胱硫醚-β-合成酶基因多态性与精神分裂症核心家系的关联研究

Nuclear family-based association study between cystathionine-beta-synthase gene polymorphism and schizophrenia

目的:探讨胱硫醚-β-合成酶(cystathionine-beta-synthase,CBS)基因多态性与精神分裂症的关系。方法:采用聚合酶链式反应和DNA测序技术,检测75个精神分裂症核心家系CBS基因T833C、G919A多态性,采用单倍体相对风险度(haplotyperelativerisk,HRR)分析和传递不平衡检验(transmission disequilibrium test,TDT)分析CBS基因多态性与精神分裂症的关系。结果:所有受检者均未发现CBS基因T833C、G919A多态性,但下游8-9内含子33bp处见G→A突变。患者组G→A突变的基因型频率[GG(82.67%),GA(14.67%),AA(2.66%)]与父母组[GG(81.33%),GA(16%),AA(2.67%)]比较差异无统计学意义(χ2=0.29,P>0.05),患者组G→A突变的等位基因频率[G(90%),A(10%)]与父母组[G(89.33%),A(10.67%)]比较差异也无统计学意义(χ2=0.32,P>0.05)。HRR分析未显示G→A突变与精神分裂症有关联(χ2=0.21,P>0.05),TDT分析未见A等位基因在杂合双亲向患病子女的传递中有优势性(χ2=1.80,P>0.05)。结论:CBS基因多态性可能不是精神分裂症的遗传学危险因素。

Objective：To explore the relationship between cystathionine-beta-synthase（ CBS） gene polymorphism and schizophrenia. Method：The polymorphisms of CBS gene T833C,G919A were detected by polymerase chain reaction and DNA sequencing technique in 75 families trios. Haplotype relative risk（ HRR） and transmission disequilibrium test（ TDT） were used to analyze the association between CBS gene polymorphism and schizophrenia. Results：No CBS gene T833C,G919A polymorphisms were found in all subjects,but mutation of G→A was detected at the 33th base in intron 8-9. There was no significant difference in genotype frequencies of mutation of G→A between patient group[GG（ 82. 67% ） ,GA（ 14. 67% ） ,AA（ 2. 66%）] and parent group[GG（ 81. 33% ） ,GA （ 16% ） ,AA （ 2. 67% ）] （ χ2 = 0. 29,P 0. 05 ） . There was also no significant difference in allele frequencies of mutation of G→A between patient groupG（ 90% ） ,A（ 10%） and parent groupG（ 89. 33% ） ,A（ 10. 67% ） （ χ2 = 0. 32,P 0. 05） . HRR showed no association between mutation of G → A and schizophrenia（ χ2 = 0. 21,P 0. 05） . TDT analysis showed no preferential transmission of A allele from heterozygote parents to probands （ χ2 = 1. 80,P 0. 05） . Conclusion：CBS gene polymorphism may not be a genetic risk factor for schizophrenia