Clin Psychopharmacol Neurosci.  2014 Apr;12(1):54-64.

A Pilot Study for Discovering Candidate Genes of Chromosome 18q21 in Methamphetamine Abusers: Case-control Association Study

• Lee BD
• Park JM
• Lee YM
• Moon ES
• Jeong HJ
• Chung YI
• Rim HD

Abstract

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.
CONCLUSION
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.

Keyword

Substance-related disorders; Methamphetamine; Psychotic disorders; Malic enzyme 2; Mapk4; Comorbidity

MeSH Terms

Case-Control Studies*
Comorbidity
DNA
Female
Genotype
Humans
Logistic Models
Male
Methamphetamine*
Neurons
Pilot Projects*
Polymorphism, Single Nucleotide
Protein Kinases
Psychotic Disorders
Data Accuracy
Substance-Related Disorders
DNA
Methamphetamine
Protein Kinases