A Pilot Study for Discovering Candidate Genes of Chromosome 18q21 in Methamphetamine Abusers: Case-control Association Study.
OBJECTIVE
It was previously suggested that the malic enzyme 2 (ME2) as the candidate gene for psychosis in fine mapping of chromosome 18q21. Chromosome 18q21 is also one of the possible regions that can contribute to addiction.


METHODS
We performed a pilot study for discovering candidate gene of chromosome 18q21 in the methamphetamine abusers for elucidating the candidate gene for methamphetamine addiction leading to psychosis. We have selected 30 unrelated controls (16 males, 14 females; age=59.8±10.4) and 37 male methamphetamine abusers (age=43.3±7.8). We analyzed 20 single nucleotide polymorphisms (SNPs) of 7 neuronal genes in chromosome 18q21 for DNA samples that was checked for the data quality and genotype error. The association between the case-control status and each individual SNP was measured using multiple logistic regression models (adjusting for age and sex as covariates). And we controlled false discovery rate (FDR) to deal with multiple testing problem.


RESULTS
We found 3 significant SNPs of 2 genes in chromosome 18q21 (p-value<0.05; adjusting for age as covariate) in methamphetamine abusers compared to controls. We also found 2 significant SNPs of 1 gene (p-value<0.05; adjusting for age and sex as covariates) (rs3794899, rs3794901:MAPK4). Two SNPs in MAPK4 gene were significant in both statistical groups.


CONCLUSIONS
MAPK4, the gene for mitogen-activated protein kinase 4, is one of the final 6 candidate genes including ME2 in 18q12-21 in our previous finemapping for psychosis. Our results suggest that MAPK4 can be a candidate gene that contribute to the methamphetamine addiction leading to psychosis.
Department of Psychiatry, Medical Research Institute, Pusan National University Hospital, Busan, Korea. ; Department of Psychiatry, Pusan National University College of Medicine, Yangsan, Korea.
Byung Dae
BD
Lee
Department of Psychiatry, Medical Research Institute, Pusan National University Hospital, Busan, Korea. ; Department of Psychiatry, Pusan National University College of Medicine, Yangsan, Korea.
Je Min
JM
Park
Department of Psychiatry, Medical Research Institute, Pusan National University Hospital, Busan, Korea. ; Department of Psychiatry, Pusan National University College of Medicine, Yangsan, Korea.
Young Min
YM
Lee
Department of Psychiatry, Medical Research Institute, Pusan National University Hospital, Busan, Korea. ; Department of Psychiatry, Pusan National University College of Medicine, Yangsan, Korea.
Eun Soo
ES
Moon
Department of Psychiatry, Medical Research Institute, Pusan National University Hospital, Busan, Korea. ; Department of Psychiatry, Pusan National University College of Medicine, Yangsan, Korea.
Hee Jeong
HJ
Jeong
Department of Psychiatry, Medical Research Institute, Pusan National University Hospital, Busan, Korea. ; Department of Psychiatry, Pusan National University College of Medicine, Yangsan, Korea.
Young In
YI
Chung
Department of Psychiatry, Kyungpook National University Hospital, Daegu, Korea.
Hyo Deog
HD
Rim
Comorbidity; Malic enzyme 2; Mapk4; Methamphetamine; Psychotic disorders; Substance-related disorders