MSRA基因rs4840463多态性对双相障碍Ⅰ型眶额叶皮质体积的影响

Effect of MSRA rs4840463 gene polymorphism on orbitofrontal cortex volume in patients with bipolar disor⁃der typeⅠ.

目的探索抗氧化酶甲硫氨酸亚砜还原酶A(methionine sulfoxide reductase A,MSRA)基因rs4840463多态性对中国汉族成年双相障碍Ⅰ型(bipolarⅠdisorder,BD-Ⅰ)患者眶额叶皮质(orbitofrontal cortex,OFC)体积的影响。方法纳入87例BD-Ⅰ患者和82名性别、年龄相匹配的健康对照(healthy control,HC),进行磁共振扫描和MSRA基因rs4840463多态性检测,采用一般线性模型分析rs4840463多态性与疾病诊断对OFC各亚区体积的交互作用。结果MSRA基因rs4840463多态性和BD-Ⅰ诊断对左右外侧OFC体积的交互作用均有统计学意义(左外侧P=0.030,右外侧P=0.002)。即在BD-Ⅰ患者中,与非风险A等位基因携带者相比,风险A等位基因携带者右外侧OFC体积更小[(7367.52±809.88)mm^(3)vs.(7576.48±906.38)mm^(3),P=0.014];在MSRA基因rs4840463风险A等位基因携带者中,与HC组相比,BD-Ⅰ组左右外侧OFC体积更小[左外侧,(7535.67±809.39)mm^(3)vs.(8012.69±838.59)mm^(3),P=0.014;右外侧,(7367.52±809.88)mm^(3)vs.(8024.04±915.31)mm^(3),P=0.004]。结论MSRA基因作为BD风险基因,其rs4840463位点的风险A等位基因与BD-Ⅰ患者OFC体积减小相关。

Objective To explore the effect of methionine sulfoxide reductase A(MSRA)rs4840463 gene polymorphism on the volume of orbitofrontal cortex(OFC)in Chinese Han adults with bipolar disorder typeⅠ(BD-Ⅰ).Methods Magnetic resonance imaging and MSRA rs4840463 gene polymorphism were detected in 87 patients with BD-Ⅰand 82 age-matched healthy controls(HC).The interaction between rs4840463 polymorphism and diagnosis for the volume of OFC subregions was analyzed by general linear model.Results We found a significant interaction between MSRA rs4840463 gene polymorphism and diagnosis for the left and right lateral OFC volume(left lateral P=0.030,left lateral P=0.002).Bonferroni corrected post-hoc tests revealed that,in BD-Ⅰpatients,MSRA rs4840463 risk A-allele carriers exhibited reduced right lateral OFC volume compared to CC-allele carriers[(7367.52±809.88)mm^(3)vs.(7576.48±906.38)mm^(3),P=0.014].While in MSRA rs4840463 risk A-allele carriers,BD-Ⅰpatients displayed reduced left and right lateral OFC volume compared to HC[left lateral,(7535.67±809.39)mm^(3)vs.(8012.69±838.59)mm^(3),P=0.014;right lateral,(7367.52±809.88)mm^(3)vs.(8024.04±915.31)mm^(3),P=0.004].Conclusion The present study has demonstrated that the MSRA rs4840463 risk A-allele,as a risk gene for bipolar disorder,is associated with the decrease of OFC volume in patients with BD-Ⅰ,suggesting the relationship between antioxidant enzyme gene and neuropathological mechanism of BD.