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No association between biopsy-verified celiac disease and subsequent amyotrophic lateral sclerosis--a population-based cohort study.

ABSTRACT: Earlier data suggest an association between amyotrophic lateral sclerosis (ALS) and autoimmune disease, but data on its association with celiac disease (CD) are limited.The risk of ALS in 29 093 individuals with CD, according to small intestine biopsy (villous atrophy, Marsh 3) carried out at Sweden's 28 pathology departments in 1969-2008, was compared with that in 144 515 age- and sex-matched reference individuals from the general population. ALS was defined as a hospitalization or outpatient visit with ALS according to the Swedish Patient Register. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for ALS.During follow-up 12 (3.7/100 000 person-years) individuals with CD and 56 (3.5/100 000 person-years) reference individuals had a diagnosis of ALS. This corresponded to an HR of 1.0 (95% CI 0.5-1.8). HRs were significantly higher in the first year of follow-up (4.1; 1.2-13.4) than 1-5 years after first CD diagnosis (0.8; 0.2-2.7) or after more than 5 years of follow-up (0.5; 0.2-1.5). Relative risk estimates were similar in men and women but were higher at the end of the study period [HR for ALS in patients diagnosed with CD in year 2000 or later was 2.1 (95% CI 0.9-4.8)].This study found no association between CD and ALS. Earlier reports of a positive association may be due to surveillance bias just after CD diagnosis or expedited diagnostic work-up of ALS.

SUBMITTER: Ludvigsson JF

PROVIDER: S-EPMC4057356 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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No association between biopsy-verified celiac disease and subsequent amyotrophic lateral sclerosis--a population-based cohort study.

Ludvigsson J F JF Mariosa D D Lebwohl B B Fang F F

European journal of neurology 20140407 7

<h4>Background and purpose</h4>Earlier data suggest an association between amyotrophic lateral sclerosis (ALS) and autoimmune disease, but data on its association with celiac disease (CD) are limited.<h4>Methods</h4>The risk of ALS in 29 093 individuals with CD, according to small intestine biopsy (villous atrophy, Marsh 3) carried out at Sweden's 28 pathology departments in 1969-2008, was compared with that in 144 515 age- and sex-matched reference individuals from the general population. ALS w ...[more]

PMID: 24708265

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Project description:ImportanceWhile systemic inflammation has been implicated in the aetiology of selected neurodegenerative disorders, its role in the development of amyotrophic lateral sclerosis (ALS) is untested.ObjectiveTo quantify the relationship of C-reactive protein (CRP), an acute-phase reactant and marker of systemic inflammation, with ALS occurrence.Design setting participantsUK Biobank, a prospective cohort study of 502,649 participants who were aged 37 to 73 years when examined at research centres between 2006 and 2010.ExposureVenous blood was collected at baseline in the full cohort and assayed for CRP. Repeat measurement was made 3-7 years later in a representative subgroup (N=14,514) enabling correction for regression dilution.Main outcomes and measuresALS as ascertained via national hospitalisation and mortality registries. We computed multi-variable hazard ratios with accompanying 95% confidence intervals for log-transformed CRP expressed as standard deviation and tertiles.ResultsIn an analytical sample of 400,884 individuals (218,203 women), a mean follow-up of 12 years gave rise to 231 hospitalisations and 223 deaths ascribed to ALS. After adjustment for covariates which included health behaviours, comorbidity, and socio-economic status, a one standard deviation higher log-CRP was associated with elevated rates of both ALS mortality (hazard ratios; 95% confidence intervals: 1.32; 1.13, 1.53) and hospitalisations (1.20; 1.00, 1.39). There was evidence of dose-response effects across tertiles of CRP for both outcomes (p for trend≤0.05). Correction for regression dilution led to a strengthening of the relationship with CRP for both mortality (1.62; 1.27, 2.08) and hospitalisations (1.37; 1.05, 1.76) ascribed to ALS.Conclusions and relevanceHigher levels of CRP, a blood-based biomarker widely captured in clinical practice, were associated with a higher subsequent risk of ALS.Key pointsQuestion: Is C-reactive protein (CRP), a marker of systemic inflammation widely used in clinical practice, associated with later risk of amyotrophic lateral sclerosis (ALS)?Findings: Following 11 years disease surveillance in 400,884 individuals (218,203 women), after adjustment for covariates and correction for regression dilution, a one standard deviation higher CRP levels were associations with both mortality (hazard ratio; 95% confidence interval: 1.62; 1.27, 2.08) and hospitalisations (1.37; 1.05, 1.76) ascribed to ALS.Meaning: In the present study, CRP has a dose-response relationship with the risk of later ALS.

Project description:ImportancePersistent environmental pollutants may represent a modifiable risk factor involved in the gene-time-environment hypothesis in amyotrophic lateral sclerosis (ALS).ObjectiveTo evaluate the association of occupational exposures and environmental toxins on the odds of developing ALS in Michigan.Design, setting, and participantsCase-control study conducted between 2011 and 2014 at a tertiary referral center for ALS. Cases were patients diagnosed as having definitive, probable, probable with laboratory support, or possible ALS by revised El Escorial criteria; controls were excluded if they were diagnosed as having ALS or another neurodegenerative condition or if they had a family history of ALS in a first- or second-degree blood relative. Participants completed a survey assessing occupational and residential exposures. Blood concentrations of 122 persistent environmental pollutants, including organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and brominated flame retardants (BFRs), were measured using gas chromatography-mass spectrometry. Multivariable models with self-reported occupational exposures in various exposure time windows and environmental toxin blood concentrations were separately fit by logistic regression models. Concordance between the survey data and pollutant measurements was assessed using the nonparametric Kendall τ correlation coefficient.Main outcomes and measuresOccupational and residential exposures to environmental toxins, and blood concentrations of 122 persistent environmental pollutants, including OCPs, PCBs, and BFRs.ResultsParticipants included 156 cases (mean [SD] age, 60.5 [11.1] years; 61.5% male) and 128 controls (mean [SD] age, 60.4 [9.4] years; 57.8% male); among them, 101 cases and 110 controls had complete demographic and pollutant data. Survey data revealed that reported pesticide exposure in the cumulative exposure windows was significantly associated with ALS (odds ratio [OR] = 5.09; 95% CI, 1.85-13.99; P = .002). Military service was also associated with ALS in 2 time windows (exposure ever happened in entire occupational history: OR = 2.31; 95% CI, 1.02-5.25; P = .046; exposure ever happened 10-30 years ago: OR = 2.18; 95% CI, 1.01-4.73; P = .049). A multivariable model of measured persistent environmental pollutants in the blood, representing cumulative occupational and residential exposure, showed increased odds of ALS for 2 OCPs (pentachlorobenzene: OR = 2.21; 95% CI, 1.06-4.60; P = .04; and cis-chlordane: OR = 5.74; 95% CI, 1.80-18.20; P = .005), 2 PCBs (PCB 175: OR = 1.81; 95% CI, 1.20-2.72; P = .005; and PCB 202: OR = 2.11; 95% CI, 1.36-3.27; P = .001), and 1 BFR (polybrominated diphenyl ether 47: OR = 2.69; 95% CI, 1.49-4.85; P = .001). There was modest concordance between survey data and the measurements of persistent environmental pollutants in blood; significant Kendall τ correlation coefficients ranged from -0.18 (Dacthal and "use pesticides to treat home or yard") to 0.24 (trans-nonachlor and "store lawn care products in garage").Conclusions and relevanceIn this study, persistent environmental pollutants measured in blood were significantly associated with ALS and may represent modifiable ALS disease risk factors.

Dataset Information

No association between biopsy-verified celiac disease and subsequent amyotrophic lateral sclerosis--a population-based cohort study.

Publications

No association between biopsy-verified celiac disease and subsequent amyotrophic lateral sclerosis--a population-based cohort study.

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