EXTENDED REPORT

The Met66 allele of the functional Val66Met polymorphism in the brain-derived neurotrophic factor gene confers protection against neurocognitive dysfunction in systemic lupus erythematosus

G Oroszi^1,*, L Lapteva^2,*, E Davis¹, C H Yarboro², T Weickert³, T Roebuck-Spencer⁴, J Bleiberg⁴, D Rosenstein³, M Pao³, P E Lipsky², D Goldman¹, R H Lipsky¹, G G Illei²

¹ Laboratory of Neurogenetics, National Institute of Alcohol Abuse and Alcoholism, NIH, Bethesda, Maryland, USA
² National Institute of Arthritis, Musculoskeletal and Skin Diseases, NIH
³ National Institute of Mental Health, NIH
⁴ National Rehabilitation Hospital, Washington, DC, USA

Correspondence to:
G G Illei
Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, 10 Center Drive, Room 1N114, Bethesda, MD 20892, USA;illeig{at}mail.nih.gov

Background: A common functional polymorphism of the brain-derived neurotrophic factor gene (BDNF Val66Met) was previously associated with diminished episodic memory performance in healthy people. As cognitive function is commonly impaired in patients with systemic lupus erythematosus (SLE), the association of the BDNF Val66Met with neurocognitive function was studied.

Objective: To study the association of the BDNF Val66Met with neurocognitive function in a cohort of patients with SLE.

Methods: Cognitive function was assessed in 59 patients with SLE with no previous or current central nervous system involvement. Cognitive tests were grouped into five domains (memory, attention/executive function, visuospatial skills, motor function and psychomotor speed) and used to obtain domain Z scores, reflecting the difference between averaged scores of performance on individual tests and published norms in each domain. Genotyping was carried out using a 5'-nuclease assay with 99.9% accuracy. Unpaired t test was used to assess the relationship between genotypes and cognitive function, whereas the effect of possible confounders was assessed in a multivariate analysis.

Results: Patients carrying the Met66 allele scored significantly higher on psychomotor, attention/executive and motor function tests, resulting in significantly higher domain Z scores for the psychomotor (p = 0.005) and motor (p = 0.002) domains.

Conclusions: The BDNF Met66 allele was associated with better cognitive functioning in the psychomotor and motor domains, even after controlling for differences in ethnicity, sex, depression status and prednisone treatment. These data suggest that the BDNF Met66 allele confers protection against the decline of motor and psychomotor cognitive functions in patients with longstanding SLE.

Abbreviations: BDNF, brain-derived neurotrophic factor; CNS, central nervous system; SLE, systemic lupus erythematosus

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