抑郁症与双相障碍患者昼夜节律通路基因多态性的差异分析  

Differential analysis of circadian rhythm pathway gene polymorphisms in patients with depression and bipolar disorder

作　　者：陈磊 陈子木 沈甜 谈婷婷 高晨洁 陈素珍[1] 陈炳为[2] 袁勇贵[1] 张志珺[3] 徐治[1] Chen Lei;Chen Zimu;Shen Tian;Tan Tingting;Gao Chenjie;Chen Suzhen;Chen Bingwei;Yuan Yonggui;Zhang Zhijun;Xu Zhi(Department of Psychosomatics and Psychiatry,Zhongda Hospital,School of Medicine,Southeast University,Nanjing 210009,China;Department of Epidemiology and Biostatistics,School of Public Health,Southeast University,Nanjing 210009,China;Department of Neurology,Zhongda Hospital,School of Medicine,Southeast University,Nanjing 210009,China;The Psychiatry Department of the General Hospital of Eastern Theater Command,Jinling Hospital,Nanjing University School of Medicine,Nanjing 210002,China)

机构地区：[1]东南大学附属中大医院心理精神科,南京210009 [2]东南大学公共卫生学院,南京210009 [3]东南大学医学院附属中大医院神经内科,南京210009 [4]东部战区总医院南京大学医学院附属金陵医院精神心理科工作,南京210002

出　　处：《中华精神科杂志》2024年第8期495-501,共7页Chinese Journal of Psychiatry

基　　金：国家自然科学基金(82371534);江苏省青年医学重点人才(QNRC2016825);江苏省自然科学基金(BK20181272)。

摘　　要：目的探究抑郁症和双相障碍患者昼夜节律通路基因多态性的差异,以为两者的鉴别诊断提供遗传学依据。方法前瞻性收集2012至2018年在东南大学附属中大医院住院的70例5年随访间一直诊断为抑郁症的患者(简称抑郁症组)和68例诊断为双相障碍的患者(简称双相障碍组)。选取昼夜节律通路基因单核苷酸多态性(single nucleotide polymorphisms,SNPs)进行昼夜节律通路基因检测,分析每个SNP的基因型频率、等位基因频率和单倍型在抑郁症和双相障碍间的差异。结果基因型频率分析发现,2组患者中的PER1rs2253820、PER1rs2735611、PER3rs12566042、PER3rs17031614、PER3rs79372391基因型频率的差异有统计学意义[OR(95%CI)分别为2.386(1.173~4.854)、2.357(1.166~4.764)、0.351(0.176~0.703)、0.389(0.196~0.773)、0.389(0.196~0.773);均P<0.05];单倍型分析发现,CLOCK位点rs12505266、rs2272073、rs3817444、rs11133389和rs12505265构成的单倍型中,T-C-C-T-G单倍型在2组患者中的差异有统计学意义[OR(95%CI)=0.108(0.010~1.185),P=0.027]。结论昼夜节律基因多态性在抑郁症和双相障碍患者间差异具有统计学意义,携带PER1rs2253820TT、PER1rs2735611GG基因型是双相障碍的危险因素。ObjectiveTo explore the differences of the circadian rhythm gene polymorphisms between patients with major depressive disorder and those with bipolar disorder,providing a genetic basis for differential diagnosis.Methods70 patients who were still diagnosed with major depressive disorder after 5 years and 68 patients who were still diagnosed with bipolar disorder from Zhongda Hospital affiliated to Southeast University from 2012 to 2018 were included in this study.Single nucleotide polymorphisms(SNPs)of circadian rhythm gene were selected for genetic testing.And the differences in genotype frequency,allele frequency,and haplotypes of each SNP between major depressive disorder and bipolar disorder were analyzed using UNPHASED 3.1.7.ResultsThe analysis of genotype frequency revealed statistically significant differences in genotype frequency of PER1rs2253820,PER1rs2735611,PER3rs12566042,PER3rs17031614,and PER3rs79372391 between the two groups(OR(95%CI)=2.386(1.173-4.854),2.357(1.166-4.764),0.351(0.176-0.703),0.389(0.196-0.773),0.389(0.196-0.773)respectively;all P<0.05).Haplotype analysis showed that the T-C-C-T-G haplotype,in CLOCK loci(rs12505266,rs2272073,rs3817444,rs11133389 and rs12505265)was significantly different between major depressive disorder group and bipolar disorder group(OR(95%CI)=0.108(0.010-1.185),P=0.027).ConclusionThere are significant differences in circadian rhythm gene polymorphisms between patients with major depressive disorder and bipolar disorder.Carrying the PER1rs2253820TT and PER1rs2735611GG genotypes is a risk factors for bipolar disorder.

关 键 词：抑郁症 双相情感障碍 昼夜节律通路基因 多态性 

分 类 号：R749.4[医药卫生—神经病学与精神病学]