Association of ALS with head injury, cigarette smoking and APOE genotypes

Schmidt, Silke; Kwee, Lydia Coulter; Allen, Kelli D.; Oddone, Eugene Z.

doi:10.1016/j.jns.2010.01.011

« Previous Next »Journal of the Neurological Sciences
Volume 291, Issue 1 , Pages 22-29, 15 April 2010

Association of ALS with head injury, cigarette smoking and APOE genotypes

Silke Schmidt
- Center for Human Genetics, Duke University Medical Center, 595 Lasalle Street, Durham, North Carolina, 27710, USA
- Epidemiology Research and Information Center, Durham VAMC, 508 Fulton Street, Durham, North Carolina, 27705, USA
- Department of Medicine, Duke University Medical Center, 2301 Erwin Road, Durham, North Carolina, 27710, USA
- Corresponding author. Center for Human Genetics, Department of Medicine, Duke University Medical Center, Box 3445, Durham, NC 27710, United States. Tel.: +1 919 684 0624; fax: +1 919 684 0925.
- Present address: Institute for Medical Informatics and Statistics, Christian-Albrechts University, Kiel, Germany.
Lydia Coulter Kwee
- Center for Human Genetics, Duke University Medical Center, 595 Lasalle Street, Durham, North Carolina, 27710, USA
- Epidemiology Research and Information Center, Durham VAMC, 508 Fulton Street, Durham, North Carolina, 27705, USA
- Department of Medicine, Duke University Medical Center, 2301 Erwin Road, Durham, North Carolina, 27710, USA
Kelli D. Allen
- Epidemiology Research and Information Center, Durham VAMC, 508 Fulton Street, Durham, North Carolina, 27705, USA
- Department of Medicine, Duke University Medical Center, 2301 Erwin Road, Durham, North Carolina, 27710, USA
Eugene Z. Oddone
- Epidemiology Research and Information Center, Durham VAMC, 508 Fulton Street, Durham, North Carolina, 27705, USA
- Department of Medicine, Duke University Medical Center, 2301 Erwin Road, Durham, North Carolina, 27710, USA

Received 23 September 2009; received in revised form 7 January 2010; accepted 12 January 2010. published online 03 February 2010.

Abstract

Objective

An increased risk of ALS has been reported for US veterans, but the cause is unknown. Since head injury and cigarette smoking are two previously implicated environmental risk factors that are more common in military than civilian study populations, we tested their association with ALS in a US veteran study population.

Methods

We used logistic regression to examine the association of ALS with head injury and cigarette smoking in 241 incident cases and 597 controls. Since APOE is a plausible ALS candidate gene, we also tested its main effect and its statistical interaction with these environmental exposures.

Results

Cigarette smoking was not associated with ALS in this predominantly male and Caucasian population. Veterans who had experienced head injuries during the last 15years before the reference date had an adjusted odds ratio of 2.33 (95% confidence interval 1.18–4.61), relative to veterans without any head injuries. This association was strongest in APOE-4 carriers.

Conclusions

Our results add to the body of evidence suggesting that head injuries may be a risk factor for multiple neurodegenerative diseases, including ALS. We hypothesize that the strength of association between head injuries and ALS may depend upon APOE genotype.

Keywords: Case–control study, US veterans, Candidate gene, Gene–environment interaction, Neurodegeneration