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

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Objective: It was previously suggested that the malic enzyme 2 (ME2 ) as the candidate gene for psychosis in finemappingof 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 abusersfor 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 nucleotidepolymorphisms (SNPs) of 7 neuronal genes in chromosome 18q21 for DNA samples that was checked for the data qualityand genotype error. The association between the case-control status and each individual SNP was measured using multiplelogistic regression models (adjusting for age and sex as covariates). And we controlled false discovery rate (FDR) to deal withmultiple testing problem. Results: We found 3 significant SNPs of 2 genes in chromosome 18q21 (p-value<0.05; adjusting for age as covariate) in methamphetamineabusers compared to controls. We also found 2 significant SNPs of 1 gene (p-value<0.05; adjusting for age andsex 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 in18q12-21 in our previous finemapping for psychosis. Our results suggest that MAPK4 can be a candidate gene that contributeto the methamphetamine addiction leading to psychosis.

Abstract

Objective: It was previously suggested that the malic enzyme 2 (ME2 ) as the candidate gene for psychosis in finemappingof 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 abusersfor 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 nucleotidepolymorphisms (SNPs) of 7 neuronal genes in chromosome 18q21 for DNA samples that was checked for the data qualityand genotype error. The association between the case-control status and each individual SNP was measured using multiplelogistic regression models (adjusting for age and sex as covariates). And we controlled false discovery rate (FDR) to deal withmultiple testing problem. Results: We found 3 significant SNPs of 2 genes in chromosome 18q21 (p-value<0.05; adjusting for age as covariate) in methamphetamineabusers compared to controls. We also found 2 significant SNPs of 1 gene (p-value<0.05; adjusting for age andsex 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 in18q12-21 in our previous finemapping for psychosis. Our results suggest that MAPK4 can be a candidate gene that contributeto the methamphetamine addiction leading to psychosis.

참고문헌 (70)

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