G-蛋白信号转导调节子4(RGS4)基因多态性与精神分裂症的关联研究

Association Study of the Regulator of G-protein Signaling 4 (RGS4) Polymorphisms with Schizophrenia

目的：探讨G-蛋白信号转导调节子4（regulator of G-protein signaling-4，RGS4）基因与精神分裂症及临床症状的遗传关联。方法：应用病例对照关联研究设计，采用聚合酶链式反应-限制性片断长度多态性（PCR-RFLP）和DNA测序方法，分析386例精神分裂症患者和390例正常对照者中RGS4基因4个单核苷酸多态性（SNP）位点与精神分裂症的关联。并采用阳性和阴性症状量表（PANSS）评估患者的临床症状，进一步分析PANSS因子分与RGS4多态性的关联。结果：RGS4基因的两个多态性位点rs12753561（T〉G，χ^2=8．970，P=0．002）和rs10759（C〉A，χ^2=13．773，F=0．002，P=0．002）与精神分裂症关联，由上述4个SNPs组成的多个单体型如AAGA（χ^2=11．120，P=0．0008，OR=0．52，95％CI=0．36—0．77）和GGGC（χ^2=10．096，P=0．001，OR=1．43，95％CI=1．15—1．79）均与精神分裂症关联。PANSS量表的阴性症状因子分与rs12753561（t=2．216，P=0．029）和rs10759（t=2．543，P=0．012）关联。结论：RGS4基因多态性与精神分裂症及阴性和一般精神病理症状显著关联。

Objective： To explore the association of the regulator of G - protein signaling 4 （ RGS4 ） polymorphisms with schizophrenia. Methods： Four single nucleotide polymorphisms （ SNPs ） of RGS4 gene were analyzed in a sample of 386 schizophrenic patients and 390 healthy controls, using the polymerase chain reaction - based restriction fragment length polymorphism （ PCR - RFLP） genotyping or DNA sequencing. Results： SNP rs12753561 （ T 〉 G, χ^2 =8. 970, P=0. 002） and rs10759 of RGS4 gene were significantly associated with schizophrenia （C 〉 A, χ^2 = 13. 773, P = 0. 002 ） . When constructed with two, three and four markers, a number of haplotypes were significantly associated with schizophrenia, such as AAGA （ χ^2 = 11. 120, P =0. 0008, OR =0. 52, 95% CI =0. 36 -0.77 ） and GGGC （ χ^2 = 10. 096, P =0. 001, OR = 1.43, 95% CI = 1.15 - 1.79） . When the subjects examined with the positive and negative syndrome scale （ PANSS ） , above two SNPs were associated with the negative syndrome （ P = 0. 029, 0. 012 ） . Conclusion： These results further contribute to the evidence that variations in the RGS4 gene have an effect on schizophrenia susceptibility.