The nonsynonymous Thr105Ile polymorphism of the histamine N-methyltransferase is associated to the risk of developing essential tremor.
OBJECTIVE
We analyzed in patients with essential tremor (ET) the Thr105Ile polymorphism of the Histamine N-methyltransferase (HNMT) enzyme that is associated to Parkinson's disease (PD) risk.


METHODS
Leukocytary DNA from 204 ET patients and a control group of 295 unrelated healthy individuals was studied for the nonsynonymous HNMT Thr105Ile polymorphism by using amplification-restriction analyses.


RESULTS
Patients with ET showed a higher frequency of homozygous HNMT 105Thr genotypes leading to high metabolic activity (p < 0.015) with a statistically significant gene-dose effect, as compared to healthy subjects. These findings were independent of gender, and of tremor localization, but the association of the HNMT polymorphism is more prominent among patients with late-onset ET (p < 0.007).


CONCLUSIONS
These results, combined with previous findings indicating alterations in the frequency for the HNMT Thr105Ile polymorphism in patients with PD, suggest that alterations of histamine homeostasis in the SNC are associated with the risk of movement disorders.
Department of Pharmacology & Psychiatry, Medical School, University of Extremadura, Badajoz, Spain.
Maria C
MC
Ledesma
Elena
E
García-Martín
Hortensia
H
Alonso-Navarro
Carmen
C
Martínez
Félix Javier
FJ
Jiménez-Jiménez
Julián
J
Benito-León
Inmaculada
I
Puertas
Lluisa
L
Rubio
Tomás
T
López-Alburquerque
José A G
JA
Agúndez
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution / Q000235:genetics; D001923:Brain Chemistry / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D020329:Essential Tremor / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006637:Histamine N-Methyltransferase / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007532:Isoleucine / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D013912:Threonine / Q000235:genetics; D055815:Young Adult
D007532:Isoleucine; D013912:Threonine; D006637:Histamine N-Methyltransferase