WNK4基因G1816T多态性与高血压的关联研究

目的阐明WNK4基因G1816T多态性与原发性高血压的关系。方法2001年3～10月选择中国东北高血压病高发地区辽宁省彰武县采集的259例原发性高血压患者和235名健康对照组的血样应用聚合酶链反应-限制性长度片段长度多态性分析（PCR—RFLP）方法检测G1816T多态，结果经测序验证，同时检测所有人群的血糖、血脂等生化指标。结果原发性高血压组WNK4基因G1816T多态T等位基因频率显著高于对照组（25．9％对20．2％，P=0．035）；AS和SS基因型与收缩压及舒张压升高密切相关（P分别为0．041和0．032）。结论WNK4基因G1816T多态与高血压密切相关。     

WNK4基因多态性与新疆哈萨克族原发性高血压的关系

目的 探讨新疆哈萨克族WNK 4(with no K=lysine kinase)基因内含子10(intron10)多态性与原发性高血压间的关系,了解该基因多态性在哈萨克族人群中的分布情况.方法 采用直接测序法测定WNK 4基因intron10序列,确定单核苷酸多态性位点及类型,应用多聚酶链反应、限制性片段长度多态性技术(PCR-RFLP)对该位点进行基因分型,其中原发性高血压患者191例(高血压组)、健康对照组173例.结果 在WNK 4基因intron10发现一多态性位点(17号染色体上碱基1156666,G→A);PCR-RFLP分型,GG、GA、AA各基因型在哈萨克族高血压组和健康对照组的频率分别为88.0%、11.0%、1.0%和91.9%、8.1%、0%,差异无统计学意义(均为P＞0.05);A等位基因频率分别为6.5%和4.0%,差异无统计学意义(P＞0.05).结论 WNK 4基因intronl0多态性可能不是新疆哈萨克族原发性高血压的遗传易感指标.     

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。     

G蛋白β3亚单位基因C825T多态性与高血压患者的肥胖无关

目的　探讨G蛋白β3亚单位基因C82 5T多态性与原发性高血压患者肥胖的相关关系。 方法　采用聚合酶链反应结合限制性内切酶片段长度多态分析方法检测 14 7例健康人和 32 1例高血压患者的G蛋白 β3亚单位C82 5T多态性 ,并测定高血压患者的体质指数、总胆固醇、甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇及空腹血糖浓度。结果　高血压组G蛋白β3亚单位C82 5T多态性中基因型频率 (CC为 2 8.7% ,CT为 5 2 % ,TT为19.3% )、等位基因频率 (C为 5 4 .6 72 % ,T为 4 5 .33% )与正常对照组基因型频率 (CC为 2 7.2 % ,CT为 4 6 .9% ,TT为 2 5 .9% )、等位基因频率 (C为 5 0 .7% ,T为 4 9.3% )比较无显著性差异 (P >0 .0 5 ) ;CC基因型患者的体质指数、血脂水平与CT +TT基因型患者比较无显著性差异 (P >0 .0 5 )。结论　G蛋白 β3亚单位基因C82 5T多态性可能与高血压患者的肥胖无关     

蒙族高血压患者内皮型一氧化氮合酶(eNOS)基因多态性研究

目的旨在探讨一氧化氮合酶(eNOS)基因(G894T、T786C)多态性与中国蒙古族高血压患者的相关性。方法采用聚合酶链反应和限制性酶切的片段长度多态分析方法检测蒙族高血压患者100例和健康人50例的一氧化氮合酶(eNOS)基因(G894T、T786C)多态性。结果一氧化氮合酶基因T894G(GT、TT)、T786C(CT、CC)基因型及T、C等位基因频率在高血压组显著高于对照组(P <0．05)。同时具有eNOS894TT、786CC和894TG、786TC基因型者高血压组比对照组多,差异有显著性(P<0．05)。结论一氧化氮合酶基因T894G、T786C基因多态性与蒙族高血压相关,但尚需在更大的人群中进一步验证。     

WNK1基因Pro1056Thr多态与高血压病的关联研究

目的探讨WNK1基因Exon13Pro1056Thr多态是否与高血压病有关。方法为研究WNK1基因多态与原发性高血压的相关性，我们通过病例对照研究在河南省信阳市农村入选高血压病患者820例，正常对照772例。应用PCR-RFLP方法检测WNK1基因Exon13Pro1056Thr多态性，结果经测序验证。应用Logistic回归分析该多态与高血压病的关联性。结果WNK1基因Exon13Pro1056Thr与高血压病的易感性显著相关（优势比1．42，95％可信区间1．16-1．74，P=0．001），应用1ogistic回归校正传统危险因素后，这一关联性依然存在（优势比1．39，95％可信区间1．10—1．77，P=0．007）。WNK1基因Exon13Pro1056Thr A等位基因携带者增加高血压病的易感性。结论WNK1基因Exon13Pro1056Thr多态与高血压病密切相关，A等位基因是高血压病的独立危险因素。因而，WNK1基因可能参与了高血压病的发病过程。     

内皮型一氧化氮合酶基因894 G→T多态性与原发性高血压的关系研究

目的 :探讨内皮型一氧化氮合酶 (eNOS)基因 894G→T多态性与原发性高血压 (EH)之间的关系。　　方法 :应用多聚酶链反应限制性片段长度多态性技术对湖北地区汉族 1 0 3例EH患者 (EH组 )及 74名健康者 (正常对照组 )的eNOS外显子 894位进行基因分型 ,并采用生化技术测定其血脂水平。　　结果 :①EH组T等位基因频率为 0 2 6 2及GT、TT基因型频率分别为 0 4 2 7,0 0 4 9显著高于正常对照组的 0 1 2 8和 0 2 57,有极显著性差异 (P <0 0 1 ) ;②在EH组中GT +TT基因型者的舒张压显著高于GG基因型者有显著性差异(P <0 0 5) ;③收缩压、舒张压、eNOS基因 894G→T基因点突变属原发性高血压的独立危险因素。　　结论 :eNOS基因 894G→T多态性与中国人原发性高血压的发生相关。     

多巴胺受体D1基因—48A／G多态性与原发性高血压病的关联研究

目的探讨多巴胺受体D1基因 4 8A/G多态性与原发性高血压病相关性。方法运用聚合酶链反应一限制性片段长度多态性法 (PCR RFLP)分析了解 - 4 8A/G基因型在原发性高血压病组和正常血压对照组的分布情况。结果等位基因A ,G在原发性高血压病组和对照组的分布频率分别为 0 78,0 2 2和 0 86 ,0 14 ,基因频率分布符合Hardy Weinberg平衡 ,样本具有群体代表性 ,两组人群的基因型和等位基因频率存在明显统计学差异 (P <0 0 1,P <0 0 1)。原发性高血压组中G等位基因 ,舒张压明显高于A等位基因 (P <0 0 5 )。结论在中国人群中 ,多巴胺受体D1基因 4 8A/G多态性与原发性高血压病显著性相关     

转化生长因子β1基因多态性与原发性高血压关系的研究

目的探讨转化生长因子β1(TGF-β1)基因第1外显子 869T/C及 915G/C多态性与原发性高血压的关系。方法采用序列特异性引物聚合酶链反应(PCR-SSP)技术,检测120例原发性高血压患者和130例健康对照者转化生长因子β1的基因多态性。结果TGF-β1基因 869T/C多态性在两组人群中的分布存在显著性差异(P<0·05),等位基因频率的相对风险分析发现,C等位基因携带者患原发性高血压的风险是T等位基因的1·628倍(OR=1·628,95%CI:1·143～2·319),携带C等位基因的原发性高血压患者收缩压水平显著高于不携带者〔(162·4±18·3)mmHgvs(156·1±16·9)mmHg,P<0·05〕;而TGF-β1基因 915G/C位点多态性在原发性高血压组和正常人群中的分布差异无显著性。结论TGF-β1基因 869T/C多态性与原发性高血压的发病具有相关性,其中C等位基因可能是原发性高血压发病的遗传易感基因;携带C等位基因的个体可能通过促进收缩压的升高进而增加了原发性高血压的发病风险。     

老年高血压病与P22phox-930A/G多态性

目的　探讨NAD(P)H氧化酶P2 2 phox亚单位基因启动子区 930A/G多态性与老年及老年前期原发性高血压的关系。方法　应用多聚酶链反应 限制性片段长度多态性 (PCR RFLP)检测 1 51例高血压患者 (老年期高血压患者 83例 ,老年前期高血压患者 68例 )和 1 2 0例健康者 (老年期对照 66例 ,老年前期对照 54例 )P2 2 phox 930A/G基因多态性 ,生化技术测定血脂。结果　老年及老年前期高血压病组GG基因型频率分别为42 2 %和 42 6 % ,G等位基因频率分别为 65 1 %和 65 4% ,明显高于相应年龄对照组的 33 3 %和 33 4%以及 53 %和 51 9%〔与相应年龄对照组基因型分布频率比较 χ2 =1 9 64(P <0 0 1 )及 χ2 =6 0 7(P <0 0 2 ) ;等位基因分布频率比较 χ2 =4 42 (P <0 0 5)及 χ2 =4 61 (P <0 0 5)〕。结论　P2 2phox 930A/G基因多态性与高血压病有明显相关性 ,G等位基因是高血压病的危险因素 ;未发现老年前期高血压病组基因型间的血脂水平有差异 ,但在老年高血压病组中 ,收缩压高于对照组 ,高密度脂蛋白低于对照组。     

WNK4 Polymorphisms and Essential Hypertension in the Uyghur Population

Subtle genetic variants in ion-channel genes might be at the origin of less rare forms of hypertension in the general population. To test this hypothesis, we observed the role of several important polymorphisms (T1155547C at exon7, G1155942T at exon8, G1156666A at intron10, and C1163527T at intron14) of WNK4 (with-no-kinase) gene on the prevalence of essential hypertension in a Chinese minority ethnic group—the Uyghur population. We did not find a significantly different distribution of genotype and allele frequency of T1155547C, G1155942T, and G1156666A between hypertensives and controls, but we observed a significantly higher frequency of T allele in hypertensive subjects than controls (8.4% vs. 5.7%) (P = 0.02) of C1163527T polymorphism at intron14. Compared with the individuals with two C allele, individuals with at least one T allele show 55% of excess risk in developing hypertension (OR = 1.56, 95% CI:1.06–2.28). In a further analysis, we did not observe a significantly higher or lower odds ratio of haplotype frequency in the hypertensives than in the controls across haplotype encompassing G1155942T, G1156666A, and C1163527T. Thus, a positive association of C1163527T at intron 14 reveals that the WNK4 gene might be involved in the prevalence of essential hypertension in the Uyghur population. Further study should be conducted to observe the role of this gene on hypertension in other populations.     

WNK4 intron 10 polymorphism is not associated with hypertension

A polymorphism in intron 10 of the serine-threonine kinase with no lysine (K) 4 gene WNK4 (G-->A, base 1156666 on chromosome 17) has recently been associated with essential hypertension in a white American population. We have attempted to replicate this finding in a well characterized cohort of 184 unrelated hypertensive Australians of British extraction in which biological power was enhanced by them each having 2 hypertensive parents. Controls were 219 normotensive ethnically matched subjects whose parents were both normotensive. Genotyping was performed using the homogeneous MassEXTEND Assay. This showed a frequency of 0.10 for the minor allele in each group (P=0.88). Moreover, blood pressure, body mass index, sex, and plasma lipid levels were similar across genotypes. In conclusion, our study provides no support for an association of the intron 10 variant of WNK4 with essential hypertension in the Anglo-Australian population studied.     

Association of CTLA4 gene A-G polymorphism with type 1 diabetes in Chinese children

OBJECTIVE: The CTLA4 (cytotoxic T lymphocyte associated antigen-4) gene encodes the T cell receptor involved in the control of T cell proliferation and mediates T cell apoptosis. Thus it is a strong candidate gene for T cell-mediated autoimmune disease. There is polymorphism at position 49 in exon 1 of the CTLA4 gene, providing a A-G exchange. This polymorphism is reportedly associated with type 1 diabetes in Caucasians but not in a small data set of Chinese. We wished to test this polymorphism in a larger and more homogeneous data set of Chinese children with type 1 diabetes and normal adult controls. DESIGN: A population-based case-control study of a CTLA4 gene 49 A-G polymorphism was performed to look for an association with type 1 diabetes in Chinese children. PATIENTS: We analysed this polymorphism in 253 unrelated children (128 boys) with type 1 diabetes (age at diagnosis 7.1 +/- 3.7 years) and 91 randomly selected normal adults. All individuals were Han Chinese. RESULTS: The genotype and gene frequencies of children with type 1 diabetes differed significantly from those of adult controls (P = 0.0091 and P = 0.0051, respectively). Genotype CTLA4 49 G/G and G allele conferred a risk of type 1 diabetes (RR = 2.13, 95% CI = 1.31-3.46, P = 0.0022; RR = 1.68, 95% CI = 1.17-2.43, P = 0.0051, respectively). CONCLUSIONS: This study demonstrates that CTLA4 49 A-G polymorphism is associated with type 1 diabetes in Han Chinese children. The CTLA4 49 G allele confers an increased risk of type 1 diabetes.     

环氧化物水解酶基因多态性与新疆哈萨克族、汉族原发性高血压的相关性研究

目的 探讨环氧化物水解酶( EPHX2)基因rs751141位点基因多态性与新疆哈萨克族、汉族原发性高血压之间的相关性.方法 分别选择新疆哈萨克族267例,汉族原发性高血压患者368例,同时选取哈萨克族、汉族正常对照组284例和348例,用Hardy-Weinberg平衡检验样本群体代表性,采用TaqMan探针法对EPHX2基因rs751141位点基因多态性进行检测.结果 新疆汉族原发性高血压组rs751141G/A多态位点GA+ AA基因型的分布频率(40.2％)明显低于正常对照组(52.0％),差异具有统计学意义(P＜0.01),而新疆哈萨克族原发性高血压组与正常对照组中rs751141G/A基因多态性比较差异均无统计学意义(P＞0.05).结论 EPHX2基因rs751141 G/A等位基因多态性与新疆哈萨克族原发性高血压无显著相关性,EPHX2基因rs751141G/A等位基因多态性与新疆汉族原发性高血压均显著相关,EPHX2基因rs751141位点的A等位基因可能是新疆汉族原发性高血压病的独立的保护因子.     

E-选择素第2外显子G98T基因多态性与高血压病的相关性研究

目的 观察原发性高血压病(EH)患者E-选择素(E-selectin)基因第2外显子G98T多态性,并探讨高血压发病的遗传学机制。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155例高血压患者和160例正常对照者E-selectin基因型,生化技术测定血脂水平。结果 E-selectin基因型GG、GT频率在高血压组和对照组分别为85.2％、14.8％和92.5％、7.5％;等位基因G、T频率在高血压组和对照组分别为92.6％、7.4％和96.3％、3.7％。基因型频率和等位基因频率在高血压组和对照组比较差异均有显著性(P<0.05)。结论 E-selectin第2外显子G98T基因多态性与高血压的发病有关性,T等位基因可能是高血压发病的危险因素之一。     

Significance of angiotensinogen gene haplotypes and genotypes combinations in hypertension

OBJECTIVE: Renin-angiotensin system gene polymorphisms are associated with essential hypertension; angiotensinogen gene variants are considered potential genetic risk factors. The aim of this study was to investigate the contribution of the G-6A, T174M, M235T polymorphisms, genotypic interactions, and haplotypes toward essential hypertension. METHODS: In a case-control design, 810 consecutive ethnically matched unrelated individuals comprising 450 hypertensive patients and 360 controls were recruited. Genotyping by polymerase chain reaction-restriction fragment length polymorphism, genotypes combinations, and haplotypes analyses were performed. Plasma renin activity and plasma aldosterone concentration were measured. RESULTS: The G-6A and M235T polymorphisms differed significantly (P = 0.007, odds ratio = 1.9, 95% confidence interval = 1.2-2.9; P < 0.0001, odds ratio = 3.7, 95% confidence interval = 2.3-5.7, respectively), wherein the -6A and 235T mutant alleles were over-represented in hypertensive patients (P < 0.0001, each). Genotypes combinations of six wild-type alleles versus the remaining resulted in odds ratio of 2.4 (P < 0.0001), further mutant alleles based combinations linearly correlated with systolic, diastolic, and mean blood pressure. Over-representation of the haplotypes, namely, A/174T, 174T/235T, A/235T, and A/174T/235T in hypertensive patients and G/174T, 174T/235M, G/235M, and G/174T/235M in controls, was identified as risk and protective haplotypes (P < 0.0001, each), respectively. The patients had significantly higher plasma aldosterone concentration and lower plasma renin activity (P < 0.0001), the former correlated with -6A and 235T alleles (P < 0.0001). CONCLUSION: The interaction among G-6A, M235T and T174M polymorphisms in combinations or haplotypes emerged significant. These findings, conjoint with significant high plasma aldosterone concentration and low plasma renin activity, suggest low-renin hypertension in our study population.     

The 825C/T polymorphism of the G-protein subunit beta3 is not related to hypertension.

A polymorphism at position 825 (C-->T) of the cDNA that encodes the beta3 subunit (GNB3) of the pertussis toxin-sensitive G protein was recently shown to be associated with human hypertension. To verify this finding and to investigate whether this polymorphism could also be associated with coronary heart disease, we analyzed the GNB3 variant in subjects from 2 previously described studies: Projet d'Etude des Gènes de l'hypertension Artérielle Sévère à modérée Essentielle (PEGASE), a case-control study of moderate to severe hypertension (681 cases and 308 controls), and Etude Cas-Témoins de l'Infarctus du Myocarde (ECTIM), a case-control study of myocardial infarction (MI) (564 cases and 633 controls). Genotyping was performed with allele-specific oligonucleotides. Genotype and allele frequencies were in Hardy-Weinberg equilibrium in all groups. Allele and genotype frequencies did not differ significantly between case patients with essential hypertension or MI and control subjects. In the ECTIM study, the 825T allele frequencies in cases and controls from Belfast, Northern Ireland, were 0.31 and 0.30 (P=0.79), respectively; the corresponding frequencies in cases and controls from France were 0.33 and 0.31 (P=0.30), respectively. In the PEGASE study, the 825T allele frequency was 0.35 in female and male cases and 0.31 in male normotensive controls (P=0.12). The odds ratios for hypertension (PEGASE) and MI (ECTIM) associated with T-allele carrying were 1.23 (95% confidence interval, 0.94 to 1.62; P=0.13) and 1.11 (95% confidence interval, 0.88 to 1.39; P=0.37), respectively. There was no association of the GNB3 polymorphism with early onset of hypertension, familial history of hypertension, or blood pressure level. We conclude that the 825C/T polymorphism of the GNB3 gene did not contribute in any important way to the risk of essential hypertension or MI in these studies.     

ADD-1基因和GNB3基因多态性与原发性高血压的相关性研究

目的调查ADD-1基因和GNB3基因多态性与深圳地区原发性高血压的关系。方法用病例对照研究。高血压组97例,非高血压组87例。用MS-PCR和PCR-RFLP方法分别检测ADD-1基因G460T基因型及GNB3基因T825C基因型。结果①高血压组和非高血压组ADD-1基因型分别为GG0.237/0.241、GT0.505/0.460、TT0.258/0.299,差异无统计学意义(P=0.787);G等位基因频率为0.490/0.471,差异无统计学意义(P=0.724);②高血压组和非高血压组GNB3基因型分别为TT0.258/0.161、TC0.484/0.529、CC0.258/0.310,差异无统计学意义(P=0.265);T等位基因频率为0.5/0.425,差异无统计学意义(P=0.151);③联合基因分析高血压组TT CC联合基因型者显著少于非高血压组(P=0.043)。结论在深圳地区人群中,未发现ADD-1基因多态及GNB3基因多态与高血压相关,但两基因可能存在协同作用。     

WNK1基因单核苷酸多态性位点与高血压患者左心室质量指数的相关性研究

目的:探讨缺乏赖氨酸的丝氨酸/苏氨酸蛋白激酶1(WNK1)基因单核苷酸多态性位点rs956868与高血压患者左心室质量指数的相关性。方法:新发的轻中度原发性高血压患者121例,均来自北京市昌平地区的常住汉族人群,予以超声心动图检查,利用TaqMan MGB等位基因分型试剂盒检测患者WNK1基因多态性rs956868的分布频率。结果:rs956868位点(CA+AA)基因型患者的左心室质量指数显著高于CC基因型患者〔(86.46±26.35)vs.(77.16±20.64),P=0.046〕。用多元逐步回顾分析,校正年龄、性别、体质量指数、吸烟、饮酒、血压、血糖及血脂水平后,rs956868位点基因型仍与左心室质量指数具有相关性,它和性别、年龄、BMI一起与高血压患者左心室质量指数变异的34.3%有关(R2=0.343,P=0.026)。结论:WNK1基因单核苷酸多态性位点可能与高血压患者左心室肥厚的易感性有关。