Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor

Elan D. Louis; Wendy Jiang; Kathryn M. Pellegrino; Eileen Rios; Pam Factor-Litvak; Claire Henchcliffe; Wei Zheng

Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor
Louis, Elan D.
Jiang, Wendy
Pellegrino, Kathryn M.
Rios, Eileen
Factor-Litvak, Pam
Henchcliffe, Claire
Zheng, Wei
Center for Parkinson's Disease and Other Movement Disorders
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Essential tremor (ET) is a widespread late-life neurological disease. Genetic and environmental factors likely play an etiological role. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing neurotoxin. In 2002, we demonstrated elevated blood harmane concentrations in an initial sample of 100 ET cases compared to 100 controls. Between 2002 and 2007, we assembled a new and larger sample of ET cases and controls. We now attempt to replicate our previous findings. Cases and controls were frequency-matched on age, gender, and race. Blood harmane concentrations were quantified by high-performance liquid chromatography. Subjects comprised 150 ET cases and 135 controls (mean age 65.3 ± 15.5 vs. 65.5 ± 14.2 years, p = 0.94). Mean log blood harmane concentration was ∼50% higher in cases than controls (0.50 ± 0.54 g−10/ml vs. 0.35 ± 0.62 g−10/ml, p = 0.038). In a logistic regression analysis, log blood harmane concentration was associated with ET (ORadjusted 1.56, 95% CI 1.01–2.42, p = 0.04), and odds of ET was 1.90 (95% CI 1.07–3.39, p = 0.029) in the highest versus lowest log blood harmane tertile. Log blood harmane was highest in ET cases with familial ET (0.53 ± 0.57 g−10/ml), intermediate in cases with sporadic ET (0.43 ± 0.45 g−10/ml) and lowest in controls (0.35 ± 0.62 g−10/ml) (test for trend, p = 0.026). Blood harmane appears to be elevated in ET. The higher concentrations in familial ET suggests that the mechanism may involve genetic factors.
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Elan D. Louis, Wendy Jiang, Kathryn M. Pellegrino, Eileen Rios, Pam Factor-Litvak, Claire Henchcliffe, Wei Zheng, 2008, Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor, Columbia University Academic Commons, http://hdl.handle.net/10022/AC:P:9924.

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