No association between gluten sensitivity and amyotrophic lateral sclerosis.
To examine evidence for a role of gluten sensitivity (GS) or celiac disease (CD) in ALS etiology, we included participants from a population-based case-control study in The Netherlands between January 2006 and December 2015. We compared levels and seroprevalence of IgA antibodies to tissue transglutaminase 6 (TG6) in 359 ALS patients and 359 controls, and to transglutaminase 2 (TG2) and endomysium (EMA) in 199 ALS patients and 199 controls. Questionnaire data on 1829 ALS patients and 3920 controls were examined for CD or gluten-free diets (GFD). Genetic correlation and HLA allele frequencies were analyzed using two genome-wide association studies: one on ALS (12,577 cases, 23,475 controls), and one on CD (4533 cases, 10,750 controls). We found one patient with TG6, TG2 and EMA antibodies who had typical ALS and no symptoms of GS. TG6 antibody concentrations and positivity, CD prevalence and adherence to a GFD were similar in patients and controls (p > 0.66) and in these patients disease progression was compatible with typical ALS. CD and ALS were not found to be genetically correlated (p > 0.37). CD-associated HLA allele frequencies were similar in patients and controls (p > 0.28). In conclusion, we found no serological evidence for involvement of gluten-related antibodies in ALS etiology nor did we observe an association between CD and ALS in medical history or genetic data, indicating that there is no evidence in our data for an association between the two diseases. Hence, a role for a GFD in the ALS treatment seems unlikely.
Department of Neurology, Brain Center Rudolf Magnus, F02.230, University Medical Center Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands.
Anne E
AE
Visser
Department of Neurology, Brain Center Rudolf Magnus, F02.230, University Medical Center Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands.|Department of Epidemiology and Biostatistics, MRC-PHE Center for Environment and Health, School of Public Health, Imperial College London, London, UK.
Raha
R
Pazoki
Department of Neurology, Brain Center Rudolf Magnus, F02.230, University Medical Center Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands.
Sara L
SL
Pulit
Department of Neurology, Brain Center Rudolf Magnus, F02.230, University Medical Center Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands.
Wouter
W
van Rheenen
Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Joost
J
Raaphorst
Department of Neurology, Amsterdam Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Anneke J
AJ
van der Kooi
Genetics Department, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Isis
I
Ricaño-Ponce
Genetics Department, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Cisca
C
Wijmenga
Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Henny G
HG
Otten
Department of Neurology, Brain Center Rudolf Magnus, F02.230, University Medical Center Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands.
Jan H
JH
Veldink
Department of Neurology, Brain Center Rudolf Magnus, F02.230, University Medical Center Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands. L.H.vandenBerg@umcutrecht.nl.
Leonard H
LH
van den Berg
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D000906:Antibodies / Q000097:blood*; D016022:Case-Control Studies; D015331:Cohort Studies; D055050:Diet, Gluten-Free / Q000379:methods; D005260:Female; D005983:Glutens / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D012044:Regression Analysis; D011795:Surveys and Questionnaires; D011503:Transglutaminases / Q000276:immunology; D055815:Young Adult
D000906:Antibodies; D005983:Glutens; C532876:TGM6 protein, human; D011503:Transglutaminases
Amyotrophic lateral sclerosis; Epidemiology; Genome-wide association studies; Gluten; Serology