Cystatin C 基因 5'端-157G/C 突变与阿尔茨海默病的相关性研究

目的 探讨CystatinC基因5’端-157G／C突变与中国昆明地区汉族人阿尔茨海默病是否存在关联。方法 运用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析方法在134例无亲缘关系之中国昆明汉族人（正常对照组73例，阿尔茨海默病患者61例）中对CystatinC基因变异进行检测。同时检测两组人群血浆CystatinC之浓度。结果 在阿尔茨海默病患者中GG，GC和CC基因型频率分别为16．39％，50．82％和32．79％；正常对照组中分别为26．03％，41．10％和32．87％。G等位基因频率在阿尔茨海默病组中和正常对照组中分别为41．80％和46．58％。基因型频率和等住基因频率在阿尔茨海默病患者与对照组之间无统计学差异。两组人群血浆CystatinC浓度也无统计学差异。结论 在中国昆明汉族人群中存在Cystatin C基因5’端-157G／C变异的多态性，但可能对阿尔茨海默病的发生不起作用。     

脂联素基因启动子区-11377C／G单核苷酸多态性与中国北方汉族人2型糖尿病的关系

目的:分析脂联素基因启动子区-11377C/G(SNPs-11377C/G)单核苷酸多态性与中国北方汉族人2型糖尿病的关系。方法:选择2004/2005北京市和黑龙江哈尔滨地区的2型糖尿病流行病学调查资料中有糖尿病家族史,且相互间无亲缘关系的2型糖尿病患者348例,同时选择非糖尿病健康对照378例。所有研究对象均为汉族人,均签署了知情同意书。用聚合酶链反应-限制性片段长度多态方法鉴定脂联素基因启动子区SNPs-11377C/G的单核苷酸多态性。结果:726例研究对象均进入结果分析。①2型糖尿病组中CC,CG,GG基因型分别为171例(49.1%),151例(43.4%),26例(7.5%),正常对照组中CC,CG,GG基因型分别为180例(47.6%),173例(45.8%),25例(6.6%)。SNPs-11377C/G的基因型频率和等位基因频率在2型糖尿病组和正常对照组中的分布差异无显著性(P>0.05)。②SNPs-11377C/G的基因型频率和等位基因频率的分布性别差异也无显著性(P>0.05)。③SNPs-11377C/G不同基因型组中肥胖指标(体质量指数、腰围和腰臀比)的特征差异也无显著性(P>0.05)。结论:脂联素基因启动子区-11377C/G(rs266729)单核苷酸多态性与中国北方汉族人2型糖尿病无明显相关性。     

半胱氨酸蛋白酶抑制剂C基因G 73A位点的多态性与急性心肌梗死关系的探讨

目的探讨半胱氨酸蛋白酶抑制剂C（Cys C）基因外显子＋73G/A（简称G73A）位点变异与急性心肌梗死（AMI）的关系;同时观察池州地区汉族AMI患者血浆Cys C浓度的变化。方法采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）法分析112例AMI患者和110名健康对照者全血DNA中Cys C基因G73A位点变异的多态性分布情况,同时检测AMI组和对照组血浆Cys C浓度。结果AMI患者血浆Cys C浓度明显低于对照组（P〈0.05）。在AMI患者组中,G73A位点GG/GA/AA基因型频率分别为64.3%、28.6%和7.1%,G等位基因频率为78.6%;对照组G73A位点GG/GA/AA基因型频率分别为67.3%、28.3%和4.5%,G等位基因频率为81.4%,2组比较差异无统计学意义（P〉0.05）。结论Cys C水平的降低可能是AMI发病的危险因素之一;池州地区汉族AMI患者和正常人群中存在Cys C基因G73A位点变异的多态性,这个位点发生变异可能对AMI疾病的的发生不起主要作用。     

血管紧张素原基因5’端启动子区A-20C和A-6G单核苷酸多态性与蒙古族人群原发性高血压的相关性

目的:分析血管紧张素原基因启动子区A-20C和A-6G单核苷酸多态性与蒙古族人群原发性高血压的相关性。方法:实验于2005-08/2006-01在北京华大实验室完成。选取对象均为生活在内蒙古乌拉特后旗的蒙古族牧民,三代血亲内无其他民族。采用基因测序技术对内蒙古蒙古族人群中107例原发性高血压患者和108例正常对照者进行A-20C和A-6G基因分型,观察高血压组和正常对照组不同基因型的分布和等位基因频率的差异。结果:①两组受试者在性别、年龄及吸烟、饮酒、体质量指数和临床化验检查指标有较好的匹配(P均>0.05)。②两组血管紧张素原基因A-20C位点AA,AC,CC基因型频率比较差异无显著性意义(高血压组分别为0.51,0.29,0.20;正常对照组分别为0.49,0.28,0.23,χ2=0.395,P=0.529)。A,C等位基因频率比较差异无显著性意义(高血压组分别为0.65,0.35;正常对照组分别为0.63,0.37,χ2=0.015,P=0.904)。③两组血管紧张素原基因A-6G位点AA,AG,GG基因型频率比较差异无显著性意义(高血压组分别为0.50,0.33,0.17;正常对照组分别为0.55,0.34,0.11,χ2=1.924,P=0.165)。A,G等位基因频率比较差异无显著性意义(高血压组分别为0.66,0.34;正常对照组分别为0.72,0.28,χ2=1.728,P=0.189)。④高血压组协同存在血管紧张素原基因A-20C基因型CC时,血管紧张素原基因A-6G基因型GG频率稍高于正常对照组,但差异无显著性意义(χ2=2.395,P=0.122,OR=7.52,95%CI0.014～1.250),高血压组G等位基因明显高于正常对照组(分别为0.37,0.22,χ2=4.658,P=0.034),携带该等位基因的蒙古族人群发生原发性高血压的相对危险度升高(OR=2.80,95%CI1.087～7.271)。结论:血管紧张素原基因A-20C和A-6G单核苷酸多态性与蒙古族人群原发性高血压相关,并可能具有协同作用。     

抵抗素基因外显子及部分内含子单核苷酸多态性与2型糖尿病的关联研究

目的 探讨抵抗素基因四个外显子和部分内合子是否存在单核苷酸多态性，及其与2型糖尿病的相关性。方法 选取中国安徽地区汉族人2型糖尿病患者307例。正常对照102例。采用聚合酶链反应-单链构象多态方法，对抵抗素基因的四个外显子及部分内含子进行筛查，并做进一步基因分析。结果 在安徽地区汉族人中存在抵抗素基因的单核苷酸多态性，分别为-157G／A、＋115C／G、＋877G／C；2型糖尿病组与对照组基因型及等位基因频率差异均无显著性（均为P〉0．05）。结论 在安徽地区汉族人中，抵抗素基因存在单核苷酸多态性，但与2型糖尿病无相关性。     

IL-6基因572C/G多态性与江苏宿迁地区汉族人群冠心病的关系

目的分析江苏宿迁地区汉族人群IL-6基因-572C/G多态性与冠心病(CHD)的关系。方法采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术检测197例CHD患者及202例健康对照者IL-6基因-572C/G多态性,并进行HardyWeinberg平衡检验,选取部分DNA进行测序,以验证其基因型;用AU5400全自动生化分析仪测定其血糖和血脂水平。结果IL-6-572C/G基因频率在CHD组和健康对照组中均具有群体代表性(P0.05);健康对照组和CHD组CC、CG、GG基因型分布分别为53.5%、41.1%、5.4%和36.6%、49.7%、13.7%,C,G等位基因频率则分别为74.0%、26.0%和61.4%,38.6%。与健康对照组比较,CHD组IL-6-572C/G的CG+GG基因型频率显著升高(χ~2=11.53,P=0.007);危险因素分析结果显示,IL-6-572G等位基因增加了CHD患病风险(OR=1.79,95%CI:1.32~2.42,P=0.000)。在CHD组中,血糖血脂水平在IL-6-572CC、CG和GG 3种基因型间的差异无统计学意义(P0.05)。早发冠心病与健康对照组比较结果显示CG+GG基因型频率显著升高(χ~2=5.52,P=0.019),且G等位基因频率显著升高(χ~2=6.01,P=0.014);但早发冠心病与晚发冠心病比较,所有基因型差异均无统计学意义(P0.05)。结论 IL-6-572G等位基因与江苏宿迁地区汉族人群CHD的发病密切相关,与早发CHD易感性亦显著相关。     

白细胞介素6基因-174G/C和-634C/G多态性与冠心病的相关性研究

目的探讨白细胞介素6(interleukin6,IL6)基因启动子上游174G/C和634C/G基因多态性,在冠心病患者和正常人群中的分布及与冠心病的相关性。方法应用聚合酶链反应限制性片断长度多态性技术,对汉族199例冠心病患者及189名正常人群,白细胞介素6基因174G/C、634C/G位点进行研究,同时结合血脂、脂蛋白和载脂蛋白水平,探讨两者之间的关系。结果正常人群和冠心病患者的174G等位基因频率均为0.99。174C等位基因频率均为0.01。634C等位基因频率在正常人群和冠心病患者分别为0.82和0.76,G等位基因频率分别为0.18和0.24,两者差异有统计学意义(P<0.05)。冠心病患者634GG基因型频率(0.08)明显高于对照组(0.02)(P<0.05)。结论白细胞介素6基因174位点多态性与冠心病无关,而634位点多态性与冠心病有相关性。G等位基因可能是汉族人群冠心病的易感性标志。     

白细胞介素-18基因多态性与肺结核病易感性的关系

目的：通过病例-对照研究,探讨白细胞介素-18（IL-18）基因启动子区-607C/A、-137G/C位点单核苷酸多态性（SNP）与肺结核病的关系。方法：采用序列特异性引物PCR（PCR-SSP）及测序技术检测深圳地区汉族人群肺结核患者200例及健康对照者197例IL-18启动子区-607 C/A 、-137G/C位点多态性基因型。采用直接计数法计算各组基因型频率及等位基因频率,进行χ2 检验。以P值＜0.05为具有统计学意义。结果：肺结核患者IL-18启动子区-607位点A/A纯合子、A/C杂合子、C/C纯合子基因型频率分别为19.5%、55.0%、25.5% ;A、C等位基因频率分别为47.0%、53.0%。健康对照者A/A纯合子、A/C杂合子、C/C纯合子基因型频率分别为22.8%、46.7%、30.5%;A、C等位基因频率分别为46.2%、53.8%。两组人群-607位点基因型及等位基因分布无明显差异(P>0.05)。肺结核患者IL-18启动子区-137G/C位点C/C纯合子、C/G杂合子、G/G纯合子基因型频率分别为4.5%、18.5%、77.0%;C、G等位基因频率分别为13.8%、86.2%。健康对照者C/C纯合子、C/G杂合子、G/G纯合子基因型频率分别为5.6%、25.9%、68.5%;C、G等位基因频率分别为18.5%、81.5%。两组人群-137位点基因型分布无明显差异(P>0.05)。结论：IL-18启动子区-607、-137位点基因多态性与中国汉族人群肺结核病易感性无关。     

2型糖尿病患者FAT／CD36基因启动子区-3489C／T和密码子区478C／T多态性研究

目的探讨FAT／CD36脂肪酸转位酶基因启动子区-3489C／T和密码子区478C／T多态性与2型糖尿病（T2DM）的相关性。方法运用聚合酶链反应-限制性片段长度多态性技术对196例T2DM患者和120例正常对照者的-3489C／T与478C／T多态性进行检测，并比较各组间基因型频率和等位基因频率以及相关临床资料。结果（1）所有研究对象均无一例存在FAT／CD36基因启动子区478C→T突变，基因型均表现为478CC之纯合子，478CC和478TT等位基因频率分别为1和0。（2）T2DM组和正常对照组的-3489C／T多态性基因型和等位基因频率比较差异无统计学意义，P值分别为0．682和0．683。结论昆明地区的汉族人中FAT／CD36基因的启动子区一3489C／T和密码子区478位C／T多态性与昆明地区汉族人群2型糖尿病的发生无显著相关关系。     

骨保护素基因G1181C多态性在维持性血透患者人群中的分布

目的:探讨骨保护素(OPG)基因启动子区G1181C基因型和等位基因频率在维持性血液透析(MHD)患者人群中的分布差异。方法:采用MALDI-TOFMS技术检测110例长沙地区MHD患者和OPG基因G1181C多态性位点的基因型。结果:(1)湖南长沙地区汉族MHD人群OPG基因G1181C基因型频率分布符合Hardy-Weinberg遗传平衡定律;(2)G1181C基因多态性频率分布比较差异在不同性别、原发病患者中有统计学意义;(3)湖南长沙地区MHD患者OPG基因G1181C多态性位点GG基因型发生频率最高(53.5%),基因型GC频率次之(30.4%),CC基因型频率最低(16.1%),基因型和等位基因频率分布与欧洲人群有一定差异,与日本及上海地区人群差异无统计学意义。结论:湖南长沙地区MHD患者OPG基因G1181C多态性频率分布可能存在性别、原发病及种族特异性。     

Analysis of the C314T and A595G mutations in histamine N-methyltransferase gene in a Chinese population

BACKGROUND: Histamine N-methyltransferase (HNMT) plays an important role in the metabolism of histamine, a biogenic amine that has many physiologic and pathological roles in human tissues. A missense mutation C314T (Thr105Ile) in the HNMT gene has been identified to represent a common functional polymorphism in Caucasians, whereas an A595G (Ile199Val) variant has been reported in one HNMT cDNA from a Japanese subject. METHODS: By using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay, the point mutations C314T and A595G within HNMT were both detected in 352 unrelated Chinese Han subjects. RESULTS: None of the 352 subjects contained the A595G mutation, whereas 40 (11.6%) heterozygotes and 1 (0.3%) homozygote for the variant T314 allele were detected. The frequency of the variant T314 allele in this Chinese population was 0.060 (95% CI: 0.042-0.078), not different from Japanese but significantly lower than American Caucasians. CONCLUSIONS: The C314T mutation represents a common functional genetic polymorphism in the Chinese Han population with a variant T314 allele frequency similar to Japanese but lower than American Caucasians, whereas the A595G mutation does not appear to exist in this population.     

新疆汉族GGCX基因rs11676382位点多态性与心房颤动的相关性研究

目的研究汉族GGCX基因rs11676382位点多态性与心房颤动(AF)的相关性。方法以200例汉族未服用华法林的心房颤动患者作为研究组,200例健康汉族患者作为对照组,所有患者均采集外周血提取基因组DNA,采用聚合酶链反应,限制性片段长度多态性技术(PCRRFLP)检查患者GGCX基因rs11676382多态性的基因型和等位基因频率分布,观察GGCX基因rs11676382多态性与心房颤动的关系。结果GGCX基因rs11676382位点在入选人群中的基因型及等位基因分别为CC、CG和GG型,其基因型频率在心房颤动组和对照组分别依次为82.5%、16.5%、1.0%和85.0%、0.5%、14.5%,分布趋势相同,差异无统计学意义(P0.05);C和G等位基因频率在心房颤动组和对照组分别为99.0%,1.0%和99.5%,0.5%,C和G等位基因频率在两组间的差异无统计学意义(P0.05)。结论 GGCX基因rs11676382多态性与未服用华法林的心房颤动无相关性。     

MTHFR C677 T gene polymorphism in lymphoproliferative diseases

Methylenetetrahydrofolate reductase (MTHFR), a key enzyme in folate metabolism, has been implicated in cancer risk. In the present study we used a melting curve analysis to investigate the association of the common MTHFR C677 T polymorphism with lymphoproliferative diseases. Patients (n=117) were compared with age- and sex-matched control subjects (n=154). Our results indicate that the 677 T variant occurred less frequently in patients (26%) than in the control group (33.7%; P=0.05). Investigation of the variant allele (677 T) frequency in the subgroups with Hodgkin's lymphoma (HL) and B-cell neoplasms (BCNs) revealed that this difference was a result of the significantly lower distribution of the variant allele in patients with HL (20.5%; P=0.01). This was accompanied by a significantly higher frequency of the homozygote normal genotype (677CC) among the patients with HL. In patients with BCNs the distribution of the variant allele (30.3%) was comparable to that in the control group (P=0.47). However, the difference between HL (20.5%) and BCNs (30.3%) did not reach statistical significance (P=0.09). Our results suggest that the distribution of the C677 T polymorphism may vary among lymphoproliferative diseases.     

Interleukin-18 and IL18 -607A/C and -137G/C gene polymorphisms in patients with penicillin allergy

This study investigated the association between polymorphisms (-607A/C and -137G/C) in the promoter region of the IL18 gene (which encodes interleukin [IL]-18) and serum levels of IL-18, using standard genotyping techniques (sequence specific primer-polymerase chain reaction) and an enzyme-linked immunosorbent assay, respectively, in patients allergic to penicillin. A higher frequency of A alleles and the AA genotype was found at position -607A/C in patients allergic to penicillin than in control subjects. For the -137G/C position, the C allele was more frequent in patients allergic to penicillin than in control subjects. Haplotype analysis showed that the -607A/-137C haplotype was more frequent in patients allergic to penicillin than in control subjects. The patients had a significantly higher serum IL-18 level than the control subjects. In conclusion, IL18 -607A/C and -137G/C promoter polymorphisms are associated with susceptibility to penicillin allergy. In particular, the -137G/C position appears to play an important role in IL18 expression.     

内皮细胞蛋白C受体基因多态性与湖北省地区汉族人群脑梗塞的相关性研究

本研究旨在了解湖北省地区汉族人群内皮细胞蛋白C受体（EPCR）A6936G变异的分布频率,探讨其与脑梗塞的关系。应用PCR-RFLP方法在湖北省地区汉族人群中检测380名脑梗塞患者和380名健康体检者的EPCRA6936G变异。结果表明,脑梗塞患者A／A、A／G和G／G基因型的频率分别为77．1％、22．1％和0．8％,而健康体检者A／A和A／G基因型的频率分别为88．2％和11．8％,未发现G／G基因型。综上所述作出下述结论：湖北省地区汉族人群中存在EPCR A6936G变异,它与脑梗塞患者血栓形成的风险增高有关。     

Association of CTLA-4 gene A/G polymorphism in Japanese type 1 diabetic patients with younger age of onset and autoimmune thyroid disease

OBJECTIVE: We studied the association between type 1 diabetes with autoimmune thyroid disease (AITD) and A/G allele polymorphism in exon 1 of the CTLA-4 gene in a Japanese population. RESEARCH DESIGN AND METHODS: We studied 74 Japanese type 1 diabetic patients with or without AITD and 107 normal subjects to identify the association between CTLA-4 polymorphism and type 1 diabetes using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The frequency of the CTLA-4 G allele differed significantly between the type 1 diabetic patients (61%) and the normal control subjects (48%) (P = 0.016). The difference in the CTLA-4 G allele became greater between patients with a younger age of onset of type 1 diabetes (age at onset <30 years) and the normal control subjects (64% and 48%, respectively). However, the frequency of the CTLA-4 G allele did not differ between type 1 diabetic patients with younger and older age of onset (64% vs. 57%). The G allele frequencies in the patients with younger-onset type 1 diabetes and AITD increased more than in the control patients (P = 0.025). These differences reflected a significant increase in the frequency of G/G genotype--that is, 54% in those with younger-onset type 1 diabetes and AITD, 39% in those without AITD, and 28% in control subjects. CONCLUSIONS: An association was detected between the CTLA-4 gene polymorphism and younger-onset type 1 diabetes with AITD. The G variant was suggested to be genetically linked to AITD-associated type 1 diabetes of younger onset in this apanese population. The defect in these patients presumably lies in a T-cell-mediated autoimmune mechanism.     

解偶联蛋白2启动子-866G／A多态性与中国北方儿童肥胖病相关性研究

目的：研究解偶联蛋白2（UCP2）基因启动子-866G/A单核苷酸多态性与中国北方儿童肥胖病遗传发病机制的相关性。方法病例组选取2010年1～9月于北京儿童医院内分泌科就诊且无血缘关系的儿童肥胖病患者220例。对照组选自无血缘关系的成年健康献血员220例。用血液基因组DNA提取试剂盒提取外周血基因组DNA,UCP2基因启动子-866G/A单核苷酸多态性分析采用PCR-RFLP法,并选取部分标本进行测序分析。结果（1）UCP2基因启动子-866A等位基因在中国肥胖病儿童中的频率与正常对照组相近,无统计学差异（44．8％ vs．46．4％,χ2＝0.224,P＝0.685）。（2）GG、GA和AA基因型在患者频率分布为34．5％、41．4％及24．1％;在对照组中的分布为27．3％、52．7％及20.0％,三者在患者与对照中的频率分布无显著性差异（ P＞0.05）。包含等位基因A的基因型AA和GA基因型频率之和在对照组中的频率增加,但无统计学差异（65．5％vs．72.7％,P＝0.122）。按性别进行分层分析,肥胖病男童与对照组的基因型频率分布尚无显著性差异（ P＝0.05）,在女童中亦无显著性差异（ P＝0.512）。结论 UCP2基因启动子-866 G/A单核苷酸多态性与中国儿童肥胖病遗传发病机制未见显著相关性。 UCP2基因启动子-866 G/A多态性与肥胖病的遗传发病机制的相关性存在一定的人种差异。     

Association between the CYP2C9 polymorphism and the drug metabolism phenotype.

CYP2C9, an isoform of the cytochrome P450 enzyme, is involved in the metabolism of most of the drugs of choice for the treatment of thromboembolic disorders. Functional polymorphism is associated with two variant alleles (alleles *2 and *3) encoding CYP2C9 enzymes with a potentially different catalytic activity. The aim of the study was to determine the frequency of the CYP2C9 polymorphism in a representative sample of the Croatian population (n = 177) and to assess the association between the CYP2C9 polymorphism and the warfarin dose in patients with thromboembolism (n = 181). The CYP2C9 genotype was determined by polymerase chain reaction-restriction fragment length poymorphism (PCR-RFLP). According to the CYP2C9 genotype distribution, 31.2% of the healthy subjects were identified with a heterozygous or homozygous CYP2C9 variant genotype. The frequency of 2C9*2 and 2C9*3 alleles was 12.4% and 3.7%, respectively. There was no gender-related genotype or allele difference. In thromboembolism patients, the frequency of CYP2C9 alleles *2 and *3 was 17.4% and 6.6%, respectively, and did not differ significantly from the control group. Almost half (42.5%) of the patients carried at least one variant CYP2C9 genotype. The allele difference between patient subgroups receiving warfarin doses lower and higher than the optimal warfarin dose (4.1 mg/day) was significant (p = 0.027), especially for allele 2C9*3 (p = 0.019; OR 3.250, 95%, CI 1.263-8.413). Comparison of the warfarin dose between patients with different genotypes yielded a significant dose difference between the patients with wild-type genotype and those with variant genotypes (Kruskall-Wallis, chi2 = 9.745, p = 0.008). The results of the association of each of five genotype combinations with the warfarin maintenance dose revealed it to be significantly related to the genotype (Kruskall-Wallis, chi2 = 12.854, p = 0.025). Expressed as percentage of the mean dose in patients with wild-type alleles, the mean warfarin maintenance dose was 92% in 2C9*2 heterozygotes, 74% in 2C*3 heterozygotes, 61% in 2C9*2 homozygotes, 34% in 2C9*3 homozygotes and 63% in compound heterozygotes for 2C9*2 and 2C9*3. Although the mean maintenance dose in homozygous *2/*2 and compound *2/*3 genotype patients was markedly lower (mean 2.66 mg and 2.75 mg, respectively, vs. 4.37 mg), statistical analysis yielded no significance because of the small number of patients carrying these genotypes. A significantly lower maintenance dose was observed in the subgroup of heterozygous *1/*3 genotype patients (p = 0.022). These preliminary results suggest a significant association of the CYP2C9 polymorphism with the warfarin dose and underline the importance of pre-therapeutic genotyping to identify the subjects likely to develop undesirable drug effects.