Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis

Publication

Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis

Journal Paper/Review - Dec 1, 2011

van den Berg Leonard H, Heutink Peter, van Hilten Jacobus J, Verbaan Dagmar, de Visser Marianne, van der Kooi Anneke J, Weber Markus, Klein Christine, Waibel Stefan, Fernández-Santiago Rubén, Birve Anna, Dahlberg Caroline, Lemmens Robin, Hennekam Eric A M, Cuppen Edwin, van de Warrenburg Bart P, Landers John E, de Bakker Paul I W, Pasterkamp R Jeroen, Veldink Jan H, Ophoff Roel A, Robberecht Wim, Ludolph Albert C, Gasser Thomas, Silani Vincenzo, Brown Robert H, Berg Daniela, Van Damme Philip, Pezzoli Gianni, Keagle Pamela, LeClerc Ashley Lyn, Fumoto Katsumi, Diekstra Frank P, Koppers Max, Blauw Hylke M, Schulte Claudia, Groen Ewout J N, Andersen Peter M, Ticozzi Nicola, van Vught Paul W J, Schelhaas Helenius J, Bloem Bastiaan R, Scheffer Hans, Goldwurm Stefano, Mariani Claudio, Folkerth Rebecca D, Wu David, Kishikawa Hiroko, Yu Wenhao, Hu Guo-fu, Lowe Patrick P, Wills Anne-Marie, van Rheenen Wouter, van Blitterswijk Marka, van Nuenen Bart F L, van Es Michael A

Citation

van den Berg L, Heutink P, van Hilten J, Verbaan D, de Visser M, van der Kooi A, Weber M, Klein C, Waibel S, Fernández-Santiago R, Birve A, Dahlberg C, Lemmens R, Hennekam E, Cuppen E, van de Warrenburg B, Landers J, de Bakker P, Pasterkamp R, Veldink J, Ophoff R, Robberecht W, Ludolph A, Gasser T, Silani V, Brown R, Berg D, Van Damme P, Pezzoli G, Keagle P, LeClerc A, Fumoto K, Diekstra F, Koppers M, Blauw H, Schulte C, Groen E, Andersen P, Ticozzi N, van Vught P, Schelhaas H, Bloem B, Scheffer H, Goldwurm S, Mariani C, Folkerth R, Wu D, Kishikawa H, Yu W, Hu G, Lowe P, Wills A, van Rheenen W, van Blitterswijk M, van Nuenen B, van Es M. Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis. Ann Neurol 2011; 70:964-73.

Type

Journal Paper/Review (English)

Journal

Ann Neurol 2011; 70

Publication Date

Dec 1, 2011

Issn Electronic

1531-8249

Pages

964-73

Brief description/objective

OBJECTIVE
Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD.

METHODS
We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel-Haenszel procedure was used to estimate odds ratios.

RESULTS
Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10(-6) for ALS and p = 4.3 × 10(-5) for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD.

INTERPRETATION
The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD.