Shibata Hiroki, Shibata Atsushi, Ninomiya Hideaki, Tashiro Nobutada, Fukumaki Yasuyuki
Division of Disease Genes, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Psychiatry Res. 2002 Dec 15;113(1-2):59-67. doi: 10.1016/s0165-1781(02)00231-7.
The glutamatergic dysfunction hypothesis of schizophrenia suggests genes involved in glutamatergic transmission as candidates for schizophrenia-susceptibility genes. The GluR6 kainate receptor gene GRIK2 is located on chromosome 6q16.3-q21, a schizophrenia susceptibility region, as suggested by multiple linkage studies. We examined 15 SNPs evenly distributed in the entire GRIK2 region (>700 kb) in Japanese patients with schizophrenia (n=100) and controls (n=100). Neither genotype nor allele frequency showed a significant association with the disorder. We constructed 2-SNP haplotypes from the 15 SNPs. Although we observed three long linkage disequilibrium blocks (>150 kb) within the GRIK2 region, none of the pairwise haplotypes showed a significant association with the disorder. Therefore, we conclude that GRIK2 does not play a major role in the pathogenesis of schizophrenia in the Japanese population.
精神分裂症的谷氨酸能功能障碍假说表明，参与谷氨酸能传递的基因是精神分裂症易感基因的候选者。多个连锁研究表明，谷氨酸受体6（GluR6）红藻氨酸受体基因GRIK2位于6号染色体6q16.3-q21区域，该区域是一个精神分裂症易感区域。我们在100例日本精神分裂症患者和100例对照中，检测了均匀分布于整个GRIK2区域（>700 kb）的15个单核苷酸多态性（SNP）。基因型和等位基因频率均未显示与该疾病有显著关联。我们从这15个SNP构建了双SNP单倍型。尽管我们在GRIK2区域内观察到3个长连锁不平衡块（>150 kb），但没有任何成对单倍型显示与该疾病有显著关联。因此，我们得出结论，在日本人群中，GRIK2在精神分裂症的发病机制中不发挥主要作用。
