Positive associations of polymorphisms in the metabotropic glutamate receptor type 8 gene (GRM8) with schizophrenia
Positive associations of polymorphisms in the metabotropic glutamate receptor type 8 gene (GRM8) with schizophrenia
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DOI：
10.1002/ajmg.b.20108
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发表时间：
2004-07-01
影响因子：
2.8
通讯作者：
Fukumaki, Y
中科院分区：
文献类型：
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作者：
Takaki, H;Kikuta, R;Fukumaki, Y
谷氨酸能功能障碍与精神分裂症的病理生理学密切相关。第三类代谢性谷氨酸受体4(MGluR4)、6、7和8被认为通过抑制突触处的谷氨酸释放来调节大脑中的谷氨酸能传递。我们用22个单核苷酸多态(SNPs)在100个病例对照配对中检测了GRM8区平均40.3kb的间隔，以检验精神分裂症与GRM8的关联。虽然我们观察到两个SNPs与精神分裂症显著相关，SNP18(rs2237748，等位基因：P=0.0279；基因：P=0.0124)和SNP19(rs2299472，等位基因：P=0.0302；基因：P=0.0127)，但经Bonferroni校正后，这两个SNPs均未显示与疾病显著相关。SNP18和SNP19均位于GRM8基因3‘端SNPs处于连锁不平衡(LD)的大区域(>；330kb)。我们还测试了精神分裂症的单倍型与构建的LD中SNPs的单倍型之间的关联。SNP5-SNP6(chi(2)=18.12，df=3，P=0.0004，P corr=0.0924，经Bonferroni校正后)、SNP4-SNP5-SNP6(chi(2)=27.50，df=7，P=0.0075，P=0.015，经Bonferroni校正后)和SNP5-SNP6-SNP7(chi(2)=23.92df=7，P=0.0011，Pcorr=0.0022，经Bonferroni校正后)具有显著相关性。因此，我们得出结论，在日本人中，至少有一个精神分裂症易感基因位于GRM8区域。(C)2003年Wiley-Liss，Inc.
The glutamatergic dysfunction has been implicated in pathophysiology of schizophrenia. The Group III metabotropic glutamate receptor 4 (mGluR4), 6, 7, and 8 are thought to modulate glutamatergic transmission in the brain by inhibiting glutamate release at the synapse. We tested association of schizophrenia with GRM8 using 22 single nucleotide polymorphisms (SNPs) with the average intervals of 40.3 kb in the GRM8 region in 100 case-control pairs for the SNPs. Although we observed significant associations of schizophrenia with two SNPs, SNP18 (rs2237748, allele: P = 0.0279; genotype: P = 0.0124) and SNP19 (rs2299472, allele: P = 0.0302; genotype: P = 0.0127), none of two SNPs showed significant association with disease after Bonferroni correction. Both SNP18 and SNP19 were included in a large region (>330 kb) in which SNPs are in linkage disequilibrium (LD) at the 3' region of GRM8. We also tested haplotype association of schizophrenia with constructed haplotypes of the SNPs in LD. Significant associations were detected for the combinations of SNP5-SNP6 (chi(2) = 18.12, df = 3, P = 0.0004, P corr = 0.0924 with Bonferroni correction), SNP4-SNP5-SNP6 (chi(2) = 27.50, df = 7, P = 0.0075, P corr = 0.015 with Bonferroni correction), and SNP5-SNP6-SNP7 (chi(2) = 23.92, df = 7, P = 0.0011, P corr = 0.0022 with Bonferroni correction). Thus, we conclude that at least one susceptibility locus for schizophrenia is located within the GRM8 region in Japanese. (C) 2003 Wiley-Liss, Inc.