Association between gene polymorphisms of SLC22A3 and methamphetamine use disorder.
BACKGROUND
Methamphetamine (MAP) is one of the most frequently used illegal substances in Japan, and family and twin studies have suggested that genetic factors contribute to psychostimulant dependence, including MAP dependence. Organic cation transporter 3 (OCT3) has been reported to be involved in the disposition of MAP as well as MAP-induced behavioral changes in animals. Moreover, SLC22A3 (which encodes OCT3) is a candidate gene for MAP dependence because it is located within a chromosomal region associated with substance dependence.


METHODS
Using 96 healthy control subjects, linkage disequilibrium (LD) within the SLC22A3 was investigated, and 5 single-nucleotide polymorphisms (SNPs) were selected as haplotype tag SNPs to search for an association with MAP dependence. Single-marker analyses and haplotype analyses of these SNPs were performed in 213 subjects with MAP dependence and 443 healthy controls.


RESULTS
SLC22A3 polymorphisms were not significantly associated with MAP dependence in any of the single-marker and haplotype analyses. When subjects with MAP dependence were divided into polysubstance and single-MAP users, genotype and allele frequency of SNP2 (p=0.024, p=0.011, respectively), allele frequency of SNP3 (p=0.037), and haplotypic frequencies for these 2 SNPs (p=0.0438) differed significantly between groups.


CONCLUSIONS
These results suggest that polymorphisms of SLC22A3 are related to the development of polysubstance use in Japanese patients with MAP dependence.
Aoyama
Nagisa
N
Department of Medical Technology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Takahashi
Nagahide
N
Kitaichi
Kiyoyuki
K
Ishihara
Ryoko
R
Saito
Shinichi
S
Maeno
Nobuhisa
N
Ji
Xiaofei
X
Takagi
Kenji
K
Sekine
Yoshimoto
Y
Iyo
Masaomi
M
Harano
Mutsuo
M
Komiyama
Tokutaro
T
Yamada
Mitsuhiko
M
Sora
Ichiro
I
Ujike
Hiroshi
H
Iwata
Nakao
N
Inada
Toshiya
T
Ozaki
Norio
N
D000328:Adult; D000483:Alleles; D019969:Amphetamine-Related Disorders / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D000697:Central Nervous System Stimulants / Q000009:adverse effects* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects* / Q000378:metabolism; D008875:Middle Aged; D027701:Organic Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000099254:Organic Cation Transporter 3
D000697:Central Nervous System Stimulants; D005819:Genetic Markers; D008694:Methamphetamine; D027701:Organic Cation Transport Proteins; D000099254:Organic Cation Transporter 3