Variants associated with Gaucher disease in multiple system atrophy. (28th February 2015)

• Record Type: Journal Article
• Authors: Mitsui, Jun; Matsukawa, Takashi; Sasaki, Hidenao; Yabe, Ichiro; Matsushima, Masaaki; Dürr, Alexandra; Brice, Alexis; Takashima, Hiroshi; Kikuchi, Akio; Aoki, Masashi; Ishiura, Hiroyuki; Yasuda, Tsutomu; Date, Hidetoshi; Ahsan, Budrul; Iwata, Atsushi; Goto, Jun; Ichikawa, Yaeko; Nakahara, Yasuo; Momose, Yoshio; Takahashi, Yuji; Hara, Kenju; Kakita, Akiyoshi; Yamada, Mitsunori; Takahashi, Hitoshi; Onodera, Osamu; Nishizawa, Masatoyo; Watanabe, Hirohisa; Ito, Mizuki; Sobue, Gen; Ishikawa, Kinya; Mizusawa, Hidehiro; Kanai, Kazuaki; Hattori, Takamichi; Kuwabara, Satoshi; Arai, Kimihito; Koyano, Shigeru; Kuroiwa, Yoshiyuki; Hasegawa, Kazuko; Yuasa, Tatsuhiko; Yasui, Kenichi; Nakashima, Kenji; Ito, Hijiri; Izumi, Yuishin; Kaji, Ryuji; Kato, Takeo; Kusunoki, Susumu; Osaki, Yasushi; Horiuchi, Masahiro; Kondo, Tomoyoshi; Murayama, Shigeo; Hattori, Nobutaka; Yamamoto, Mitsutoshi; Murata, Miho; Satake, Wataru; Toda, Tatsushi; Filla, Alessandro; Klockgether, Thomas; Wüllner, Ullrich; Nicholson, Garth; Gilman, Sid; Tanner, Caroline M.; Kukull, Walter A.; Stern, Mathew B.; Lee, Virginia M.‐Y.; Trojanowski, John Q.; Masliah, Eliezer; Low, Phillip A.; Sandroni, Paola; Ozelius, Laurie J.; Foroud, Tatiana; Tsuji, Shoji;
• Is Part Of: Annals of clinical and translational neurology. Volume 2:Number 4(2015:Apr.)
• Page Start: 417
• Page End: 426
• Publication Date: 2015-02-28
• Subjects: Nervous system -- Diseases -- Periodicals; Neurology -- Periodicals; 616.8005
• DOI: 10.1002/acn3.185
• Languages: English
• ISSNs: 2328-9503

Abstract

<abstract abstract-type="main" id="acn3185-abs-0001"> <title>Abstract</title> <sec id="acn3185-sec-0001" sec-type="section"> <title>Objective</title> <p>Glucocerebrosidase gene (<italic>GBA</italic>) variants that cause Gaucher disease are associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). To investigate the role of <italic>GBA</italic> variants in multiple system atrophy (MSA), we analyzed <italic>GBA</italic> variants in a large case–control series.</p> </sec> <sec id="acn3185-sec-0002" sec-type="section"> <title>Methods</title> <p>We sequenced coding regions and flanking splice sites of <italic>GBA</italic> 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 <italic>GBA</italic> variants.</p> </sec> <sec id="acn3185-sec-0003" sec-type="section"> <title>Results</title> <p>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 <italic>P</italic>‐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 <italic>P</italic>‐value of 0.022. Subtype analysis showed that Gaucher‐disease‐causing <italic>GBA</italic> variants are significantly associated with MSA cerebellar subtype (MSA‐C) patients (<italic>P </italic>=<italic> </italic>7.3 × 10<sup>−3</sup>).</p> </sec> <sec id="acn3185-sec-0004" sec-type="section"> <title>Interpretation</title> <p>The findings indicate that, as in PD and DLB, Gaucher‐disease‐causing <italic>GBA</italic> variants are associated with MSA.</p> </sec> </abstract>