广西瑶族与汉族人群TGF-β1基因启动子-509 C/T多态性的研究

目的研究TGF-β1(转化生长因子-β1)基因多态性在广西瑶族与汉族人群中的分布.方法应用聚合酶链反应-限制性片段长度多态性技术检测150名瑶族人和190名汉族人的TGF-β1基因多态性,比较两组人群TGF-β1基因型和等位基因的分布频率.结果在瑶族人中CC基因型占46.0%、CT基因型占43.3%、TT基因型占10.7%;在汉族人中CC基因型占30.0%、CT基因型占51.1%、TT基因型占19.9%.两组人群TGF-β1基因型的分布频率差异有显著性(P＜0.05).结论瑶族与汉族人群TGF-β1基因多态性分布频率差异有显著性.     

西藏藏族人群白细胞介素1受体拮抗剂基因多态性

目的:研究白细胞介素-1受体拮抗剂(IL-1Ra)在西藏藏族健康人群中的分布特点,并与其他不同人群进行比较.方法:采用PCR的方法,对125名西藏拉萨市藏族人群IL-1Ra基因的可变数目串联重复序列多态性进行检测,计算其基因型频率和等位基因频率,并结合文献与其他不同人群进行比较分析.结果:西藏藏族人群IL-1Ra位点基因型以A1/A1纯合子型最为多见(频率为90.40%),A1/A2杂合子型次之(频率为9.60%),A2/A2纯合子型未检测到;其等位基因分布也是以A1等位基因最为多见 (频率为95.20%),其次为A2等位基因(频率为4.80%).西藏藏族人群的等位基因频率分布与美国人、德国人、非洲白人差异较大,具有统计学意义.而与亚洲人群包括日本人和中国汉族差异较小.结论:西藏拉萨市藏族人群中IL-1Ra位点以A1等位基因为主,其多态性分布与其他人群之间存在明显的差异,为进一步研究IL-1Ra基因多态性与疾病的关系奠定了基础.     

中国北方汉族人群β2肾上腺素能受体基因多态性研究

目的 :探讨 β2 AR16、2 7和 16 4位点基因多态性在中国北方汉族人群中的分布 ;方法 :采用等位基因特异性PCR方法 ,对 β2 AR基因多态性进行分析检测 ;结果 :中国汉族人群 β2 AR16位点基因多态性分布频率 :Arg/Arg基因型占 13% ,Arg/G1y基因型占 76 % ,G1y/G1y基因型占 11% ;β2 AR基因 2 7位点多态性分布频率 :G1n/G1n基因型占 36 % ,G1n/G1u基因型占5 5 % ,G1u/G1u基因型占 9% ;β2 AR基因 16 4位点多态性分布 ,Thr/Thr基因型占 30 % ,Thr/Ile基因型占 5 3% ,Ile/Ile基因型占17%。结论 :我国北方汉族人群存在 β2 AR基因多态性 ,其分布频率与英美高加索人群有一定差异     

广西壮族与汉族人群的转化生长因子-β1基因多态性

目的研究转化生长因子-β1(TGF-β1)基因-509C/T位点多态性在广西壮族与汉族人群中的分布.方法应用聚合酶链反应-限制性片段长度多态性技术(PCR-RFLP)检测180名壮族人和170名汉族人的TGF-β1基因-509C/T位点多态性,比较两组人群TGF-β1基因型和等位基因的分布频率.结果在壮族人中CC基因型占41.1%、CT基因型占46.1%、TT基因型占12.8%;在汉族人中CC基因型占28.9%、CT基因型占52.9%、TT基因型占18.2%.两组人群TGF-β1基因型的分布频率差异有显著性.结论壮族与汉族人群TGF-β1基因多态性分布频率差异有显著性.     

贵州三个少数民族谷胱甘肽S-转移酶M1、T1和P1基因多态性

目的研究贵州省从江县侗族、威宁县彝族、荔波县瑶族的谷胱甘肽S-转移酶基因(GSTs)多态性。方法在隔离自然人群(从江县侗族108人、威宁县彝族104人、荔波县瑶族109人)中,采用多重等位基因特异聚合酶链反应方法分析GSTM1和GSTT1基因多态性,采用聚合酶链反应及限制性片段长度多态性方法分析GSTP11578(A→G)基因多态性。结果贵州省从江县侗族、威宁县彝族、荔波县瑶族的GSTM1和GSTT1纯合缺失基因型频率分别为59.6%～71.2%、39.4%～72.5%。其GSTP11578(A→G)基因型频率分别是:AA为63.3%～75%、AG为23.2%～35.8%、GG为0～1.9%。等位基因频率:A为81.2%～86.6%,G为13.4%～18.8%。结论GSTT1基因型频率在贵州从江侗族、威宁彝族、荔波瑶族中存在差异,其分布特征可能与人群中不同种族以及同一种族不同民族相关。     

中国湖北地区汉族人群L-选择素基因P213S多态性研究

目的:了解中国湖北地区汉族人群L-选择素基因第六外显子P213S多态性分布,并与其它地区的分布进行比较。方法:应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,检测206名健康者L-选择素基因P213S多态性基因型和等位基因频率分布。结果:L-选择素各基因型频率分别为PP型(45.63%)、PS型(49.03%)和SS型(5.34%)。P、S等位基因频率分别为70.15%和29.85%,这种基因多态性分布无性别差异(P>0.05)。湖北地区汉族人群L-选择素基因型和等位基因频率分布与英国及日本人有显著性差异(P<0.05)。结论:湖北地区汉族人群中存在L-选择素基因多态性,与其它地区分布比较有明显的差异。     

湖南汉族人群CX3CR1基因多态性分布

目的探讨趋化因子受体CX3CR1基因多态性在湖南汉族健康人群中的分布及其与国内外不同种族之间的差异。方法采用PCR-RFLP技术对150名湖南汉族健康体检者进行CX3CR1基因多态性检测,计算其基因型和等位基因频率,并与国内外多个民族CX3CR1基因多态性分布进行比较。结果湖南汉族人群V249I基因位点有VV和VI两种基因型,以VV基因型为主,没有II基因型,其中VV基因型频率为88%,VI基因型频率为12%,V和I等位基因频率分别为94%和6%;T280M基因位点有TT和TM两种基因型,以TT基因型为主,没有II基因型,其中TT基因型频率分别为95.3%,TM基因型频率为4.7%,T和M等位基因频率分别为97.7%和2.3%。结论湖南汉族CX3CR1基因V249I以VV基因型为主,缺少II和MM基因型,湖南汉族、新疆汉族、景族和傣族都缺少II基因型,T280M以TT基因型为主,缺少MM基因型,湖南汉族CX3CR1基因多态性分布与维吾尔族人群和欧美人群存在较大差异,与国内景族、傣族、新疆汉族和日本人群相似。     

广东汉族人群MICA和MICB微卫星多态性分布

目的　调查广东地区汉族人群 MICA基因第 5外显子和 MICB基因第 1内含子微卫星多态性分布。方法　应用聚合酶链反应和荧光 ( 6 - FAM)自动化检测技术 ,对广东地区共 10 6名无亲缘关系样本进行 MICA和 MICB微卫星基因分型 ,并计算这两个微卫星的基因频率、基因型频率、个体鉴别力、期望杂合性、多态性信息含量和非父排除率。结果　MICA和 MICB微卫星基因型分布符合 Hardy- Weinberg平衡。MICA A5基因频率最高为 0 .2 877,A4基因频率则最低为 0 .132 1;A5 - 5 .1( 14 .15 % )和 A5 - 5 ( 10 .38% )基因型分布频率较高。 MICB CA14等位基因频率最高为 0 .32 5 5 ,CA19、CA2 8等位基因频率最低为0 .0 0 4 7,未检出 CA2 7。 CA14 - CA14 ( 14 .15 % )基因型分布频率较高。结论　 MICA基因第 5外显子和MICB基因第 1内含子微卫星适合作为中国人群的遗传标志 ,用于人类学、遗传疾病基因连锁分析、法医学亲子鉴定和个体识别等研究领域     

湖南汉族人群CX3CRl基因多态性分布

目的 探讨趋化因子受体CX3CR1基因多态性在湖南汉族健康人群中的分布及其与国内外不同种族之间的差异.方法 采用PCR-RFLP技术对150名湖南汉族健康体检者进行CX3CR1基因多态性检测,计算其基因型和等位基因频率,并与国内外多个民族CX3CR1基因多态性分布进行比较.结果 湖南汉族人群V249I基因位点有VV和Ⅵ两种基因型,以VV基因型为主,没有II基因型,其中VV基因型频率为88%,VI基因型频率为12%,V和I等位基因频率分别为94%和6%;T280M基因位点有TT和TM两种基因型,以TT基因型为主,没有Ⅱ基因型,其中TT基因型频率分别为95.3%,TM基因型频率为4.7%,T和M等位基因频率分别为97.7%和2.3%.结论 湖南汉族CX3CRl基因V249I以VV基因型为主,缺少Ⅱ和MM基因型,湖南汉族、新疆汉族、景族和傣族都缺少Ⅱ基因型,T280M以TT基因型为主,缺少MM基因型,湖南汉族CX3CR1基因多态性分布与维吾尔族人群和欧美人群存在较大差异,与国内景族、傣族、新疆汉族和日本人群相似.     

汉族儿童Ⅱ相药物代谢酶基因GSTM1和GSTT1的多态性分布

目的了解谷胱甘肽-S-转移酶M1（GSTM1）和T1（GSTT1）基因多态性在中国汉族儿童中的分布特点,为临床针对不同基因型个体化药物治疗提供理论基础。方法选择首都医科大学附属北京儿童医院健康查体汉族儿童的血样,提取DNA。应用PCR法检测GSTM1和GSTT1基因型,并判断代谢表型。检索PubM ed等数据库,获得亚洲人群、黑种人和高加索人群GSTM1和GSTT1基因多态性分布的数据,与本研究分析人群数据进行比较,分析基因多态性的种族差异。结果 786份研究样本纳入分析。①中国汉族分析人群GSTM1和GSTT1完全缺失基因型/慢代谢型（＊0/＊0）的频率分别为59.3%（466/786例）和58.4%（459/786例）;单拷贝缺失基因型/中间代谢型（＊1/＊0）的频率分别为34.0%（267/786例）和35.1%（276/786例）;未缺失基因型/快代谢型（＊1/＊1）的频率分别为6.7%（53/786例）和6.5%（51/786例）。②GSTM1和GSTT1基因多态性分布互相独立,无明显关联。③GSTM1和GSTT1基因多态性无显著性别差异。④本研究汉族分析人群GSTM1和GSTT1基因多态性分布与亚洲人群较为接近,与黑种人和高加索人群有显著差异。结论 GSTM1和GSTT1基因在中国汉族儿童中以完全缺失基因型/慢代谢型（＊0/＊0）为主,具有种族特异性,为不同基因型个体制定合适的用药方案提供了参考依据。     

Research on the association between glutathione S-transferase P1 genic polymorphism and heart rate and blood pressure

Oxidative stress may reduce cardiovascular function. Glutathione Stransferases(GSTs) play an important role in cell defending against oxidative stress. Glutathione S-transferase P1 (GSTP1) gene is one of the most intensively investigated glutathione S-transferase genes in epidemiologic studies. The GSTP1 gene displays a polymorphism at codon 105 (Ile105 Val), which results in an enzyme with altered substrate affinity. To date, there have been few studies evaluating whether Ilel05Val polymorphism of GSTP1 gene has an effect on cardiovascular function in the broad masses of people. In this study, we investigated the relationship between Ile105 Val polymorphism of GSTP1 gene and heart rate and blood pressure in 197 unrelated adult males of Han nationality. It was found that there were two types of the GSTP1 genotypes, Ile105/Ile105 and Ile105/Val105, but genotype Val105/Val105 was not found, and the frequencies of IleIes/Ileos and Ile105/Val105 genotypes were 78% and 22% respectively. Comparison with individuals with lie105/Val105 genotype showed that those with Ile105/Ile105 genotype had higher rest heart rate and maximal heart rate mean values. However, whether for rest heart rate and maximal heart rate or for heart rate reserve, no significant differences were found between the two genotype groups (P>0.05). Compared with individuals with Ile105/Val105 genotype, those with Iler105/Ile105 genotype had higher systolic blood pressure and pulse pressure mean values and lower diastolic blood pressure mean value. However, for systolic blood pressure, diastolic blood pressure and pulse pressure, no significant differences were found between the two genotype groups (P>0.05). The results suggested that Ile105 Val polymorphism of GSTP1 gene may not be associated with heart rate and blood pressure in the broad masses of people.     

GSTM1, GSTT1 and GSTP1 polymorphisms in the Korean population

The isoenzymes of the glutathione s transferase (GST) family play a vital role in phase II of biotransformation of many substances. Using a multiplex polymerase chain reaction and a direct sequencing analysis, the frequencies of GSTM1, GSTT1, and GSTP1 polymorphisms were evaluated in 1,051 Korean male subjects. We found that 53.8% of the individuals had the GSTM1 null genotype and 54.3% had the GSTT 1 null genotype. The genotypic distribution of GSTP1 was Ile105/Ile105 in 68.4%, Ile105/Val105 in 29.1% and Val105/Va105 in 2.5%. The most frequently observed combination of GSTM1, GSTP1 and GSTT1 genotypes was Null type/Ile105/Ile105/Null type, while the combination of Non-null type/Val105/Val105/Non-Null type was not observed. We found that the genotype distributions of three GST isoenzymes in the Koreans are similar to those reported in Asians and previously reported Koreans. We believe our results, which are represented by a large population, are reliable estimates of the frequencies of the polymorphic GST alleles in the Koreans and will help future researches on GST polymorphisms.     

Combined effects of glutathione S-transferase polymorphisms and thyroid cancer risk

Since exposure to ionizing radiation, a risk factor for thyroid cancer, may produce genotoxins potentially eliminated by glutathione-S-transferases, we conducted a case control study to evaluate the role of the GSTM1- and GSTT1-null genotypes and GSTP1 polymorphisms in thyroid cancer. The frequency of GSTP1 Ile/Ile, GSTM1-, and GSTT1-null genotypes was increased in cancer patients when compared with control population. Considering the genotypes over-represented in thyroid cancer patients as potential risk genotypes, we carried out an odds ratio (OR) analysis considering the presence of none, one, two, or three risk genotypes. The results obtained showed that the presence of three potentially risk alleles (GSTM1 null, GSTT1 null, and GSTP1 Ile/Ile) lead to a significant OR increase for all the cases, irrespective of the type of tumor (OR=2.91), for papillary (OR=3.64) but not for follicular tumors. The presence of GSTP1 Ile/Ile leads to a significant later age of tumor onset when compared with GSTP1 Ile/Val and Val/Val (P<0.05), suggesting a possible association between GSTP1 Ile/Ile and the age of disease manifestation. These results suggest that combined GST polymorphisms lead to a moderate increased risk for thyroid cancer, especially for the papillary type, and GSTP1 polymorphisms might modulate the age of onset of the disease.     

Polymorphisms of Glutathione S-Transferase Mu 1 (GSTM1), Theta 1 (GSTT1), and Pi 1 (GSTP1) Genes and Epithelial Ovarian Cancer Risk

Background: Exposure of ovarian cells to estrogen, which is detoxified by glutathione S-transferases (GSTs), has been associated with epithelial ovarian cancer (EOC) development. Objectives: We tested in this study whether the GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms alter the risk of EOC. Materials and methods: Genomic DNA from 132 EOC patients and 132 controls was analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. The differences between groups were analyzed by χ² or Fisher’s exact test. Results: The frequencies of GSTP1 Ile/Ile (57.6% versus 45.5%, P = 0.03), GSTM1 null plus GSTP1 Ile/Ile (43.5% versus 25.8%; P = 0.03) and GSTM1 null plus GSTT1 null plus GSTP1 Ile/Ile (30.3% versus 7.7%; P = 0.007) genotypes were higher in patients than in controls. Individuals with the respective genotypes had a 1.80 (95% CI: 1.06–3.06), 2.38 (95% CI: 1.08–5.24) and 11.28 (95%CI: 1.95–65.30)-fold increased risks of EOC than those with the remaining genotypes. Conclusions: Our data present preliminary evidence that GSTM1, GSTT1 and GSTP1 polymorphisms, particularly in combination, constitute important inherited EOC determinants in individuals from Southeastern Brazil.     

韩国人CYP450 1A1、CYP450 2E1和GSTM1、GSTT1、GSTP1基因座遗传多态性分析

目的 调查代谢相关的CYP4501A1、CYP4502E1和GSTM1、GSIT1、GSTP1基因座在韩国人群中的遗传多态性分布状况。方法 采用多重聚合酶链式反应、聚合酶链式反应-限制性片段长度多态性技术，分析300名韩国健康大学生的CYP1A1基因3′端限制性内切酶Msp Ⅰ位点、CYP2E1基因5′端转录调节区Pst Ⅰ位点和GSTM1、GSTT1缺失与存在、GSTP1基因第5外显子BsmA Ⅰ位点的基因型，计算基因型和基因频率。结果 CYP1A1基因型频率为ml／ml型39．7％、ml／m2型49．7％、m2／m2型10．7％，基因频率为ml 0．645、m2 0．355。CYP2E1基因型频率为cl／cl型66．7％、cl／c2型30％、c2／c2型3．3％，基因频率为C1 0．818、C2 0．182。GSTM1基因缺失型频率为53．3％。GSTT1基因缺失型频率为54．7％。GSTP1基因型频率为Ile／Ile型62％、Ile／Val型34．3％、VaL／Val型3．7％，基因频率为Ile 0．792、Val 0．208。基因分布符合Hardy-Weirtberg平衡定律。结论 韩国人CYP1A1、CYP2E1、GSTM1、GSTT1基因分布与我国人群较为相近，半数以上人缺乏GSTM1和GSTT1基因，纯合缺失型频率超过印度人的3倍。     

中国南方汉族人群三种代谢酶基因多态性的分布特征

目的 了解中国南方某汉族人群3种肿瘤易感代谢酶基因多态性的分布特征。方法 以社区为基础的病例－对照研究中对照人群为分析对象，包括有血缘关系内对照290人和无血缘关系外对照404人。结果 3种代谢酶基因多态性在性别、居信地区、胃癌家族史、吸烟史等混杂因素中的频率差异均无显著性，个别组在年龄、饮酒史中的分布有差异，在相关性分析时需调整。CYP1A1 Ile/Val基因型频率为33.43%，Val/Val为5.62%，与中国人、日本人频率接近，但明显高于美洲、欧洲白人及美国黑人；GSTM1缺失基因频率为53.48%，在中国人群中也有一定差异；GSTT1缺失基因频率为45.78%，显著高于白种人和美国黑人。结论 中国南方汉族人CYP1A1突变基因频率和GSTT1缺失基因频率高于其它种族，而GSTM1缺失基因频率与其它种族的差异较小。     

Genetic Polymorphism of GSTP1: Prediction of Clinical Outcome to Oxaliplatin/5-FU-based Chemotherapy in Advanced Gastric Cancer

The aim of this study was to evaluate the predictive value of the polymorphism Glutathione S-transferase P1 (GSTP1) Ile¹⁰⁵Val on oxaliplatin/5-FU-based chemotherapy in advanced gastric cancer. Patients with advanced gastric cancer accepted oxaliplatin/5-FU-based chemotherapy as first-line chemotherapy were investigated. GSTP1 Ile¹⁰⁵Val polymorphism was detected by TaqMan-MGB probe allelic discrimination method. Response to treatment was assessed by disease controlled rate. Time to progression, overall survival and toxicities were recorded. Final patient outcomes were as follows: the allele frequencies of GSTP1 were ¹⁰⁵Ile/¹⁰⁵Ile 52%, ¹⁰⁵Ile/¹⁰⁵Val 41% and ¹⁰⁵Val/¹⁰⁵Val 7%. For patients with ¹⁰⁵Ile/¹⁰⁵Ile and those with at least one ¹⁰⁵Val allele, disease control rate was 39% and 71% (P=0.026), respectively; median time to progression was 4.0 and 7.0 months (P=0.002); median overall survival time was 7.0 and 9.5 months (P=0.002). Neurological toxicity was more frequently occurred in patients with two ¹⁰⁵Ile alleles (P=0.005). In conclusion, patients with at least one ¹⁰⁵Val allele have better prognosis and response to oxaliplatin/5-FU-based regimen as first-line treatment for patients with advanced gastric cancer.     

Combined analysis of EPHX1, GSTP1, GSTM1 and GSTT1 gene polymorphisms in relation to chronic obstructive pulmonary disease risk and lung function impairment

Smoking is considered as the major causal factor of chronic obstructive pulmonary disease (COPD). Nevertheless, a minority of chronic heavy cigarette smokers develops COPD. This suggests important contribution of other factors such as genetic predisposing. Our objective was to investigate combined role of EPHX1, GSTP1, M1 and T1 gene polymorphisms in COPD risk, its phenotypes and lung function impairment. Prevalence of EPHX1, GSTP1, M1 and T1 gene polymorphisms were assessed in 234 COPD patients and 182 healthy controls from Tunisia. Genotypes of EPHX1 (Tyr113His; His139Arg) and GSTP1 (Ile105Val; Ala114Val) polymorphisms were performed by PCR-RFLP, while the deletion in GSTM1 and GSTT1 genes was determined using multiplex PCR. Analysis of combinations showed a significant association of 113His/His EPHX1/null-GSTM1 (OR=4.07) and null-GSTM1/105Val/Val GSTP1 (OR =3.56) genotypes with increased risk of COPD (respectively P=0.0094 and P=0.0153). The null-GSTM1/ null-GSTT1, 105Val/Val GSTP1/null GSTT1, 113His/His EPHX1/null-GSTM1 and null-GSTM1/105Val/Val GSTP1 genotypes were related to emphysema (respectively P=0.01; P=0.009; P=0.008 and P=0.001). Combination of 113His/His EPHX1/null-GSTM1 genotypes showed a significant association with the decrease of Δ FEV1 in patients (P =0.028).In conclusion, our results suggest combined EPHX1, GSTP1, GSTM1 and GSTT1 genetic polymorphisms may play a significant role in the development of COPD, emphysema and decline of the lung function.     

抗原处理相关转运体等位基因与HLA-B27检测呈阳性的强直性脊柱炎的相关研究

目的探讨汉族人群抗原处理相关转运体(transporter associated with antigen processing, TAP)等位基因与HLA-B27及强直性脊柱炎(ankylosing spondylitis, AS)的相关性。方法用聚合酶链反应-序列特异性寡核苷酸探针杂交技术,对48例AS患者(B27+)及123名正常对照人群(B27+27名、B27-96名)进行TAP1、TAP2等位基因分型及变异位点氨基酸表型频率分析。结果汉族人群TAP1表现型主要为Ile/Ile和Asp/Asp,而TAP2则以Val/Val、Ala/Thr和Stop/Stop占优势。TAP1和TAP2至少各有4种等位基因型,分别为TAP1*0101、TAP1*0201、TAP1*0301、TAP1*0401和TAP2*0101、TAP2*0102、TAP2*0201、TAP2*0202。研究对象中有9.9%(17/171)TAP1探针无法定型,15.8%(27/171)TAP2无法定型,呈杂交空白。病例组与对照组间TAP等位基因型分布无差异(P＞0.05)。AS(B27     

Association of the GSTP1 and NQO1 polymorphisms and head and neck squamous cell carcinoma risk

The GSTP1 and NQO1 have been reported to be associated with an increased risk for smoking related head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to determine the effect of these metabolic gene polymorphisms on the risk of HNSCC. The study population included 294 histologically confirmed HNSCC cases and 333 controls without cancer. Genotyping analysis of the GSTP1 Ile105Val and NQO1 Trp139Arg genes was performed by polymerase chain reaction-based techniques on DNA prepared from peripheral blood. The Mantel-Haenszel chi2 test was used for statistical analysis. The allele frequencies of the GSTP1 and NQO1 polymorphisms were not statistically significant between cases and controls. In analyzing the association between smoking amounts and genetic polymorphisms, GSTP1 and NQO1 polymorphisms were associated with cigarette smoking amounts in cases. G allele containing genotypes in GSTP1 and T allele containing genotypes in NQO1 were associated with a tobacco dose-dependent increase in risk of HNSCC and these genotype distributions were statistically significant (p<0.05). We found that the GSTP1 105Val allele and NQO1 139Arg allele were associated with tobacco dose-dependent increase in risk of HNSCC. GSTP1 and NQO1 genotype polymorphisms may play an important role in the development of smoking related HNSCC.