肿瘤坏死因子α基因G-308A多态性与高血压相关性

目的探讨肿瘤坏死因子α(TNFα)基因G-308A多态性与高血压的相关性.方法放免法检测114例高血压患者和114健康对照者血浆TNFα水平,应用聚合酶联反应-限制性片段长度多态性(PCR-RFLP)方法检测TNFα基因G-308A多态性.结果与健康对照者相比较,高血压患者血浆TNFα水平增高(P<0.01);而TNFα基因G-308A基因型和等位基因的分布,高血压患者和健康对照者相比较无显著意义(P>0.05);高血压患者基因型间血浆TNFα水平、血压值比较无统计学差异(P>0.05).结论 TNFα基因G-308A多态性与高血压无关.     

原发性高血压患者的β-纤维蛋白原-455G／A基因多态性研究

目的　探讨 β-纤维蛋白原 - 4 5 5G/A基因多态性在山东地区汉族人群的分布以及该多态性与原发性高血压病的关系。方法　应用聚合酶链反应和限制性内切酶片段长度多态性技术 (PCR RFLP)检测了 14 8例健康人和 14 9例原发性高血压患者的 β Fg 4 5 5G/A基因多态性 ,比浊法测定血浆纤维蛋白原水平。 结果　β Fg 4 5 5G/A基因多态性分布在患病组和对照组均符合Hardy Weinberg平衡定律。在两组内A等位基因携带者血浆纤维蛋白原水平均显著高于GG基因型者。A等位基因频率在高血压组 (0 171)略高于正常对照组 (0 15 2 ) ,但差别无统计学意义 (P >0 0 5 )。结论　β Fg 4 5 5G/A基因多态可能不是原发性高血压的遗传易感标志。     

老年冠心病患者血浆中肿瘤坏死因子及其基因多态性的研究

目的　对老年冠心病患者血浆肿瘤坏死因子 (TNF)水平及其基因多态性进行分析 ,探讨其在冠心病发病中的作用。方法　用ELISA及PCR法测定 40例冠心病患者及 30例健康对照者血浆TNF水平及TNF等位基因频率。结果　TNF等位基因频率分布 ,两组之间比较差异无显著性意义 (P >0 .0 5 ) ,而血浆中TNF水平 ,冠心病组明显高于对照组 ,两组之间比较差异有显著性意义 (P <0 .0 0 1) 。结论　TNF基因多态性在冠心病发病机理中可能不起重要作用。TNFA或TNFB基因多态性与冠心病患者血浆TNF水平升高没有关系。     

老年高血压患者β-纤维蛋白原-455G/A基因多态性研究

目的　研究纤维蛋白原 (fibrinogen ,Fg) β 4 5 5G/A基因多态性在汉族人群中的分布及其与高血压脑缺血性并发症的关系。　方法　应用聚合酶链反应技术和限制性内切酶片段长度多态性技术检测了 10 8例单纯高血压患者 (高血压组 )、10 1例高血压合并缺血性脑卒中患者 (脑卒中组 )及 10 8例年龄、性别相匹配的健康对照者 (对照组 )的 β Fg 4 5 5G/A基因多态性 ,比浊法测定血浆Fg水平。　结果　血浆Fg水平在脑卒中组 (3 4 5 g/L)显著高于高血压组 (3 12 g/L)和对照组 (2 95g/L ,P <0 0 1)。各组内A等位基因携带者血浆Fg水平显著高于GG基因型者 (对照组 :3 2 5对 2 87g/L ;高血压组 :3 4 4对 2 97g/L ;脑卒中组 :3 76对 3 18g/L ,P <0 0 5或 0 0 1) ,且更易受吸烟等环境因素影响。β Fg 4 5 5G/A基因多态性分布在高血压组、脑卒中组和对照组均符合Hardy Weinberg平衡定律。A等位基因频率在脑卒中组 (0 2 6 7)显著高于对照组 (0 16 7,P <0 0 5 )。Logistic回归分析显示 ,存在此突变位点者发生脑卒中的危险为正常纯合子高血压者的 1 5 2 6倍。　结论　β Fg 4 5 5G/A基因多态性中的A等位基因可能是老年高血压患者并发缺血性脑血管疾病的遗传易感标志之一。     

纤维蛋白原β-455G/A基因多态性与高血压和冠心病的关系

为探讨纤维蛋白原Bβ链基因启动子区多态性位点Bβ - 4 5 5G A与高血压及其缺血性并发症的关系 ,应用聚合酶链反应—限制片长多态性技术对 14 9例高血压患者、12 4例高血压合并冠心病患者和 14 8例年龄、性别相匹配的健康人群进行纤维蛋白原 β - 4 5 5G A基因多态性分析 ;比浊法测定血浆纤维蛋白原水平。结果发现 ,冠心病组血浆纤维蛋白原水平显著高于高血压组 (P <0 .0 5 )和正常对照组 (P <0 .0 1) ,而高血压组与正常对照组之间差异无显著性 (P >0 .0 5 )。β - 4 5 5G A基因多态性分布在各研究组均符合Hardy Weinberg平衡定律。A等位基因频率在冠心病组 (0 .2 38)显著高于高血压组 (0 .171)和正常对照组 (0 .15 2 ;P均 <0 .0 5 )。各组内A等位基因携带者血浆纤维蛋白原水平显著高于GG基因型者 ,且冠心病组A等位基因携带者血浆纤维蛋白原水平更易受年龄等环境因素影响。Logistic回归分析发现 ,存在此突变位点的高血压患者发生冠心病的危险提高了 6 3.7%。结果提示 ,血浆纤维蛋白原水平增高是发生心血管疾病的重要危险因素 ,受遗传因素和环境因素共同影响。纤维蛋白原 β -4 5 5G A基因多态性可能通过改变血浆纤维蛋白原浓度影响冠心病的发生 ,说明遗传因素与冠心病发病相关。     

胃癌患者肿瘤坏死因子基因型与其血清水平的关系

目的 研究胃癌患者肿瘤坏死因子(TNF)-α308和TNF-β252基因型与血清TNF-α、β水平的关系.方法 收集病理诊断证实的57例胃癌患者,49例来白武汉大学中南医院,8例来自湖北省肿瘤医院.同时选取年龄与性别相匹配的18名健康体检者作为对照.采用限制性片段长度多态性聚合酶链反应(PCR-RFLP)方法检测患者外周静脉血.采用ELISA方法检测57例胃癌患者及18名对照者的血清TNF-α、β水平,比较胃癌患者各TNF基因型之间血清TNF水平的差异及其与对照者血清TNF水平的差异.分析胃癌患者TNF水平与临床病理特征的关系.结果 胃癌患者总体血清TNF-α水平较对照组明显增高(中位数445×10-3 μg/L比5×10-3 μg/L,P＜0.05),而且TNF-α308和TNF-β252各基因型(TNF α308 GA基因型6例、GG基因型51例,TNF-β252 GG基因型17例,GA和AA基因型各20例)的血清TNF-α水平较对照组也明显增高(P＜0.05),但血清总体TNF-β水平与对照组比较差异无统计学意义(P＞0.05).此外,TNF α308G/TNF-β252G和TNF-α308G/TNF-β252A单倍型胃癌患者血清TNF-α水平较对照组也明显增高(P＜0.05),其增高与血清总体TNF-α水平一样,与患者年龄、淋巴结转移显著相关(P＜0.05).TNF-α308A和TNF-β252G的高危等位基因携带者的TNF β水平与吸烟史显著相关(P＜0.05).结论 胃癌患者血清TNF-α水平增高与TNF-α308和TNF-β252基因型无显著相关性.TNF- α308G/TNF-β252G和TNF-d308G/TNF- β252A单倍型胃癌患者的血清TNF-α水平增高与年龄、淋巴结转移显著相关,提示TNF基因单倍型对胃癌TNF的表达及临床类型可能具有一定的影响.     

β-纤维蛋白原-455G/A基因多态性与Budd-Chiari综合征

目的　探讨 β 纤维蛋白原 (Fg) 4 5 5G/A基因多态性在影响Budd Chiari综合征 (BCS)患者血浆Fg水平中的作用以及其与BCS发病的关系。方法　经彩色多普勒超声检查和血管造影确诊的BCS患者 5 3例 ,健康对照组 10 5例。血浆Fg的测定应用酶反应法。采用酚 /氯仿抽提方法从白细胞中提取人基因组DNA ,运用PCR 限制性内切酶片段长度多态性技术检测 β Fg 4 5 5G/A基因多态性。结果　BCS患者组中 β Fg 4 5 5GA AA基因型频率与健康对照组相比差异有显著性(P <0 0 5 ,OR =2 0 4 ,95 %CI:1 0 3～ 4 0 2 ) ;BCS患者组平均血浆Fg水平显著高于健康对照组 (P <0 0 1)。无论BCS患者或健康对照 ,A基因携带者血浆Fg水平比同组GG基因型者显著升高 (0 0 1

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炎性相关细胞因子和心肌梗死微循环再灌注状态的关系

目的　观察急性心肌梗死 (AMI)患者梗死相关血管 (IRA)开通前后炎性细胞因子的动态变化及其与心肌组织水平灌注状态的关系。方法　 (1)测定 8例健康人和 2 2例AMI患者急诊冠状动脉介入治疗术 (PCI)前即刻 ,术后 12、2 4h ,血浆白细胞介素 (IL) 1β、肿瘤坏死因子 (TNF)α、IL 10的变化。 (2 )按照再灌注后 2h心电图ST段回落是否 >70 % ,将 2 2例AMI患者分为 :A组 (ST回落≥ 70 % )12例和B组 (ST回落 <70 % ) 10例 ,比较两组患者IL 1β、TNFα、IL 10的变化幅度。 结果　 (1)治疗前A、B两组AMI患者血浆TNFα、IL 10略高于健康对照组 ,但差异无统计学意义 (P >0 0 5 ) ;而IL 1β显著高于健康对照组 (P <0 0 5 ) ;再灌注后 12、2 4hA、B两组血浆IL 1β和TNFα均较术前显著增高 (P <0 0 1,P <0 0 5 ) ,B组血浆IL 10较术前显著增高 (P <0 0 5 ) ,A组则无此变化 (P >0 0 5 )。 (2 )A、B两组间比较 ,治疗前TNFα、IL 1β、IL 10差异均无显著性 (P >0 0 5 ) ;成功PCI、IRA血流达TIMI 3级者 ,B组患者血浆IL 1β、TNFα、IL 10 ,在再灌注 12h显著高于A组 (P <0 0 1,P <0 0 5 ,P <0 0 5 ) ,再灌注 2 4h ,IL 1β、IL 10仍然高于A组 (P <0 0 5 )。 (3)A、B两组患者抗炎因子IL 10的升高幅度均显著低于致炎     

老年抑郁症患者血浆脑源性神经营养因子水平与G196A基因多态性的相关性

目的探讨老年抑郁症患者血浆脑源性神经营养因子(BDNF)水平与G196A基因多态性的相关性。方法选择2016年1月至2017年4月新乡医学院第二附属医院确诊的90例老年抑郁症患者作为研究组,同期60名老年健康体检者作为对照组,采用酶联免疫吸附试验(ELISA)测定血浆中BDNF水平、聚合酶链反应-限制性片段长度多态性(PCR-RFLP)检测血清G196A基因多态性,并进行Pearson相关性及多元逐步回归分析。结果与对照组比较,研究组血浆BDNF水平显著降低(P0. 05),患者血清中的G196A基因型分布频率、A等位基因分布频率和等位基因携带分布频率均发生了明显改变(P0. 05);血浆BDNF水平与G196A等位基因分布频率呈负相关(r=-0. 674,P0. 05),血浆BDNF水平与G196A基因多态性密切相关(P0. 05)。结论血浆BDNF与G196A基因多态性参与老年抑郁症的发生,且BDNF水平与G196A基因多态性密切相关,可作为老年抑郁症的生物指标。     

血管紧张素转化酶2基因多态性与高血压合并缺血性脑卒中

目的研究血管紧张素转化酶2（angiotention-converting cnzyme 2，ACE2）基因G9570A多态性与中国南方高血压患者发生缺血性脑卒中的关系。方法采用聚合酶链反应和限制性片段长度多态性的方法，检测单纯原发性高血压136例及原发性高血压合并缺血性脑卒中患者139例的ACE2基因．同时测定颈动脉内膜中层厚度及血浆血管紧张素Ⅱ水平，并进行组间对照研究，探讨ACE2基因G9570A多态性与原发性高血压患者中缺血性脑卒中发病的关系。结果原发性高血压合并缺血性脑卒中组A等位基因频率分布高于原发性高血压组（P〈0．05）；两组ACE2基因型分布不同（P〈0．05）；原发性高血压合并缺血性脑卒中组携带A／AA基因者血浆血管紧张素Ⅱ水平高于携带G／GG基因者（P〈0．05）。在男性原发性高血压合并缺血性脑卒中组携带A基因者颈动脉内膜中层厚度高于携带G基因者（P〈0．05）。结论原发性高血压患者中，携带A／AA基因者发生缺血性脑卒中的危险性相对较大．可能与其血管紧张素Ⅱ水平较高有关。     

Relationship of the tumor necrosis factor-alpha -308 A/G promoter polymorphism with insulin sensitivity and abdominal fat distribution in Japanese patients with type 2 diabetes mellitus

We investigated the relationship of the A/G variant of the tumor necrosis factor-alpha (TNF-alpha) gene promoter at position -308 with insulin resistance and abdominal fat distribution in type 2 diabetic patients in the Japanese population. The TNF-alpha polymorphism was evaluated by polymerase chain reaction-restriction fragment length polymorphism in 142 healthy volunteers and 132 type 2 diabetic patients. Insulin sensitivity was assessed by homeostasis model assessment (HOMA) index in healthy subjects and hyperinsulinemic euglycemic clamp in type 2 diabetic patients. Abdominal fat distribution was evaluated by computed tomography (CT) scanning in diabetic patients. The TNF-alpha polymorphism was detected in three healthy volunteers and three type 2 diabetic patients, all of them being heterozygotes. There was no significant difference in allele frequencies of the -308 polymorphism between healthy subjects (0.0106) and type 2 diabetic patients (0.0114). HOMA index was no significant difference between healthy subjects with and without polymorphism (1.09 +/- 0.03 vs. 1.02 +/- 0.05). Glucose infusion rate (GIR), an index of insulin sensitivity, was not significantly different between diabetic patients with and without TNF-alpha polymorphism (40.4 +/- 4.1 vs. 45.0 +/- 1.8 micromol/kg per min). Moreover, no remarkable effect of TNF-alpha polymorphism on abdominal fat distribution was observed in diabetic patients. These results suggest that A/G heterozygotes of the TNF-alpha gene promoter at position -308 play no major role in the pathogenesis of insulin resistance or abdominal fat distribution in Japanese type 2 diabetic patients.     

Response to combination therapy with interferon alfa-2a and ribavirin in chronic hepatitis C according to a TNF-alpha promoter polymorphism

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is involved in the pathogenesis of chronic active hepatitis C. Polymorphisms in the promoter region of the TNF-alpha gene can alter the TNF-alpha expression and modify the host immune response. The present study aimed at the correlation of the G308A TNF-alpha polymorphism with the response to antiviral combination therapy in chronic hepatitis C. PATIENTS AND METHODS: 62 patients with HCV and 119 healthy unrelated controls were genotyped for the G308A TNF-alpha promoter polymorphism. The patients received 3 x 3 million units of interferon alfa-2a and 1,000-1,200 mg ribavirin daily according to their body weight. A response was defined as absence of HCV-RNA and normalization of S-ALT after 6 months of combination therapy. RESULTS: With respect to the allele and genotype frequency, a significant difference was not observed between controls and patients with chronic hepatitis C. Furthermore, such a difference was also not observed if responders and non-responders to antiviral therapy were compared. CONCLUSIONS: The promoter polymorphism of the TNF-alpha gene investigated herein is equally distributed in healthy individuals and patients with hepatitis C and does not seem to predict the response to therapy with interferon alfa-2a and ribavirin.     

Tumor necrosis factor-alpha and Interleukin-10 gene promoter polymorphisms in Turkish rheumatoid arthritis patients

Tumor necrosis factor and interleukin 10 have been implicated in the pathogenesis of rheumatoid arthritis (RA). Certain single-nucleotide polymorphisms (SNPs) within the promoter region of the IL-10 and TNF genes have been associated with altered levels of circulating IL10 and TNF. We aimed to explore the association of IL-10 and TNF-alpha polymorphisms in Turkish RA patients. We analyzed the association of TNF-alpha (-308G/A, -238G/A, -376G/A) and IL10 (-1082G/A, -819C/T, -592C/A) polymorphisms in 98 Turkish patients with rheumatoid arthritis and 122 healthy subjects using ARMS-PCR. The correlation of these findings with RF positivity and erosive disease in RA patients was also sought. A significant association was found between having RA and -1082 G allele (p = 0.008; OR = 1.44, 95% CI 1.11-1.86). There was no association between RA and -819C/T polymorphism. Significant differences were observed in IL10 GCC and ACC haplotypes distribution between RA and control subjects (p = 0.006; OR = 1.46, 95% CI 1.13-1.89 and p = 0.011; OR = 1.43, 95% CI 1.09-1.88, respectively). No statistically significant association was found between TNF-alpha 308G/A, -238G/A, -376G/A polymorphisms and RA. No significant association was found between RF positivity and erosive disease and TNF-alpha, IL10 gene polymorphisms. In addition, when combined genotypes were analyzed, no significant difference was found between RA patients and healthy controls. Our findings suggest that IL-10 1082 G/A polymorphism or GCC, ACC haplotypes may be associated with RA in Turkish patients.     

Lack of association of tumor necrosis factor alpha gene polymorphism in patients with rheumatoid arthritis in central Taiwan

The aim of this study was to investigate the association of tumor necrosis factor alpha (TNFalpha) gene promoter polymorphisms in Chinese patients with rheumatoid arthritis (RA) in central Taiwan. A total of 106 RA patients and 253 normal controls were studied. Polymerase chain reaction (PCR)-based restriction analysis was used to identify A/G polymorphism at position 308 in the promoter region of the TNFalpha, which is located at 6q21.3. For the genotype of TNFalpha-308 polymorphism, there was no statistically significant difference between RA patients and normal controls (Fisher's exact test, P=0.82). Additionally, no statistical association in the distribution of TNFalpha-308 polymorphism between rheumatoid factor (RF)-positive and -negative patients was noted. The lack of an association of TNFalpha-308 polymorphism with RA and RF in our study implies that TNFalpha-308 polymorphism cannot serve as a candidate gene marker for screening RA patients in Taiwan.     

Association of TNF-alpha -308 G/A and IL-4 -589 C/T gene promoter polymorphisms with asthma susceptibility in the south of Iran.

BACKGROUND: Both tumor necrosis factor alpha (TNF-alpha) and interleukin (IL) 4 have been implicated in the pathogenesis of asthma. Furthermore, a G/A substitution at position -308 of the TNF-alpha gene promoter and a C/T substitution at position -589 of the IL-4 gene promoter have been associated with increased production of TNF-alpha and IL-4, respectively. OBJECTIVE: The aim of the present study was to analyze the association between TNF-alpha-308 G/A and IL-4-589 C/T polymorphisms and susceptibility to asthma in a group of patients from southern Iran. METHODS: We analyzed the frequency of TNF-alpha -308 G/A and IL-4-589 C/T polymorphisms in a total of 203 asthmatic patients compared to 113 nonasthmatic control subjects. RESULTS: An association was observed between the TNF-alpha -308 G/A polymorphism and susceptibility to asthma in patients with a ratio between forced expiratory volume in 1 second and forced vital capacity of less than 75% compared with normal subjects; however, the association did not achieve statistical significance (P = .054). The IL-4-589 C/T polymorphism was associated with asthma susceptibility (P = .02). In addition, the association between this polymorphism and asthma severity approached statistical significance (P = .07). CONCLUSION: These results provide further evidence for a role of TNF-alpha-308 G/A and IL-4-589 C/T polymorphisms in susceptibility to and severity of asthma. Further studies involving a larger number of patients may help to confirm our observations.     

-308 Nco I polymorphism of tumour necrosis factor alpha in overweight Caucasians

We investigated whether a polymorphism in the promoter region of the TNFalpha gene (-308 A/G) is associated with reduced weight loss in obese Australian subjects on an energy restricted diet. 189 healthy subjects and 91 subjects with type II diabetes were genotyped for the -308 Nco I polymorphism using PCR-RFLP techniques. A subset of these subjects (211 females and 45 males), were placed on a 30% energy restricted diet (6200 kJ) for 12 weeks. Subjects were assessed every 2 weeks and changes in body weight, waist circumference and BMI were used as determinants of weight loss. Fasting plasma was analysed for glucose, insulin, lipids and free fatty acids. 64% of subjects were GG homozygotes, 31% were AG heterozygotes and 5% were AA homozygotes. There was no significant difference between the allele frequency in healthy subjects (0.21) and type 2 diabetic patients (0.24). The presence of the -308 A/G polymorphism did not significantly influence initial BMI, the amount of weight lost (GG, 8.1+/-0.65 kg, AG, 6.9+/-0.77 kg, AA, 7.6+/-0.12 kg), waist circumference or any metabolic variable. The AA variant at position -308 in the promoter region of the TNFalpha gene does not influence the amount of weight lost in overweight and obese men and women on a 30% energy restricted diet.     

Tumour necrosis factor-alpha (TNF-alpha) levels and influence of -308 TNF-alpha promoter polymorphism on the responsiveness to infliximab in patients with rheumatoid arthritis

OBJECTIVE: To investigate the influence of -308 tumour necrosis factor-alpha (TNF-alpha) promoter polymorphism and circulating TNF-alpha levels in the clinical response to the infliximab treatment in patients with rheumatoid arthritis (RA). METHODS: One hundred and thirty-two RA patients were genotyped for TNF-alpha promoter by polymerase-chain reaction restriction fragment-length polymorphism (PCR-RFLP) analysis. Ten patients with the -308 TNF-alpha gene promoter genotype G/A, and 10 with the G/G genotype were selected and received 3 mg/kg of infliximab at Weeks 0, 2, 6, and 14. RESULTS: Both groups showed a significant improvement with treatment in all variables studied. Total mean TNF-alpha levels increased significantly with respect to basal levels in most of patients after treatment [probability (p)=0.04]. Only patients from G/A showed a statistically significant correlation between ACR 50 and the increase of TNF-alpha levels (p<0.03). CONCLUSION: A relationship was detected between ACR criteria of improvement and increased circulating TNF-alpha levels in RA patients subjected to anti-TNF-alpha therapy.     

A polymorphism in the promoter of the tumor necrosis factor-alpha gene (-308) is associated with coronary heart disease in type 2 diabetic patients

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a key cytokine in the inflammation process of atherosclerosis. Through its effects on lipid metabolism, insulin resistance and endothelial function, it might be involved in coronary heart disease (CHD). A biallelic polymorphism within the promoter of TNF-alpha locus at the position -308 has been reported to be associated with TNF production. We have studied the association of this polymorphism with CHD in a Mediterranean non-diabetic and type 2 diabetic population. METHODS: Three hundred and forty one CHD patients (106 with type 2 diabetes), 207 healthy matched control subjects and 135 type 2 diabetic patients without CHD were evaluated. A single nucleotide polymorphism at the promoter TNF-alpha (-308) was analyzed by RFLP-PCR. RESULTS: TNF-alpha (-308) genotype and allele frequencies for A carriers were higher in CHD patients than those observed in the control group (32.3 vs. 23.2%, P=0.03; and 18.8 vs. 12.1%, P=0.0047; respectively) independently of other risk factors. Genotypic analysis revealed that CHD patients with type 2 DM displayed a greater prevalence of the -308 TNF-alpha A allele (40.6%) than controls (23.2%) or CHD patients without type 2 DM (28.5%) (P=0.0056). The odds ratio for CHD in type 2 diabetic patients in presence of -308 TNF-alpha A allele was 2.86 (CI 95%: 1.55-5.32). This difference was observed mainly in diabetic women for the A allele carriers (OR: 4.29; CI 95%: 1.6-11.76). CONCLUSIONS: These results suggest that -308 TNF-alpha gene polymorphism may contribute to CHD risk in patients with type 2 diabetes and it could constitute an useful predictive marker for CHD in type 2 diabetic women.     

血管紧张素Ⅱ 1型受体基因单核苷酸多态性与原发性高血压和冠心病的相关研究

目的研究血管紧张素Ⅱ1型受体基因（AT1）单核苷酸多态性（SNP）与华东地区汉族人原发性高血压和冠心病的相关性。方法对AT1基因的启动子区、5’非翻译区、外显子及邻近内含子和3’非翻译区设计引物进行分段扩增,采用直接测序法在20个随机样本中检测AT1基因的SNP,选择所发现的SNP在213例单纯高血压、171例高血压合并冠心病和200例正常对照中进行基因分型,以期探讨ATl基因在原发性高血压和冠心病发病中的作用。结果共检出8个SNP,其中6个在启动子区,1个在编码区,1个在3’非翻译区,分别对SNP6（A-153G）、SNP7（T573C）和SNP8（A1166C）行基因分型,显示位于启动子-153G等位基因在原发性高血压合并冠心病组中的频率是17．8％,在对照组中是11．5％（P〈0．05）,而T573C和A1166C多态则未显示有统计学意义。结论血管紧张素Ⅱ1型受体基因启动子-153位A被G替代可能与华东汉族人原发性高血压患者合并冠心病相关。     

TNF-alpha promoter region gene polymorphisms in HIV-positive patients with lipodystrophy

OBJECTIVE: The pathogenic mechanisms underlying lipodystrophy in HIV-positive patients are largely unknown. TNF-alpha has many actions that are consistent with the features of lipodystrophy; therefore, an analysis was carried out to determine whether functionally active polymorphisms in the promoter region of the TNF-alpha gene are associated with the development of lipodystrophy. DESIGN: Genetic case-control association study. METHODS: Individuals were genotyped for the -238 and -308 polymorphisms in the TNF-alpha gene using polymerase chain reaction-restriction fragment length polymorphism analysis. The genotype and allele frequencies for 61 HIV-positive patients with lipodystrophy were compared with (a) 35 HIV-positive patients with no evidence of lipodystrophy and (b) 239 healthy HIV-negative individuals. RESULTS: The frequency of the variant rare -238 allele was significantly different (P = 0.01) in HIV-positive patients with lipodystrophy than in those without lipodystrophy. At the genotype level, a trend towards a difference between patients with and without lipodystrophy was observed (chi2 for linear trend 5.2, P = 0.02). For the -308 polymorphism, no difference was found in genotype and allele frequencies between HIV patients with and without lipodystrophy. CONCLUSIONS: The data suggest that the -238 (but not the -308) promoter region TNF-alpha gene polymorphism is a determinant in the development of HIV-related lipodystrophy. However, the results need to be confirmed in larger numbers of patients as well as in an ethnically diverse population.