TPH2基因单核苷酸多态性与情感性精神障碍及其自杀行为的关系

[目的]探讨色氨酸羟化酶2(TPH2)基因rs7305115单核苷酸多态性与情感障碍及自杀行为的关系。[方法]提取402例情感障碍患者和225名健康对照者基因组DNA,采用聚合酶链反应(polymerase chain reactionPCR)扩增含TPH2基因rs7305115位点的312bp基因组DNA片段,并将PCR产物直接测序。[结果]在第7外显子周围未发现其他的单核苷酸多态性。情感障碍患者和健康对照者TPH2rs7305115基因型和等位基因频率差异无统计学意义(P﹥0.05),但患者组内有自杀行为的个体携带基因型AA的频率及等位基因A的频率均较低,差异有统计学意义(P﹤0.01)。[结论]TPH2基因rs7305115单核苷酸多态性与情感障碍无明显关联,与自杀行为有关联,其可能与情感障碍自杀行为易感性相关。     

TPH2基因多态性与单相抑郁及自杀行为关系

目的探讨色氨酸羟化酶2(TPH2)基因rs4570625位点单核苷酸多态性与单相抑郁症及自杀行为的关系。方法提取中国北方地区300例单相抑郁患者(病例组)和300名健康对照者(对照组)基因组DNA,采用聚合酶链反应技术(PCR)扩增包含TPH2基因rs4570625位点的基因组DNA片段,将PCR产物直接测序检测病例组及对照组的基因型,应用SPSS 11.0软件进行统计分析。结果病例组与对照组SNPs基因型分布符合Hardy-Weinberg平衡定律(P>0.05);单相抑郁症组与健康对照组TPH2 rs4570625基因型及等位基因频率比较,差异无统计学意义。病例组有自杀行为组携带的基因型T/T、G/G、T/G频率分别为31.3%(30/96)、18.8%(18/96)、46.9%(45/96),无自杀行为组分别为23.0%(47/204)、27.5%(56/204)、42.6%(87/204),2组比较差异无统计学意义;有自杀行为组TPH2基因rs4570625位点等位基因T、G频率分别为56.5%(105/186)、43.5%(81/186),无自杀行为组分别为47.6%(181/380)、52.4%(199/380),2组比较差异有统计学意义(χ2=3.886,P=0.049)。结论TPH2基因rs4570625单核苷酸多态性与单相抑郁症无明显关联,与抑郁症自杀行为易感性有关。     

215例抑郁症患者自杀未遂危险因素的配对病例对照研究

目的了解汉族人群抑郁症患者自杀未遂的环境危险因素、色氨酸羟化酶2(TPH2)基因rs7305115单核苷酸多态性与自杀未遂有无关联。方法采用配对病例对照研究,对215例自杀未遂者(男性92例、女性123例)与相应对照(与病例同性别、年龄相差3岁以内、同地区)进行TPH2 rs7305115基因型测定、自杀行为干预研究量表调查环境因素与抑郁症自杀未遂的关系研究。结果研究组与对照组在TPH2 rs7305115基因型、基因频率的差异有统计学意义(P<0.001);多因素条件logistic回归模型分析显示,绝望、负性生活事件、有自杀家族史,均为抑郁症自杀未遂危险因素,OR值分别为7.68(95%CI:5.79-13.74)、6.64(95%CI:2.48-11.04)、2.98(95%CI:1.17-5.04); TPH2 rs7305115 A/A为抑郁症自杀未遂的保护因素0.33(95%CI:0.22-0.99)。结论绝望、负性生活事件、自杀家族史是抑郁症自杀未遂的危险因素,TPH2 rs7305115 A/A可能是抑郁症自杀行为的保护因素。     

TPH2 rs11178997基因多态性与女性抑郁及自杀行为的关联性分析

目的:探讨色氨酸羟化酶2(TPH2)基因rs11178997单核苷酸多态性与女性单相抑郁症及自杀行为的关系。方法:提取中国北方地区219例女性单相抑郁患者(病例组)和215名健康对照者(对照组)基因组DNA,采用TaqMan探针SNP基因分型技术测定包含TPH2基因rs11178997位点的基因组DNA片段,检测病例组及对照组基因型的多态分布,应用SPSS17.0软件进行统计分析。结果:病例组与对照组SNPs基因型分布符合Hardy-Weinberg平衡定律(P>0.05);病例组携带的TPH2 rs11178997基因型A/A、G/G、A/G频率分别为73.52%(161/219)、7.30%(16/219)和19.18%(42/219),对照组分别为38.60%(83/215)、60.00%(129/215)、1.40%(3/215),两组比较差异有统计学意义(χ2=146.772,P=0.000);病例组TPH2 rs11178997等位基因A、G频率分别为83.10%(364/438)、16.89%(74/438),对照组分别为39.30%(169/430)、60.70%(261/430),两组比较差异有统计学意义(χ2=175.668,P=0.000);病例组内有自杀行为的个体携带TPH2 rs11178997基因型A/A、G/G、A/G的频率及等位基因A、G频率比较差异均无统计学意义(P>0.05)。结论:TPH2基因rs11178997单核苷酸多态性与女性单相抑郁症有明显关联,可能与女性抑郁症自杀行为易感性无关。     

TPH2基因多态性与单相抑郁及自杀行为关系

目的 探讨色氨酸羟化酶2(TPH2)基因G1463A单核苷酸多态性与单相抑郁症及自杀行为的关系.方法 提取中国北方地区300例单相抑郁患者(病例组)和292名健康对照者(对照组)基因组DNA,采用TaqMan探针SNP基因分型技术测定包含TPH2基因G1463A位点的基因组DNA片段,检测病例组及对照组基因型的多态分布,应用SPSS 17.0软件进行统计分析.结果 病例组与对照组SNPs基因型分布符合Hardy-Weinberg平衡定律(P＞0.05)；病例组携带的TPH2 G1463A基因型A/A、T/T、A/T频率分别为38.0％ (114/300)、0.3％(1/300)和61.7％(185/300),对照组分别为50.0％(146/292)、40.1％(117/292)、9.9％(29/292),2组比较差异有统计学意义(x2 =231.626,P=0.000)；病例组TPH2基因G1463A等位基因A、T频率分别为68.8％ (413/600)、31.2％(187/600),对照组分别为55.0％ (321/584)、45.0％(263/584),2组比较差异有统计学意义(x2=24.155,P =0.000)；病例组TPH2基因G1463A不同基因型的汉密尔顿抑郁量表(HAMD)总分及各因子得分比较差异均有统计学意义(P=0.000)；病例组内有自杀行为的个体携带基因型A/A、T/T、A/T的频率及G1463A位点等位基因A、T频率比较差异均无统计学意义(P＞0.05).结论 TPH2基因G1463A单核苷酸多态性与单相抑郁症有明显关联,可能与抑郁症自杀行为易感性无关.     

TPH2G1463A基因多态性与女性抑郁及自杀行为的关联研究

目的:探讨色氨酸羟化酶2(TPH2)基因G1463A单核苷酸多态性与女性单相抑郁症及自杀行为的关系。方法:提取中国北方地区219例女性单相抑郁患者(病例组)和215名健康对照者(对照组)基因组DNA,采用TaqMan探针SNP基因分型技术测定包含TPH2基因G1463A位点的基因组DNA片段,检测病例组及对照组基因型的多态分布,应用SPSS 17.0软件进行统计分析。结果:病例组与对照组SNPs基因型分布符合Hardy-Weinberg平衡定律(P>0.05);病例组携带的TPH2G1463A基因型A/A、T/T、A/T频率分别为38.36%(84/219)、0.46%(1/219)和61.19%(134/219),对照组分别为48.37%(104/215)、40.00%(86/215)、11.63%(25/215),两组比较差异有统计学意义(χ2=159.874,P=0.000);病例组TPH2 G1463A等位基因A、T频率分别为68.95%(302/438)、31.05%(136/438),对照组分别为54.19%(233/430)、45.81%(197/430),两组比较差异有统计学意义(χ2=20.001,P=0.000);病例组内有自杀行为的个体携带TPH2 G1463A基因型A/A、T/T、A/T的频率及等位基因A、T频率比较差异均无统计学意义(P>0.05)。结论:TPH2基因G1463A单核苷酸多态性与女性单相抑郁症有明显关联,可能与女性抑郁症自杀行为易感性无关。     

辐射诱发胸腺淋巴瘤与Ikaros及p16基因多态性

目的 探讨Ikaros及p16基因多态性与辐射诱发小鼠胸腺淋巴瘤的相关性.方法 采用Promega公司基因组DNA纯化试剂盒提取胸腺淋巴瘤细胞基因组DNA.采用聚合酶链式反应-限制性片段长度多态性(PCR-PEEP)方法检测Ikaros基因rs28185870位点(C/T)、rs28185923位点(C/T)及p16基因rs3695947位点(A/G)单核苷酸多态性(SNPs).结果 C57BL/6J及BALB/c小鼠rs28185870位点基因型分别为T/T、C/C;rs28185923位点基因型分别为C/C、T/T;rs3695947位点基因型分别为A/A、G/G.结论 辐射敏感性不同的C57BL/6J、BALB/c小鼠的rs28185870、rs28185923及rs3695947位点基因型不同,推测Ikaros及p16基因多态性与辐射诱发胸腺淋巴瘤相关.     

广州番禺区汉族人群2型糖尿病与Preproghrelin基因rs96217位点单核苷酸多态性关系分析

目的探讨广州番禺区汉族人群2型糖尿病与Preproghrelin基因rs96217位点单核苷酸多态性的关系。方法随机抽取广州番禺区汉族人群中120例2型糖尿病患者为研究组,120例健康正常人为对照组。采集两组研究对象的DNA,通过PCR-RFLP,对两组研究对象的Preproghrelin基因rs96217位点的基因型及组间基因型等进行对比分析。结果研究组120例样本中,90例CC,基因型频率为0.750;26例AC,基因型频率为0.217;4例AA,基因型频率为0.033。对照组120例样本中,99例CC,基因型频率为0.825;21例AC,基因型频率为0.175;0例AA,基因型频率为0.00%。组间基因型与等位基因频率对比,结果无统计学差异(P﹥0.05)。结论广州番禺区汉族人群2型糖尿病与Preproghrelin基因rs96217位点单核苷酸多态性之间无统计学差异,但2型糖尿病患者存在AA基因型,健康正常人未显示,应在今后进行更为深入的研究。     

DDB2基因单核苷酸多态性与焦炉工外周血淋巴细胞DNA损伤的关联

[目的]探讨DDB2基因单核苷酸多态性与焦炉工外周血淋巴细胞DNA损伤的关联。[方法]选取焦化厂在岗焦炉工325名作为接触组,选择同厂无职业多环芳烃暴露者150人作为对照组,使用反向高效液相色谱法测定尿1-羟基芘含量,采用碱性单细胞凝胶电泳技术检测淋巴细胞DNA损伤情况,应用TaqMan探针荧光标记聚合酶链反应方法对DDB2基因进行分型。[结果]接触组尿1-羟基芘含量[（4.41±1.06）μmol/mol肌酐]高于对照组[（3.33±1.03）μmol/mol肌酐],差异有统计学意义（P〈0.05）;接触组外周血淋巴细胞彗星尾距（olive tail moment,OTM）[0.41（0.08～4.28）]也高于对照组[0.31（0.08～3.16）],差异有统计学意义（P〈0.05）。两组中DDB2基因SNPs的不同基因型携带者OTM差异均无统计学意义。分层结果表明,对照组年龄〈39岁个体中,启动子区rs2029298位点AA基因型携带者DNA损伤高于GG基因型携带者,差异有统计学意义（P〈0.05）;其他差异均无统计学意义。[结论]DDB2基因多态性对焦炉工外周血淋巴细胞DNA损伤程度无影响,在对照组低年龄个体中rs2029298位点AA基因型携带者的DNA损伤程度高于GG基因型携带者。     

ACE基因和AT1R基因多态性与2型糖尿病早期肾病相关性的研究

[目的]探讨ACE和AT1R基因多态性与2型糖尿病肾病的相互关系,从分子水平揭示发病机制。[方法]应用多聚酶链反应(PCR)结合限制性酶切技术,检测40例正常人和60例2型糖尿病患者ACE、AT1R的基因型和等位基因频率。[结果]①糖尿病(DM)组与糖尿病肾病(DN)组间的AT1R基因型构成和等位基因频率差异均无统计学意义(χ2=0.017,P﹥0.05;χ2=0.012,P﹥0.05)。DM组与DN组分别同对照组相比AT1R基因型构成差异均有统计学意义(χ2=8.40,P﹤0.01;χ2=7.06,P﹤0.01);等位基因频率差异也均有统计学意义(χ2=7.14,P﹤0.01;χ2=6.11,P﹤0.05);②DM组、DN组与对照组3组之间ACE基因型构成、等位基因频率差异均无统计学意义(P﹥0.05);③糖尿病肾病患者每分钟尿白蛋白排泄率与ACE和AT1R基因多态性可能无明显相关性(P﹥0.05)。[结论]ACE基因的DD基因型和D等位基因可能不是2型糖尿病及糖尿病肾病发生的危险因子;AT1R基因的C等位基因是2型糖尿病及糖尿病肾病发生的危险因子;D和C等位基因可能不是糖尿病肾病患者出现蛋白尿的危险因素。     

Tryptophan hydroxylase polymorphism is associated with age of onset of alcoholism related behaviors.

The purpose of this study was to explore the association of a tryptophan hydroxylase gene polymorphism (TPH1 A218C) with the age of alcoholism onset in a Korean population. The genotype and allele frequencies of TPH1 were investigated in 182 male hospitalized patients who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for alcohol dependence. Alcoholics with the TPH1 AA or AC genotypes had an earlier age of disease onset (median age of onset, 26.5 years) than those with the CC genotype (median age of onset, 30 years; p=.002). Age of onset has been used in classifying alcoholics. The TPH1 polymorphism may explain, in part, the biological basis for these typologies.     

Impact of amino acid imbalance on brain amines

The brain levels of serotonin (5-HT), norepinephrine (NE) and dopamine (DM) were studied in amino acid imbalance, induced in rats by feeding them an 8% casein diet supplemented with 0.3% L-threonine. In addition, tryptophan hydroxylase (TPH) and monoamine oxidase (MAO) activities in the brain were measured. The studies revealed that induction of amino acid imbalance decreased the brain levels of 5-HT and NE, and increased the DM level significantly. These changes in the amine levels were found to be accompanied by increases in the activities of TPH and MAO of brain. It has been suggested that the enhanced activity of brain TPH in threonine imbalance was probably brought about by a conformational change of the enzyme protein and might be an adaptive response to the low level of 5-HT in the brain due to increased MAO activity. The increased brain DM level in threonine imbalance could be ascribed to enhanced entry of tyrosine in the catecholamine anabolic pathway, while the diminished brain NE level under the same condition might result from its increased degradation or diminished conversion of DM to NE due to supposedly inhibition of DM-beta-hydroxylase.     

FTO和MC4R基因多态性与代谢综合征相关性状的关联研究

目的探讨FTO基因rs9939609多态性和MC4R基因rs12970134多态性与代谢综合征相关性状之间的相关性。方法从北京市18～79岁常住居民中选取983人,包括肥胖组441名,对照组542名。通过问卷调查、代谢综合征相关性状测量和基因多态性测定,对两个基因多态性和代谢综合征相关性状进行关联分析。结果携带FTO基因rs9939609多态性A等位基因者发生代谢综合征的风险增加为1.53倍(95%CI:1.08～2.15,P=0.02)。携带MC4R基因rs12970134多态性A等位基因者发生肥胖的风险增加为1.42倍(95%CI:1.09～1.84,P=0.01)。每个rs12970134多态性A等位基因使血糖升高0.17mmol/L(95%CI:0.03～0.32,P=0.02)。携带两个以上FTO或MC4R风险等位基因者与没有携带风险等位基因者相比,肥胖发生风险增加为2.04倍(95%CI:1.25～3.33,P=0.004)。结论 FTO基因rs9939609多态性和MC4R基因rs12970134多态性在中国成人中与代谢综合征相关性状存在关联,可为代谢综合征的预防和控制提供理论依据。     

hsp60基因多态性在中国汉族人中的分布

目的 检测中国汉族人热休克蛋白60（heat shock protein 60,hsp60）基因调控区和编码区的单核苷酸多态性（single nucleotide polymorphisms,SNPs）,寻找hsp60基因的遗传标记.方法 采用分片段扩增直接测序的方法检测60名汉族人hsp60基因的5＇侧翼区、部分编码区和内含子区,将测序结果与美国国家生物技术信息中心（National Center for Biotechnology Information,NCBI）及国际人类基因组单体型图计划（International HapMap Project,HapMap）中日本人、欧洲人及非洲人的序列进行对比,确定中国汉族人群hsp60基因SNPs的位置、类型和频率.结果 在hsp60基因2号外显子区发现1个新的同义SNP,位于2号染色体198189061位,最小等位基因频率（the minor allele frequency,MAF）为0.025.检测区域内包含11个已报道的SNPs,7个未在研究人群中检出;4个被检出的SNPs为rs1116734、rs3749095、rs1050347、rs8539,MAF分别为0.51、0.30、0.29、0.49;rs1116734、rs1050347、rs8539在日本人和中国汉族人群中的分布相似;rs3749095在中国汉族人中较常见,在日本人种中未检出;rs8539在欧洲及非洲人中的分布与在中国人的分布差异有统计学意义（P＜0.01）.结论 中国汉族人群hsp60的SNPs分布有别于其他人种,rs1116734、rs3749095、rs1050347、rs8539是hsp60基因在中国汉族人群中较常见的SNPs,可为Hsp60蛋白功能研究及hsp60基因与疾病关联研究候选SNPs的选择提供科学依据.     

Association between smoking habits and tryptophan hydroxylase gene C218A polymorphism among the Japanese population

BACKGROUND: Genetic polymorphisms have proposed a new insight in smoking behavior. Genes in serotonin system are one of the candidates because of serotonin's role in mood regulation. A polymorphism C218A in intron 7 of the tryptophan hydroxylase (TPH) gene has been hypothesized in relation to smoking predisposition. METHODS: We examined the association on two Japanese populations: one was from the first-visit outpatients of Aichi Cancer Center Hospital during 3-month period between April and June, 2001 (N=591), and the second was from the examinees who attended a health checkup program supported by the Nagoya municipal government in 2000 (N=446). Written documents on informed consent were obtained and lifestyle questionnaires were recorded. TPH C218A genotypes were determined by the polymerase chain reaction with confronting two-pair primers (PCR-CTPP) method. RESULTS: The frequencies of the C- and A-allele were 52% and 48%, respectively, which was in Hardy-Weinberg equilibrium. As for current smoking status, no associations were statistically observed. It was, however, indicated that smokers with A/A genotype started smoking earlier in their life. Among male health examinees, mean ages at starting smoking were 18.7 (A/A), 19.9 (C/A), and 22.4 years (C/C), (P<0.01). Also, on the Aichi Cancer Center Hospital subjects aged 60 and older, mean ages were 19.0 (A/A), 20.2 (C/A), and 20.3 years (C/C) for males and 22.3 (A/A), 31.0 (C/A), and 33.0 years (C/C) for females (P<0.05). CONCLUSIONS: The present study demonstrated that the TPH C218A polymorphism in intron 7 had no association with current smoking status in Japanese population. The hypothesis of early smoking initiation of A/A genotype was partially in agreement.     

SH2B接头蛋白1基因多态性及生活行为方式与儿童肥胖的关系

  目的  研究中国儿童人群中SH2B接头蛋白1基因(SH2B adaptor protein 1 gene, SH2B1)rs7498665多态性与肥胖及相关表型的关联, 为探讨生活方式对该多态性与肥胖关系的影响提供依据。  方法  选取北京市3 305名7~18岁儿童青少年进行身体测量和生活方式问卷调查。利用基质支持的激光释放/电离飞行时间质谱分析法对rs7498665多态性进行分型。采用多元Logistic回归和线性回归方法分析全部人群及不同饮食、运动水平下该基因多态性与肥胖及相关表型的相关性。  结果  在非健康膳食摄入、不是每天吃早餐、经常摄入含糖饮料、不是每天进行中高强度体育锻炼情况下, rs7498665多态性G等位基因与肥胖存在相关性, 肥胖风险分别升高37%, 101%, 45%和64%(P值均 < 0.05)。对不同生活方式进行综合评价, rs7498665多态性只在非健康生活方式组的人群中与肥胖发生有关(OR=1.63, 95%CI=1.23~2.17, P < 0.01)。分析肥胖相关表型发现相同趋势的结果, 该位点与综合生活方式存在交互作用(P_{基因×生活方式} < 0.05)。  结论  SH2B1基因rs7498665多态性与肥胖易感的非健康生活方式对儿童肥胖及相关表型存在相互作用。     

A genome‐wide linkage and association analysis of imputed insertions and deletions with cardiometabolic phenotypes in Mexican Americans: The Insulin Resistance Atherosclerosis Family Study

Insertions and deletions (INDELs) represent a significant fraction of interindividual variation in the human genome yet their contribution to phenotypes is poorly understood. To confirm the quality of imputed INDELs and investigate their roles in mediating cardiometabolic phenotypes, genome‐wide association and linkage analyses were performed for 15 phenotypes with 1,273,952 imputed INDELs in 1,024 Mexican‐origin Americans. Imputation quality was validated using whole exome sequencing with an average kappa of 0.93 in common INDELs (minor allele frequencies [MAFs] ≥ 5%). Association analysis revealed one genome‐wide significant association signal for the cholesterylester transfer protein gene (CETP ) with high‐density lipoprotein levels (rs36229491, P = 3.06 × 10^?12); linkage analysis identified two peaks with logarithm of the odds (LOD) > 5 (rs60560566, LOD = 5.36 with insulin sensitivity (S _I) and rs5825825, LOD = 5.11 with adiponectin levels). Suggestive overlapping signals between linkage and association were observed: rs59849892 in the WSC domain containing 2 gene (WSCD2 ) was associated and nominally linked with S _I (P = 1.17 × 10^?7, LOD = 1.99). This gene has been implicated in glucose metabolism in human islet cell expression studies. In addition, rs201606363 was linked and nominally associated with low‐density lipoprotein (P = 4.73 × 10^?4, LOD = 3.67), apolipoprotein B (P = 1.39 × 10^?3, LOD = 4.64), and total cholesterol (P = 1.35 × 10^?2, LOD = 3.80) levels. rs201606363 is an intronic variant of the UBE2F‐SCLY (where UBE2F is ubiquitin‐conjugating enzyme E2F and SCLY is selenocysteine lyase) fusion gene that may regulate cholesterol through selenium metabolism. In conclusion, these results confirm the feasibility of imputing INDELs from array‐based single nucleotide polymorphism (SNP) genotypes. Analysis of these variants using association and linkage replicated previously identified SNP signals and identified multiple novel INDEL signals. These results support the inclusion of INDELs into genetic studies to more fully interrogate the spectrum of genetic variation.