Variants associated with Gaucher disease in multiple system atrophy

Jun Mitsui; Takashi Matsukawa; Hidenao Sasaki; Ichiro Yabe; Masaaki Matsushima; Alexandra Dürr; Alexis Brice; Hiroshi Takashima; Akio Kikuchi; Masashi Aoki; Hiroyuki Ishiura; Tsutomu Yasuda; Hidetoshi Date; Budrul Ahsan; Atsushi Iwata; Jun Goto; Yaeko Ichikawa; Yasuo Nakahara; Yoshio Momose; Yuji Takahashi; Kenju Hara; Akiyoshi Kakita; Mitsunori Yamada; Hitoshi Takahashi; Osamu Onodera; Masatoyo Nishizawa; Hirohisa Watanabe; Mizuki Ito; Gen Sobue; Kinya Ishikawa; Hidehiro Mizusawa; Kazuaki Kanai; Takamichi Hattori; Satoshi Kuwabara; Kimihito Arai; Shigeru Koyano; Yoshiyuki Kuroiwa; Kazuko Hasegawa; Tatsuhiko Yuasa; Kenichi Yasui; Kenji Nakashima; Hijiri Ito; Yuishin Izumi; Ryuji Kaji; Takeo Kato; Susumu Kusunoki; Yasushi Osaki; Masahiro Horiuchi; Tomoyoshi Kondo; Shigeo Murayama; Nobutaka Hattori; Mitsutoshi Yamamoto; Miho Murata; Wataru Satake; Tatsushi Toda; Alessandro Filla; Thomas Klockgether; Ullrich Wüllner; Garth Nicholson; Sid Gilman; Caroline M. Tanner; Walter A. Kukull; Mathew B. Stern; Virginia M.Y. Lee; John Q. Trojanowski; Eliezer Masliah; Phillip A. Low; Paola Sandroni; Laurie J. Ozelius; Tatiana Foroud; Shoji Tsuji

doi:10.1002/ACN3.185

Variants associated with Gaucher disease in multiple system atrophy

Jun Mitsui, Takashi Matsukawa, Hidenao Sasaki, Ichiro Yabe, Masaaki Matsushima, Alexandra Dürr, Alexis Brice, Hiroshi Takashima, Akio Kikuchi, Masashi Aoki, Hiroyuki Ishiura, Tsutomu Yasuda, Hidetoshi Date, Budrul Ahsan, Atsushi Iwata, Jun Goto, Yaeko Ichikawa, Yasuo Nakahara, Yoshio Momose, Yuji TakahashiKenju Hara, Akiyoshi Kakita, Mitsunori Yamada, Hitoshi Takahashi, Osamu Onodera, Masatoyo Nishizawa, Hirohisa Watanabe, Mizuki Ito, Gen Sobue, Kinya Ishikawa, Hidehiro Mizusawa, Kazuaki Kanai, Takamichi Hattori, Satoshi Kuwabara, Kimihito Arai, Shigeru Koyano, Yoshiyuki Kuroiwa, Kazuko Hasegawa, Tatsuhiko Yuasa, Kenichi Yasui, Kenji Nakashima, Hijiri Ito, Yuishin Izumi, Ryuji Kaji, Takeo Kato, Susumu Kusunoki, Yasushi Osaki, Masahiro Horiuchi, Tomoyoshi Kondo, Shigeo Murayama, Nobutaka Hattori, Mitsutoshi Yamamoto, Miho Murata, Wataru Satake, Tatsushi Toda, Alessandro Filla, Thomas Klockgether, Ullrich Wüllner, Garth Nicholson, Sid Gilman, Caroline M. Tanner, Walter A. Kukull, Mathew B. Stern, Virginia M.Y. Lee, John Q. Trojanowski, Eliezer Masliah, Phillip A. Low, Paola Sandroni, Laurie J. Ozelius, Tatiana Foroud, Shoji Tsuji

Neurology

Research output: Contribution to journal › Article › peer-review

Abstract

Objective: Glucocerebrosidase gene (GBA) variants that cause Gaucher disease are associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). To investigate the role of GBA variants in multiple system atrophy (MSA), we analyzed GBA variants in a large case-control series. Methods: We sequenced coding regions and flanking splice sites of GBA in 969 MSA patients (574 Japanese, 223 European, and 172 North American) and 1509 control subjects (900 Japanese, 315 European, and 294 North American). We focused solely on Gaucher-disease-causing GBA variants. Results: In the Japanese series, we found nine carriers among the MSA patients (1.65%) and eight carriers among the control subjects (0.89%). In the European series, we found three carriers among the MSA patients (1.35%) and two carriers among the control subjects (0.63%). In the North American series, we found five carriers among the MSA patients (2.91%) and one carrier among the control subjects (0.34%). Subjecting each series to a Mantel-Haenszel analysis yielded a pooled odds ratio (OR) of 2.44 (95% confidence interval [CI], 1.14-5.21) and a P-value of 0.029 without evidence of significant heterogeneity. Logistic regression analysis yielded similar results, with an adjusted OR of 2.43 (95% CI 1.15-5.37) and a P-value of 0.022. Subtype analysis showed that Gaucher-disease-causing GBA variants are significantly associated with MSA cerebellar subtype (MSA-C) patients (P = 7.3 9 10^-3). Interpretation: The findings indicate that, as in PD and DLB, Gaucher-disease-causing GBA variants are associated with MSA.

Original language	English (US)
Pages (from-to)	417-426
Number of pages	10
Journal	Annals of Clinical and Translational Neurology
Volume	2
Issue number	4
DOIs	https://doi.org/10.1002/ACN3.185
State	Published - Apr 2015

ASJC Scopus subject areas

General Neuroscience
Clinical Neurology

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10.1002/ACN3.185

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Mitsui, J., Matsukawa, T., Sasaki, H., Yabe, I., Matsushima, M., Dürr, A., Brice, A., Takashima, H., Kikuchi, A., Aoki, M., Ishiura, H., Yasuda, T., Date, H., Ahsan, B., Iwata, A., Goto, J., Ichikawa, Y., Nakahara, Y., Momose, Y., ... Tsuji, S. (2015). Variants associated with Gaucher disease in multiple system atrophy. Annals of Clinical and Translational Neurology, 2(4), 417-426. https://doi.org/10.1002/ACN3.185

Mitsui, J, Matsukawa, T, Sasaki, H, Yabe, I, Matsushima, M, Dürr, A, Brice, A, Takashima, H, Kikuchi, A, Aoki, M, Ishiura, H, Yasuda, T, Date, H, Ahsan, B, Iwata, A, Goto, J, Ichikawa, Y, Nakahara, Y, Momose, Y, Takahashi, Y, Hara, K, Kakita, A, Yamada, M, Takahashi, H, Onodera, O, Nishizawa, M, Watanabe, H, Ito, M, Sobue, G, Ishikawa, K, Mizusawa, H, Kanai, K, Hattori, T, Kuwabara, S, Arai, K, Koyano, S, Kuroiwa, Y, Hasegawa, K, Yuasa, T, Yasui, K, Nakashima, K, Ito, H, Izumi, Y, Kaji, R, Kato, T, Kusunoki, S, Osaki, Y, Horiuchi, M, Kondo, T, Murayama, S, Hattori, N, Yamamoto, M, Murata, M, Satake, W, Toda, T, Filla, A, Klockgether, T, Wüllner, U, Nicholson, G, Gilman, S, Tanner, CM, Kukull, WA, Stern, MB, Lee, VMY, Trojanowski, JQ, Masliah, E, Low, PA, Sandroni, P, Ozelius, LJ, Foroud, T & Tsuji, S 2015, 'Variants associated with Gaucher disease in multiple system atrophy', Annals of Clinical and Translational Neurology, vol. 2, no. 4, pp. 417-426. https://doi.org/10.1002/ACN3.185

@article{9f9527aa50f545548229eed363339ef4,

title = "Variants associated with Gaucher disease in multiple system atrophy",

abstract = "Objective: Glucocerebrosidase gene (GBA) variants that cause Gaucher disease are associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). To investigate the role of GBA variants in multiple system atrophy (MSA), we analyzed GBA variants in a large case-control series. Methods: We sequenced coding regions and flanking splice sites of GBA in 969 MSA patients (574 Japanese, 223 European, and 172 North American) and 1509 control subjects (900 Japanese, 315 European, and 294 North American). We focused solely on Gaucher-disease-causing GBA variants. Results: In the Japanese series, we found nine carriers among the MSA patients (1.65%) and eight carriers among the control subjects (0.89%). In the European series, we found three carriers among the MSA patients (1.35%) and two carriers among the control subjects (0.63%). In the North American series, we found five carriers among the MSA patients (2.91%) and one carrier among the control subjects (0.34%). Subjecting each series to a Mantel-Haenszel analysis yielded a pooled odds ratio (OR) of 2.44 (95% confidence interval [CI], 1.14-5.21) and a P-value of 0.029 without evidence of significant heterogeneity. Logistic regression analysis yielded similar results, with an adjusted OR of 2.43 (95% CI 1.15-5.37) and a P-value of 0.022. Subtype analysis showed that Gaucher-disease-causing GBA variants are significantly associated with MSA cerebellar subtype (MSA-C) patients (P = 7.3 9 10-3). Interpretation: The findings indicate that, as in PD and DLB, Gaucher-disease-causing GBA variants are associated with MSA.",

author = "Jun Mitsui and Takashi Matsukawa and Hidenao Sasaki and Ichiro Yabe and Masaaki Matsushima and Alexandra D{\"u}rr and Alexis Brice and Hiroshi Takashima and Akio Kikuchi and Masashi Aoki and Hiroyuki Ishiura and Tsutomu Yasuda and Hidetoshi Date and Budrul Ahsan and Atsushi Iwata and Jun Goto and Yaeko Ichikawa and Yasuo Nakahara and Yoshio Momose and Yuji Takahashi and Kenju Hara and Akiyoshi Kakita and Mitsunori Yamada and Hitoshi Takahashi and Osamu Onodera and Masatoyo Nishizawa and Hirohisa Watanabe and Mizuki Ito and Gen Sobue and Kinya Ishikawa and Hidehiro Mizusawa and Kazuaki Kanai and Takamichi Hattori and Satoshi Kuwabara and Kimihito Arai and Shigeru Koyano and Yoshiyuki Kuroiwa and Kazuko Hasegawa and Tatsuhiko Yuasa and Kenichi Yasui and Kenji Nakashima and Hijiri Ito and Yuishin Izumi and Ryuji Kaji and Takeo Kato and Susumu Kusunoki and Yasushi Osaki and Masahiro Horiuchi and Tomoyoshi Kondo and Shigeo Murayama and Nobutaka Hattori and Mitsutoshi Yamamoto and Miho Murata and Wataru Satake and Tatsushi Toda and Alessandro Filla and Thomas Klockgether and Ullrich W{\"u}llner and Garth Nicholson and Sid Gilman and Tanner, {Caroline M.} and Kukull, {Walter A.} and Stern, {Mathew B.} and Lee, {Virginia M.Y.} and Trojanowski, {John Q.} and Eliezer Masliah and Low, {Phillip A.} and Paola Sandroni and Ozelius, {Laurie J.} and Tatiana Foroud and Shoji Tsuji",

note = "Publisher Copyright: {\textcopyright} 2015 The Authors.",

year = "2015",

month = apr,

doi = "10.1002/ACN3.185",

language = "English (US)",

volume = "2",

pages = "417--426",

journal = "Annals of Clinical and Translational Neurology",

issn = "2328-9503",

publisher = "John Wiley and Sons Inc.",

number = "4",

}

TY - JOUR

T1 - Variants associated with Gaucher disease in multiple system atrophy

AU - Mitsui, Jun

AU - Matsukawa, Takashi

AU - Sasaki, Hidenao

AU - Yabe, Ichiro

AU - Matsushima, Masaaki

AU - Dürr, Alexandra

AU - Brice, Alexis

AU - Takashima, Hiroshi

AU - Kikuchi, Akio

AU - Aoki, Masashi

AU - Ishiura, Hiroyuki

AU - Yasuda, Tsutomu

AU - Date, Hidetoshi

AU - Ahsan, Budrul

AU - Iwata, Atsushi

AU - Goto, Jun

AU - Ichikawa, Yaeko

AU - Nakahara, Yasuo

AU - Momose, Yoshio

AU - Takahashi, Yuji

AU - Hara, Kenju

AU - Kakita, Akiyoshi

AU - Yamada, Mitsunori

AU - Takahashi, Hitoshi

AU - Onodera, Osamu

AU - Nishizawa, Masatoyo

AU - Watanabe, Hirohisa

AU - Ito, Mizuki

AU - Sobue, Gen

AU - Ishikawa, Kinya

AU - Mizusawa, Hidehiro

AU - Kanai, Kazuaki

AU - Hattori, Takamichi

AU - Kuwabara, Satoshi

AU - Arai, Kimihito

AU - Koyano, Shigeru

AU - Kuroiwa, Yoshiyuki

AU - Hasegawa, Kazuko

AU - Yuasa, Tatsuhiko

AU - Yasui, Kenichi

AU - Nakashima, Kenji

AU - Ito, Hijiri

AU - Izumi, Yuishin

AU - Kaji, Ryuji

AU - Kato, Takeo

AU - Kusunoki, Susumu

AU - Osaki, Yasushi

AU - Horiuchi, Masahiro

AU - Kondo, Tomoyoshi

AU - Murayama, Shigeo

AU - Hattori, Nobutaka

AU - Yamamoto, Mitsutoshi

AU - Murata, Miho

AU - Satake, Wataru

AU - Toda, Tatsushi

AU - Filla, Alessandro

AU - Klockgether, Thomas

AU - Wüllner, Ullrich

AU - Nicholson, Garth

AU - Gilman, Sid

AU - Tanner, Caroline M.

AU - Kukull, Walter A.

AU - Stern, Mathew B.

AU - Lee, Virginia M.Y.

AU - Trojanowski, John Q.

AU - Masliah, Eliezer

AU - Low, Phillip A.

AU - Sandroni, Paola

AU - Ozelius, Laurie J.

AU - Foroud, Tatiana

AU - Tsuji, Shoji

PY - 2015/4

Y1 - 2015/4

N2 - Objective: Glucocerebrosidase gene (GBA) variants that cause Gaucher disease are associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). To investigate the role of GBA variants in multiple system atrophy (MSA), we analyzed GBA variants in a large case-control series. Methods: We sequenced coding regions and flanking splice sites of GBA in 969 MSA patients (574 Japanese, 223 European, and 172 North American) and 1509 control subjects (900 Japanese, 315 European, and 294 North American). We focused solely on Gaucher-disease-causing GBA variants. Results: In the Japanese series, we found nine carriers among the MSA patients (1.65%) and eight carriers among the control subjects (0.89%). In the European series, we found three carriers among the MSA patients (1.35%) and two carriers among the control subjects (0.63%). In the North American series, we found five carriers among the MSA patients (2.91%) and one carrier among the control subjects (0.34%). Subjecting each series to a Mantel-Haenszel analysis yielded a pooled odds ratio (OR) of 2.44 (95% confidence interval [CI], 1.14-5.21) and a P-value of 0.029 without evidence of significant heterogeneity. Logistic regression analysis yielded similar results, with an adjusted OR of 2.43 (95% CI 1.15-5.37) and a P-value of 0.022. Subtype analysis showed that Gaucher-disease-causing GBA variants are significantly associated with MSA cerebellar subtype (MSA-C) patients (P = 7.3 9 10-3). Interpretation: The findings indicate that, as in PD and DLB, Gaucher-disease-causing GBA variants are associated with MSA.

AB - Objective: Glucocerebrosidase gene (GBA) variants that cause Gaucher disease are associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). To investigate the role of GBA variants in multiple system atrophy (MSA), we analyzed GBA variants in a large case-control series. Methods: We sequenced coding regions and flanking splice sites of GBA in 969 MSA patients (574 Japanese, 223 European, and 172 North American) and 1509 control subjects (900 Japanese, 315 European, and 294 North American). We focused solely on Gaucher-disease-causing GBA variants. Results: In the Japanese series, we found nine carriers among the MSA patients (1.65%) and eight carriers among the control subjects (0.89%). In the European series, we found three carriers among the MSA patients (1.35%) and two carriers among the control subjects (0.63%). In the North American series, we found five carriers among the MSA patients (2.91%) and one carrier among the control subjects (0.34%). Subjecting each series to a Mantel-Haenszel analysis yielded a pooled odds ratio (OR) of 2.44 (95% confidence interval [CI], 1.14-5.21) and a P-value of 0.029 without evidence of significant heterogeneity. Logistic regression analysis yielded similar results, with an adjusted OR of 2.43 (95% CI 1.15-5.37) and a P-value of 0.022. Subtype analysis showed that Gaucher-disease-causing GBA variants are significantly associated with MSA cerebellar subtype (MSA-C) patients (P = 7.3 9 10-3). Interpretation: The findings indicate that, as in PD and DLB, Gaucher-disease-causing GBA variants are associated with MSA.

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U2 - 10.1002/ACN3.185

DO - 10.1002/ACN3.185

M3 - Article

AN - SCOPUS:84945189692

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JO - Annals of Clinical and Translational Neurology

JF - Annals of Clinical and Translational Neurology

IS - 4

ER -

Variants associated with Gaucher disease in multiple system atrophy

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