonyl stress is closely related to schizophrenia. The endogenous secretory receptor for advanced glycation end-products (esRAGE) is a splice variant of the AGER gene and is one of the soluble forms of RAGE. esRAGE is considered to be a key molecule for alleviating the burden of carbonyl stress by entrapping advanced glycation end-products (AGEs). In the current study, we conducted genetic association analyses focusing on AGER, in which we compared 212 schizophrenic patients to 214 control subjects. We also compared esRAGE levels among a subgroup of 104 patients and 89 controls and further carried out measurements of total circulating soluble RAGE (sRAGE) in 25 patients and 49 healthy subjects. Although the genetic association study yielded inconclusive results, multiple regression analysis indicated that a specific haplotype composed of rs17846798, rs2071288, and a 63 bp deletion, which were in perfect linkage disequilibrium (r2 = 1), and rs2070600 (Gly82Ser) were significantly associated with a marked decrease in serum esRAGE levels. Furthermore, compared to healthy subjects, schizophrenia showed significantly lower esRAGE (p = 0.007) and sRAGE (p = 0.03) levels, respectively. This is the first study to show that serum esRAGE levels are regulated by a newly identified specific haplotype in AGER and that a subpopulation of schizophrenic patients are more vulnerable to carbonyl stress.
AB - Our previous study showed that enhanced carbonyl stress is closely related to schizophrenia. The endogenous secretory receptor for advanced glycation end-products (esRAGE) is a splice variant of the AGER gene and is one of the soluble forms of RAGE. esRAGE is considered to be a key molecule for alleviating the burden of carbonyl stress by entrapping advanced glycation end-products (AGEs). In the current study, we conducted genetic association analyses focusing on AGER, in which we compared 212 schizophrenic patients to 214 control subjects. We also compared esRAGE levels among a subgroup of 104 patients and 89 controls and further carried out measurements of total circulating soluble RAGE (sRAGE) in 25 patients and 49 healthy subjects. Although the genetic association study yielded inconclusive results, multiple regression analysis indicated that a specific haplotype composed of rs17846798, rs2071288, and a 63 bp deletion, which were in perfect linkage disequilibrium (r2 = 1), and rs2070600 (Gly82Ser) were significantly associated with a marked decrease in serum esRAGE levels. Furthermore, compared to healthy subjects, schizophrenia showed significantly lower esRAGE (p = 0.007) and sRAGE (p = 0.03) levels, respectively. This is the first study to show that serum esRAGE levels are regulated by a newly identified specific haplotype in AGER and that a subpopulation of schizophrenic patients are more vulnerable to carbonyl stress.
KW - Advanced glycation end-products (AGEs)
KW - Carbonyl stress
KW - Endogenous secretory RAGE (esRAGE)
KW - Receptor for AGEs (RAGE)
KW - Schizophrenia
KW - Soluble RAGE (sRAGE)
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U2 - 10.1016/j.bbrc.2016.09.074
DO - 10.1016/j.bbrc.2016.09.074
M3 - Article
C2 - 27641663
AN - SCOPUS:84989848067
SN - 0006-291X
VL - 479
SP - 447
EP - 452
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -