Association study of polymorphisms in the neutral amino acid transporter genes SLC1A4, SLC1A5 and the glycine transporter genes SLC6A5, SLC6A9 with schizophrenia.
BACKGROUND
Based on the glutamatergic dysfunction hypothesis for schizophrenia pathogenesis, we have been performing systematic association studies of schizophrenia with the genes involved in glutametergic transmission. We report here association studies of schizophrenia with SLC1A4, SLC1A5 encoding neutral amino acid transporters ASCT1, ASCT2, and SLC6A5, SLC6A9 encoding glycine transporters GLYT2, GLYT1, respectively.


METHODS
We initially tested the association of 21 single nucleotide polymorphisms (SNPs) distributed in the four gene regions with schizophrenia using 100 Japanese cases-control pairs and examined allele, genotype and haplotype association with schizophrenia. The observed nominal significance were examined in the full-size samples (400 cases and 420 controls).


RESULTS
We observed nominally significant single-marker associations with schizophrenia in SNP2 (P = 0.021) and SNP3 (P = 0.029) of SLC1A4, SNP1 (P = 0.009) and SNP2 (P = 0.022) of SLC6A5. We also observed nominally significant haplotype associations with schizophrenia in the combinations of SNP2-SNP7 (P = 0.037) of SLC1A4 and SNP1-SNP4 (P = 0.043) of SLC6A5. We examined all of the nominal significance in the Full-size Sample Set, except one haplotype with insufficient LD. The significant association of SNP1 of SLC6A5 with schizophrenia was confirmed in the Full-size Sample Set (P = 0.018).


CONCLUSIONS
We concluded that at least one susceptibility locus for schizophrenia may be located within or nearby SLC6A5, whereas SLC1A4, SLC1A5 and SLC6A9 are unlikely to be major susceptibility genes for schizophrenia in the Japanese population.
Deng
Xiangdong
X
Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan. luckbird@gen.kyushu-u.ac.jp
Sagata
Noriaki
N
Takeuchi
Naoko
N
Tanaka
Masami
M
Ninomiya
Hideaki
H
Iwata
Nakao
N
Ozaki
Norio
N
Shibata
Hiroki
H
Fukumaki
Yasuyuki
Y
D000483:Alleles; D026962:Amino Acid Transport System ASC / Q000235:genetics*; D016022:Case-Control Studies; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D050487:Glycine Plasma Membrane Transport Proteins / Q000235:genetics*; D006239:Haplotypes; D006250:Hartnup Disease / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D011110:Polymorphism, Genetic / Q000235:genetics*; D012559:Schizophrenia / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*
D026962:Amino Acid Transport System ASC; D050487:Glycine Plasma Membrane Transport Proteins; D015778:Minor Histocompatibility Antigens; C498848:SLC1A4 protein, human; C420506:SLC1A5 protein, human; C493271:SLC6A5 protein, human; C493268:SLC6A9 protein, human