五羟色胺转运体基因多态性与青少年创伤后应激障碍的相关性研究
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摘要
目的研究五羟色胺转运体基因可变数目串联重复序列(5-HTTVNTR)多态性与汶川地震后青少年患创伤后应激障碍(PTSD)之间是否具有关联性,探讨PTSD发病的遗传学机制。方法用聚合酶链式反应(PCR)对地震灾区236例PTSD阳性和234例正常对照青少年的5-HTTVNTR基因多态性进行分型,用PLINK(v1.07)软件对基因分型结果进行统计分析。结果 5-HTTVNTR等位基因12在PTSD组中的分布频率高于对照组(93.2%vs.88.9%,χ2=5.42,P=0.020);12/12基因型的频率在PTSD组和对照组中分别为88.1%、79.7%,10/12基因型的频率分别为10.2%、19.6%,10/10基因型的频率均为1.7%,3种基因型(12/12、10/12、10/10)在两组中的分布频率差异具有统计学意义(P=0.023)。结论 5-HTTVNTR等位基因12可能会增加中国汉族青少年患PTSD的风险,12/12纯合子可能是其患PTSD的易感基因型,10/12杂合子可能是其患PTSD的保护因子。
Objective To study the association between 5-HTTVNTR polymorphism and posttraumatic stress disorder(PTSD) in Chinese Han adolescents after the Wenchuan Earthquake,and investigation of the genetic mechanism of PTSD.Methods Polymerase chain reaction(PCR) was used to detect the distributive frequency of 5-HTTVNTR polymorphism of 236 PTSD patients(patient group) and 234 normal people(control group),Plink version 1.07 was used to analyze the genotyping results.Results The frequency of 5-HTTVNTR allele 12 in PTSD group was significantly higher than control group(93.2% vs.88.9%,χ2=5.42,P=0.020).The 12/12 genotype in PTSD group and control group was 88.1% and 79.7%;10/12 genotype was 10.2% and 19.6%;10/10 genotype was 1.7% and 1.7%.The distributive frequency of all three genotypes(12/12,10/12,10/10) showed statistically significant(P=0.023).Conclusion The allele 12 of 5-HTTVNTR may increase the risk of PTSD in Chinese Han adolescents,12/12 genotype may be the susceptibility gene,and heterozygote 10/12 may act as the protective factor of PTSD.
Objective To study the association between 5-HTTVNTR polymorphism and posttraumatic stress disorder(PTSD) in Chinese Han adolescents after the Wenchuan Earthquake,and investigation of the genetic mechanism of PTSD.Methods Polymerase chain reaction(PCR) was used to detect the distributive frequency of 5-HTTVNTR polymorphism of 236 PTSD patients(patient group) and 234 normal people(control group),Plink version 1.07 was used to analyze the genotyping results.Results The frequency of 5-HTTVNTR allele 12 in PTSD group was significantly higher than control group(93.2% vs.88.9%,χ2=5.42,P=0.020).The 12/12 genotype in PTSD group and control group was 88.1% and 79.7%;10/12 genotype was 10.2% and 19.6%;10/10 genotype was 1.7% and 1.7%.The distributive frequency of all three genotypes(12/12,10/12,10/10) showed statistically significant(P=0.023).Conclusion The allele 12 of 5-HTTVNTR may increase the risk of PTSD in Chinese Han adolescents,12/12 genotype may be the susceptibility gene,and heterozygote 10/12 may act as the protective factor of PTSD.
引文
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2 Lee HJ,Lee MS,Kang RH,et al.Influence of the serotonintransporter promoter gene polymorphism on susceptibility toposttraumatic stress disorder.Depress Anxiety,2005;21(3):135-139.
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4 Kilpatrick DG,Koenen KC,Ruggiero KJ,et al.The serotonintransporter genotype and social support and moderation ofposttraumatic stress disorder and depression in hurricane-exposed adults.Am J Psychiatry,2007;164(11):1693-1699.
5 Mellman TA,Alim T,Brown DD,et al.Serotoninpolymorphisms and posttraumatic stress disorder in a traumaexposed African American population.Depress Anxiety,2009;26(11):993-997.
6 Yue W,Liu H,Zhang J,et al.Association study of serotonintransporter gene polymorphisms with obstructive sleep apneasyndrome in Chinese Han population.Sleep,2008;31(11):1535-1541.
7 Purcell S,Neale B,Todd-Brown K,et al.PLINK:a tool setfor whole-genome association and population-based linkageanalyses.Am J Hum Genet,2007;81(3):559-575.
8 Jans LA,Riedel WJ,Markus CR,et al.Serotonergicvulnerability and depression:assumptions,experimentalevidence and implications.Mol Psychiatry,2007;12(6):522-543.
9 Kolassa IT,Ertl V,Eckart C,et al.Association study oftrauma load and SLC6A4 promoter polymorphism inposttraumatic stress disorder:evidence from survivors of theRwandan genocide.J Clin Psychiatry,2010;71(5):543-547.
10 MacKenzie A,Quinn J.A serotonin transporter gene intron 2polymorphic region,correlated with affective disorders,hasallele-dependent differential enhancer-like properties in themouse embryo.Proc Natl Acad Sci USA,1999;96(26):15251-15255.
11 Perrin BJ,Amann KJ,Huttenlocher A.Proteolysis ofcortactin by calpain regulates membrane protrusion during cellmigration.Mol Biol Cell,2006;17(1):239-250.
12 Perrin CL,Erdelyi M.One-bond C-C coupling constants inethers are not primarily determined by N-sigma delocalization.J Am Chem Soc,2005;127(17):6168-6169.
13 Dri P,Calmi S.If big tobacco cries,big pharma laughs.Epidemiol Prev,2005;29(1):5.
14 Perrin EM,Flower KB,Ammerman AS.Pediatricians’ownweight:self-perception,misclassification,and ease ofcounseling.Obes Res,2005;13(2):326-332.
15 Amstadter AB,Koenen KC,Ruggiero KJ,et al.Variant inRGS2 moderates posttraumatic stress symptoms followingpotentially traumatic event exposure.J Anxiety Disord,2009;23(3):369-373.
16 Lotrich FE,Pollock BG.Meta-analysis of serotonintransporter polymorphisms and affective disorders.PsychiatrGenet,2004;14(3):121-129.
17 Florez G,Saiz P,Garcia-Portilla P,et al.Association betweenthe Stin2 VNTR polymorphism of the serotonin transportergene and treatment outcome in alcohol-dependent patients.Alcohol Alcohol,2008;43(5):516-522.
18 Kaiser R,Tremblay PB,Schmider J,et al.Serotonintransporter polymorphisms:no association with response toantipsychotic treatment,but associations with theschizoparanoid and residual subtypes of schizophrenia.MolPsychiatry,2001;6(2):179-185.
19 Fan JB,Sklar P.Meta-analysis reveals association betweenserotonin transporter gene STin2 VNTR polymorphism andschizophrenia.Mol Psychiatry,2005;10(10):928-938,891.
20 Rothe C,Koszycki D,Bradwejn J,et al.Association study ofserotonin-2Areceptor gene polymorphism and panic disorder inpatients from Canada and Germany.Neurosci Lett,2004;363(3):276-279.
21 Xie P,Kranzler HR,Poling J,et al.Interactive effect ofstressful life events and the serotonin transporter 5-HTTLPRgenotype on posttraumatic stress disorder diagnosis in 2independent populations.Arch Gen Psychiatry,2009;66(11):1201-1209.
22 Rainnie DG.Serotonergic modulation of neurotransmission inthe rat basolateral amygdala.J Neurophysiol,1999;82(1):69-85.
2 Lee HJ,Lee MS,Kang RH,et al.Influence of the serotonintransporter promoter gene polymorphism on susceptibility toposttraumatic stress disorder.Depress Anxiety,2005;21(3):135-139.
3 Grabe HJ,Spitzer C,Schwahn C,et al.Serotonin transportergene(SLC6A4)promoter polymorphisms and the susceptibilityto posttraumatic stress disorder in the general population.AmJ Psychiatry,2009;166(8):926-933.
4 Kilpatrick DG,Koenen KC,Ruggiero KJ,et al.The serotonintransporter genotype and social support and moderation ofposttraumatic stress disorder and depression in hurricane-exposed adults.Am J Psychiatry,2007;164(11):1693-1699.
5 Mellman TA,Alim T,Brown DD,et al.Serotoninpolymorphisms and posttraumatic stress disorder in a traumaexposed African American population.Depress Anxiety,2009;26(11):993-997.
6 Yue W,Liu H,Zhang J,et al.Association study of serotonintransporter gene polymorphisms with obstructive sleep apneasyndrome in Chinese Han population.Sleep,2008;31(11):1535-1541.
7 Purcell S,Neale B,Todd-Brown K,et al.PLINK:a tool setfor whole-genome association and population-based linkageanalyses.Am J Hum Genet,2007;81(3):559-575.
8 Jans LA,Riedel WJ,Markus CR,et al.Serotonergicvulnerability and depression:assumptions,experimentalevidence and implications.Mol Psychiatry,2007;12(6):522-543.
9 Kolassa IT,Ertl V,Eckart C,et al.Association study oftrauma load and SLC6A4 promoter polymorphism inposttraumatic stress disorder:evidence from survivors of theRwandan genocide.J Clin Psychiatry,2010;71(5):543-547.
10 MacKenzie A,Quinn J.A serotonin transporter gene intron 2polymorphic region,correlated with affective disorders,hasallele-dependent differential enhancer-like properties in themouse embryo.Proc Natl Acad Sci USA,1999;96(26):15251-15255.
11 Perrin BJ,Amann KJ,Huttenlocher A.Proteolysis ofcortactin by calpain regulates membrane protrusion during cellmigration.Mol Biol Cell,2006;17(1):239-250.
12 Perrin CL,Erdelyi M.One-bond C-C coupling constants inethers are not primarily determined by N-sigma delocalization.J Am Chem Soc,2005;127(17):6168-6169.
13 Dri P,Calmi S.If big tobacco cries,big pharma laughs.Epidemiol Prev,2005;29(1):5.
14 Perrin EM,Flower KB,Ammerman AS.Pediatricians’ownweight:self-perception,misclassification,and ease ofcounseling.Obes Res,2005;13(2):326-332.
15 Amstadter AB,Koenen KC,Ruggiero KJ,et al.Variant inRGS2 moderates posttraumatic stress symptoms followingpotentially traumatic event exposure.J Anxiety Disord,2009;23(3):369-373.
16 Lotrich FE,Pollock BG.Meta-analysis of serotonintransporter polymorphisms and affective disorders.PsychiatrGenet,2004;14(3):121-129.
17 Florez G,Saiz P,Garcia-Portilla P,et al.Association betweenthe Stin2 VNTR polymorphism of the serotonin transportergene and treatment outcome in alcohol-dependent patients.Alcohol Alcohol,2008;43(5):516-522.
18 Kaiser R,Tremblay PB,Schmider J,et al.Serotonintransporter polymorphisms:no association with response toantipsychotic treatment,but associations with theschizoparanoid and residual subtypes of schizophrenia.MolPsychiatry,2001;6(2):179-185.
19 Fan JB,Sklar P.Meta-analysis reveals association betweenserotonin transporter gene STin2 VNTR polymorphism andschizophrenia.Mol Psychiatry,2005;10(10):928-938,891.
20 Rothe C,Koszycki D,Bradwejn J,et al.Association study ofserotonin-2Areceptor gene polymorphism and panic disorder inpatients from Canada and Germany.Neurosci Lett,2004;363(3):276-279.
21 Xie P,Kranzler HR,Poling J,et al.Interactive effect ofstressful life events and the serotonin transporter 5-HTTLPRgenotype on posttraumatic stress disorder diagnosis in 2independent populations.Arch Gen Psychiatry,2009;66(11):1201-1209.
22 Rainnie DG.Serotonergic modulation of neurotransmission inthe rat basolateral amygdala.J Neurophysiol,1999;82(1):69-85.
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