CAJ | 학술논문

目的探讨亚甲基四氢叶酸还原酶(methylenetet rahydro folate reductase,MTHFR)基因多态性对于抗抑郁剂疗效的影响.方法纳入281例服用单一抗抑郁药物的患者并随访6周,其中275例随访8周.使用汉密尔顿抑郁17项量表(HAMD-17)评定抑郁症状的严重程度和治疗效果.采用基因芯片检测MTHFR基因的单核苷酸多态性,并用Unphased 3.0.13软件分析单个单核苷酸多态性位点及其单倍型与抗抑郁疗效的关联性.结果 6周有效组和无效组间性别、年龄、教育程度、家族史、发病次数及抗抑郁剂种类之间差异无统计学意义,但两组间HAMD-17项基线分数有显著统计学意义(t=2.891,P=0.004);8周痊愈组和未痊愈组间年龄、教育程度、家族史、HAMD-17项基线评分及抗抑郁剂种类之间差异无统计学意义,但未痊愈组中男性患者比例显著高于痊愈组(t=2.381,P=0.018),且发病次数更多(t=-1.983,P=0.049).通过单个位点的关联分析发现,MTHFR基因位点A1298C(rs1801131)和C677T(rs1801133)与抗抑郁疗效无显著关联(P＞0.05).单倍型关联分析发现,在总体组(x2=11.39,P=0.0007)、男性亚组(x2=8.767,P=0.003)和5-羟色胺-去甲肾上腺素再摄取抑制剂亚组(x2=10.51,P=0.001)中,MTHFR基因rs1801131和rs1801133构成的单倍型A-C型抗抑郁疗效更显著.结论 MTHFR基因多态性可能与抗抑郁药疗效相关,其中rs1801131和rs1801133构成的A-C单倍型携带者抗抑郁剂疗效更为显著,尤其是在男性和使用5-羟色胺-去甲肾上腺素再摄取抑制剂类药物的人群中.
목적 탐토아갑기사경협산환원매(methylenetet rahydro folate reductase,MTHFR)기인다태성대우항억욱제료효적영향.방법 납입281례복용단일항억욱약물적환자병수방6주,기중275례수방8주.사용한밀이돈억욱17항량표(HAMD-17)평정억욱증상적엄중정도화치료효과.채용기인심편검측MTHFR기인적단핵감산다태성,병용Unphased 3.0.13연건분석단개단핵감산다태성위점급기단배형여항억욱료효적관련성.결과 6주유효조화무효조간성별、년령、교육정도、가족사、발병차수급항억욱제충류지간차이무통계학의의,단량조간HAMD-17항기선분수유현저통계학의의(t=2.891,P=0.004);8주전유조화미전유조간년령、교육정도、가족사、HAMD-17항기선평분급항억욱제충류지간차이무통계학의의,단미전유조중남성환자비례현저고우전유조(t=2.381,P=0.018),차발병차수경다(t=-1.983,P=0.049).통과단개위점적관련분석발현,MTHFR기인위점A1298C(rs1801131)화C677T(rs1801133)여항억욱료효무현저관련(P＞0.05).단배형관련분석발현,재총체조(x2=11.39,P=0.0007)、남성아조(x2=8.767,P=0.003)화5-간색알-거갑신상선소재섭취억제제아조(x2=10.51,P=0.001)중,MTHFR기인rs1801131화rs1801133구성적단배형A-C형항억욱료효경현저.결론 MTHFR기인다태성가능여항억욱약료효상관,기중rs1801131화rs1801133구성적A-C단배형휴대자항억욱제료효경위현저,우기시재남성화사용5-간색알-거갑신상선소재섭취억제제류약물적인군중.
Objective To assess influence of polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene on response to antidepressant treatment.Methods Two hundred and eight one Chinese Han patients have received single antidepressant drugs for at least 6 weeks,among whom 275 were followed up for 8 weeks.Hamilton depression scale-17 (HAMD-17) was used to evaluate the severity of depressive symptoms and therapeutic effects.Single nucleotide polymorphisms (SNPs) of the MTHFR gene was determined using gene chips.Associations of single loci and haplotypes with response to treatment were analyzed using an Unphased 3.0.13 software.Results No significant difference of gender,age,year of education,family history,episode times,and antidepressant agents was found between responders and non-responders (all P＞ 0.05),while the baseline scores of HAMD-17 was significantly different (t=2.891,P=0.004).There were also no significant difference between age,years of education,family history,baseline scores of HAMD-17 and antidepressant agents between remitters and non-remitters (both P＞0.05),while proportion of male patients was significantly higher in non-remission group than remissiongroup (t=2.381,P=0.018),and episode times in non-remission group was significantly higher (t=-1.983,P=0.049).Single locus association analysis has found no significant association between SNPs rs1801131 and rs1801133 in the MTHFR gene with antidepressant response (P＞ 0.05).On the other hand,haplotype (A-C) in MTHFR gene (rs1801131 and rs1801133) was significantly associated with antidepressant response in total group (x2 =11.39,P =0.0007),male subgroup (x2 =8.767,P =0.003)and serotonin-noradrenaline reuptake inhibitors (SNRIs) subgroup (x2=10.51,P=0.001).Conclusion Particular haplotype of MTHFR gene may be related with antidepressant effect,in which the haplotype (rs1801131-rs1801133) A-C type may be associated with better antidepressant efficacy,particularly in males and patients receiving SNRIs drugs.