BMAL1基因单核苷酸多态性与双相情感障碍的关联性研究

Association between single nucleotide polymorphism of BMAL1 and bipolar disorder

目的探讨节律基因BMAL1单核苷酸多态性(single nucleotide polymorphism,SNP)与双相情感障碍(bipolar disorder,BD)易感性及临床特征的关联性。方法采用病例对照研究,选取2018年12月至2020年1月在四川大学华西医院心理卫生中心及四川省人民医院心身医学中心门诊及住院就诊的BD患者136例和正常对照者130例,分为BD组与对照组。采用SNapShot分型技术进行外周血BMAL1基因的16个SNP位点基因分型,TT3、TT4、FT3、FT4和COR使用电化学发光定量分析进行检测,促甲状腺激素(thyroid stimulating hormone,TSH)使用ELISA法进行检测,促肾上腺皮质激素(adrenocor ticotropic hormone,ACTH)采用放射免疫分析法进行检测。统计分析节律基因BMAL1单核苷酸多态性与双相情感障碍易感性及临床特征的关联性。结果BMAL1基因的rs11022765 C、rs10832022 A和rs6486116 C等位基因携带者在BD组的分布频率均显著高于对照组(P=0.009,0.005,0.010)。rs6486116-rs10832020的CT单倍型在BD组(57.4%)分布显著高于对照组(48.5%)(P=0.040);rs10832022-rs11022765-rs11022762的GAT单倍型在BD组(30.1%)分布显著低于对照组(42.7%)(P=0.003)。rs11022765不同基因型患者的NEO-FFI外倾性因子评分有显著差异(P<0.001)。rs10832022、rs11022765不同基因型患者的HPT轴异常率均有显著差异(P=0.013,P=0.012)。结论节律基因BMAL1的SNP变异可能与BD易感性有关,且与BD特定临床表型相关联。

Objective To identify the association between single nucleotide polymorphism of rhythm gene BMAL1 and bipolar disorder(BD)of clinical characteristics and susceptibility.Methods The case-control study was conducted on 136 outpatients and inpatients with BD(the BD group)and 130 normal controls(the control group)enrolled in the Mental Health Center of West China Hospital of Sichuan University and Psychosomatic Medicine Center of Sichuan Provincial People’s Hospital from December 2018 to January 2020.Sixteen single nucleotide polymorphisms(SNPs)of BMAL1 gene were genotyped by SNapShot typing.The levels of TT3,TT4,FT3,FT4 and COR were assayed by electrochemiluminescence immunoassay.Thyroid stimulating hormone(TSH)was measured using ELISA and adrenocor ticotropic hormone(ACTH)was tested by radioimmunoassay.The association between SNPs of BMAL1 and BD of susceptibility and clinical characteristics was statistically analyzed.Results As for the distribution frequencies,allele carriers of rs1022765-C,rs10832022-A and rs6486116-C were significantly higher in BD group than those in control group(P=0.009,0.005,0.010).The haplotype analysis showed that the distribution frequency of rs6486116-rs10832020 C-T haplotype in BD group(57.4%)was significantly higher than that in control group(48.5%)(P=0.040);the distribution frequency of rs10832022-rs11022765-rs11022762 G-A-T haplotype was significantly lower in BD group(30.1%)than that in control group(42.7%)(P=0.003).Through multiple logistic regression,the extroversion factor scores of NEO-FFI among patients with different genotypes of rs11022765 were significantly different(P<0.001).Meanwhile,the incidences of the abnormal HPT axis among patients with different genotypes of both rs10832022 and rs11022765 were also significantly different(P=0.013,P=0.012).Conclusion SNPs of BMAL1 is associated with the susceptibility of BD,and also associated with clinical phenotypes.