POLYMORPHISM OF ANGIOTENSIN I TYPE 1 RECEPTOR GENE IN ELDERLY PATIENTS WITH ESSENTIAL HYPERTENSION

Objective To detect the A/C1165 polymorphism of angiotensin Ⅱ type Ⅰ receptor (AT1-R)gene in essential hypertensive elderly. Methods The A/C1166 polymorphism of AT1-R gene was assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in a case-control study of 87 essential hypertensive elders (EH) and 55 normolensive elders (NT). Results The genotype frequencies of AA, AC, CC were 0 .805 , 0.161, 0 .034 in EH group and 0 .927 ,0 .073 ,0 .000 in NT group respectively. The frequency of C61166 allele was higher in EH group (0.115) than in NT group (0 .036 )(P<0 .05 ). Conclusion The resultsindicate that A/C1166 polymorphism of AT1-R gene may be associated with essential hypertension in elderly.     

Association of Polymorphisms in Angiotensin-converting Enzyme and Type 1 Angiotensin Ⅱ Receptor Genes with Coronary Heart Disease and the Severity of Coronary Artery Stenosis

To explore the relation of angiotensin-converting enzyme （ACE） and angiotensin Ⅱ type 1 receptor （AT1R） gene polymorphism with coronary heart disease （CHD） and the severity of coronary artery stenosis, 130 CHD patients who underwent coronary angiography were examined for the number of affected coronary vessels （≥75% stenosis） and coronary Jeopardy score. The insertion/deletion of ACE gene polymorphism and AT1R gene polymorphism （an A→C transversion at nucleotide position 1166） were detected by using polymerase chain reaction （PCR） and restriction fragment length polymorphism （RFLP） in CHD patients and 90 healthy serving as controls. The resuits showed that DD genotype and of ACE were more frequent in CHD patients than that in control group （38.5% vs 14.4%, P〈0.001）. The frequency of the ATIR A/C genotypes did not differ between the patients and the controls （10% vs 13.1%, P〉0.05）. The relative risk associated with the ACE-DD was increased by AT1R-AC genotype. Neither the number of affected coronary vessels nor the coronary score differed among the ACE I/D genotypes （P〉0.05）. But the number of affected coronary vessels and the coronary score were significantly greater in the patients with the AT1R-AC genotype than in those with the AA genotype （P〈0.05）. In conclusion, DD genotype may be risk factor for CHD and MI in Chinese people, and is not responsible for the development of the coronary artery stenosis. The AT1R-C allele may increase the relative risk associated with the ACE-DD genotype, and may be involved in the development of the stenosis of coronary artery.     

The Association between Polymorphism of TNF-α Gene and Hypertensive Disorder Complicating Pregnancy

To study whether the development of hypertensive disorder complicating pregnancy is associated with -308G→A, -850C→T mutation at promoter of TNF-α gene, the -308G→A, -850C→T polymorphism was examined in patients and healthy pregnant women by PCR-RFLP technique. The frequencies of genotype and allele were compared between the two groups. The re- sults showed that with -308G→A polymorphism distribution, the allele frequency of TNF2 and the frequency of the genotype TNF2/1 in the patient group was significantly higher in the patient group than in control group (P<0.05). A significant difference in genotype distribution of -850C→T poly- morphism was observed between the two groups. The allele frequencies of T in patient group was higher in the control group as compared with the patient group. The frequencies of CT and TT genotypes were lower in the patient group. It is concluded that the TNF2 allele of -308 is associated with the occurrence of hypertensive disorder complicating pregnancy, while T allele of -850 may be the protective factor against the development of the disease. TNF2/1 CC may be susceptibility genotype of hypertensive disorder complicating pregnancy.     

Gene polymorphism in apolipoprotein E and presenilin-1 in patients with late -onset Alzheimer’s disease

Objective To evaluate the association of apolipoprotein E (apoE) and presenilin-1 (PS-1) gene polymorphism with late-onset Alzheimer’s disease (AD). Methods A case-control study was undertaken to detect the polymorphism of apoE and PS-1 by polymerase chain reaction and digestion with the endonucleases of BspL Ⅰ, Hha Ⅰ and BamH Ⅰ. Results The frequencies of apoE ε3/4 genotype and ε4 allele in late-onset AD (n=42) were significantly higher than those of age-matched controls (P&lt;0.05). The frequencies of the apoE intron 1 enhancer (IE1) G/G genotype and G allele in late-onset AD were also significantly higher than those in controls (P&lt;0.05). The frequencies of the PS-1 1/1 genotype but not the 1 allele in AD were significantly higher than those in controls (P&lt;0.05).The apoE ε4 allele was associated with a tripling of risk for late-onset AD compared with that with no ε4 allele (odds ratio: 2.932). Homozygosity of the G allele in IE1 and 1/1 genotype in PS-1 was associated with a doubling of risk for late-onset AD, and odds ratios were 2.223 and 2.066, respectively.When the apoE ε4 was controlled, the association between the IE1 G/G genotype AD was no longer statistically significant (P&gt;0.05). We sequenced the exon 4 of apoE in patients with late-onset AD, and found no other genetic polymorphism or mutation except for apoE ε4 and IE1 G alleles associated with AD. Conclusion apoE ε4 gene appears to be the strongest gene risk factor for late-onset AD and its apparent association between the IE1 G/G genotype and late-onset AD is a consequence of the association between the ε4 and IE1 G/G genotype.The PS-1/1 genotype is weakly associated with late-onset AD.     

Association of polymorphisms in angiotensin II receptor genes with aldosterone-producing adenoma

This study examined the association of polymorphisms in angiotensinⅡreceptor genes(AT1R and AT2R) with the risk for aldosterone-producing adenoma(APA) in a Chinese Han population.Four polymorphisms including rs5182(573T/C) in exon 4,rs5186(1166A/C) in 3’-untranslated region(3’-UTR) in AT1R gene and rs5194(2274G/A) in 3’-UTR,rs1403543(1675G/A) in intron 1 in AT2R gene were detected in 148 APA patients and 192 normal subjects(serving as control) by using a MGB-Taqman probe.The distribution of genotypes of each locus was in accordance with Hardy-Weinberg Equilibrium(HWE) in the APA and control groups(P>0.05).The allele A frequency at rs5194 was significantly higher in the APA group(0.49) than in the control group(0.35)(χ2=12.08,P=0.001).Subjects with homozygotic genotype AA and heterozygotic genotype GA were at an increased risk for APA as compared to those with GG genotype(OR=2.66,95% CI=1.45-4.87;OR=1.67,95% CI=1.02-2.74).Furthermore,rs5194 single-nucleotide polymorphism(SNP) at AT2R gene was significantly associated with APA in additive(OR=1.64,95% CI=1.21-2.20,P=0.001),dominant(OR=1.94,95% CI=1.23-3.06,P=0.003),and recessive model(OR=2.01,95% CI=1.17-3.45,P=0.01).It was concluded that rs5194 polymorphism at AT2R gene was associated with the risk for APA,which may constitute a genetic marker of APA.     

Association of the apolipoprotein B gene polymorphisms with essential hypertension in Northern Chinese Han population

Objective To study the association of the apolipoprotein B gene polymorphisms with essential hypertension in Northern Chinese Han population. Methods XbaI and EcoRI polymorphisms of the apolipoprotein B (APOB) gene were genotyped by polymerase chain reaction (PCR) and restriction fragment-length polymorphism (RFLP) method in 503 unrelated hypertensive patients and 490 healthy controls recruited from international collaborative study of cardiovascular disease in Asia (InterAsia). Results The difference in the genotypic distributions could be neglected across the groups. The prevalence of X allele in healthy controls (4.8%) was less frequent in Chinese, and there was no significant difference in the frequency of the X allele between cases (5.7%) and controls (P=0.38). The observed E- allele frequencies were closely similar among groups (5.9% in cases vs 5.0% in controls, P=0.39). Logitstic regression analyses revealed that the lack of association still persisted after adjustment of other environmental factors. Haplotype analysis showed that X-E was most frequent and no haplotype could significantly contribute to essential hypertension. Conclusion The APOB gene XbaI and EcoRI polymorphisms are not associated with essential hypertension in the Northern Chinese Han population. Future studies on single nucleotide polymorphisms in larger samples are needed to further investigate the possible contribution of the APOB gene to essential hypertension.     

Polymorphism of the leptin gene promoter in pedigrees of type 2 diabetes mellitus in Chongqing, China

Background It has been shown that the presence of leptin is associated with deabefes, glucose wefabolism and insulin metablism. In this research, we evaluated the presence of the leptin C^-2549→A polymorphism in the Chinese population in Chongqing and verified its association with plasma leptin levels and anthropometric, metabolic, and clinical parameters.Methods Two hundred and sixty-nine patients with diabetes, 135 non-diabetic first-degree relatives of the patients, and 85 healthy controls were screened for the presence of C^-2549→A polymorphism using a PCR-RFLP assay. Body mass index, fasting leptin, fasting insulin, fasting glucose and homeostatic model assessment for insulin resistance ( HOMA)-IR were also determined.Results In the type 2 diabetes group, AA genotype frequency (6.32%) and A allele frequency(34.94%) was higher than in normal controls (1.18% and 25.29%, respectively). Diabetic patients with the AA genotype had lower fasting leptin and insulin levels than those with other genotypes.Carriers with the AC genotype had decreased fasting leptin and insulin levels and longer duration of disease as compared with those with CC genotype. The HOMA-IR of patients with AA or AC genotypes was lower than those with the CC genotype. In non-diabetic relatives group, individuals with the AA genotype had a lower fasting leptin level than those with the AC genotype. The fasting insulin and HOMA-IR level of carriers of the AA or AC genotype were lower than those of the CC genotype.Conclusion The C^-2549→A polymorphism in the leptin gene is associated with fasting leptin in patients with type 2 diabetes. The distribution of the genotypes in diabetic subjects from diabetic pedigrees differs from those in normal controls. The A allele frequency in diabetic patients is higher than that in normal controls. The haplotypes defined by genotypes are different in the familial subjects.     

Relationship between a novel polymorphism of lipoprotein lipase gene and coronary heart disease

Objective To investigate polymorphisms in the gene for lipoprotein lipase (LPL) in Chinese populations with coronary heart disease (CHD) and to inquire into the relationship between these polymorphisms in LPL gene and CHD. Methods Genomic DNA was extracted from patients with CHD and normal control subjects using a salting out method. The entire coding region and flanking sequences of all coding exons of the LPL gene were amplified by PCR technique and PCR products were detected by denaturing high- performance liquid chromatography (DHPLC) and sequenced with a dideoxy terminal termination method. Results A novel polymorphic site, G830A, that is within the fifth exon of the LPL gene was found. The 192 codon CGA was changed into CAA and resulted in the substitution of glutamine for arginine. Between the control and CHD groups, chi- square test showed no significant difference in the frequencies of the A/A genotype and A allele (P&gt;0.05). However, the frequencies of A/A genotype and A allele (0.653 and 0.786) in CHD patients with high plasma triglyceride/lowed plasma high density lipoprotein cholesterol were higher than those (0.415 and 0.642) in CHD patients without hyperlipidemia (P&lt;0.05). Conclusion No direct association was found between the LPL Arg192→Gln substitution polymorphism and CHD, but there is a significant positive correlation between the A/A genotype of the LPL gene and CHD associated with high triglyceride/lowed high density lipoprotein cholesterol. This study may provide new data for exploring the molecular mechanism of CHD.     

Osteopontin gene polymorphism in association with systemic lupus erythematosus in Chinese patients

Background Osteopontin (OPN) is one kind of cytokine which can play a number of roles in promoting activation of T lymphocyte, regulating balance between Th1 and Th2, participating in cell-induced immunologic response and stimulating B lymphocyte to express multi-clone antibodies. Some researches have showed that OPN may be involved in the pathogenesis of systemic lupus erythematosus (SLE). The aim of this study was to investigate possible association of a single nucleotide polymorphism（SNP）at position 9250 in exon 7 of the OPN gene (OPN gene 9250) with SLE in Chinese patients.Methods Totally 158 patients (18 males and 140 females) fulfilled the revised criteria for SLE by the American College of Rheumatology in 1982 and 180 healthy volunteer controls (34 males and 146 females), all from the south of China, consented to participate in the study. OPN gene 9250 polymorphism was detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).Results The frequency of TT genotype of the OPN gene 9250 was significantly lower (52.5% vs 70%, P&lt;0.05) and the frequency of TC genotype of the OPN gene 9250 was significantly higher (43.7% vs 29.4%, P&lt;0.05) in SLE patients than in controls. There were significant differences in OPN gene 9250 allele and phenotype frequencies between the SLE patients and controls (P&lt;0.05). When the SLE patients and controls were separated into men and women, significant differences of frequencies were noted in TT genotype, TC genotype and allele of the OPN gene 9250 in women (P&lt;0.05) but not in men (P&gt;0.05). Conclusions OPN gene 9250 polymorphism appears to be associated with susceptibility to SLE in Chinese Han ethnic population.     

The association analysis of FcεRⅠβ with allergic asthma in a Chinese population

Objective To investigate the link between the polymorphism of -109 and Glu237 in the high-affinity IgE receptor β （FcεRⅠβ） gene and susceptibilty to allergic asthma in a Chinese population.Method Blood samples from 216 allergic asthma patients and 198 age- and sex-matched controls were studied. A-109C/T and a coding variant Glu237Gly in FcεRⅠβ were detected with polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Results The genotype frequencies were 0.403 for -109T/T, 0.491 for －109T/C and 0.106 for －109C/C in allergic asthma in a Chinese population. No significant difference in the distribution of －109C/T polymorphism was found between allergic asthma subjects and healthy controls, however, homozygosity for the －109T allele was associated with increased total plasma IgE levels in subjects with allergic asthma (F=4.020,P&lt;0.05). The allele frequency of Gly237 in the patients and control was 0.236 and 0.136 respectively. There was a significant association between the Gly/Gly genotype and allergic asthma. Among allergic asthma patients Gly237 was significantly associated with high IgE levels.Conclusions These results suggest that the Gly237 variant of the FcεRⅠβ gene is involved in the development of allergic asthma. The-109C/T and Glu237Gly polymorphisms are two of the genetic factor identified thus far, which affect total plasma IgE levels of allergic asthma patients in a Chinese population.     

血管紧张素Ⅱ受体1基因多态性与原发性高血压的相关性研究

目的　本研究旨在观察中国汉族人血管紧张素Ⅱ受体 1基因多态性与原发性高血压的关系。方法　应用聚合酶链反应 限制性内切酶片段长度多态 (PCR RFLP)与电泳分型的方法检测 12 5例原发性高血压患者和 10 3例正常者AT1R基因 116 6位 (A116 6C)的多态性分布。结果　原发性高血压患者AT1R基因AC型频率比正常对照组高 (0 184vs 0 0 6 8,χ2 =6 6 5 4 ,P <0 0 5 ) ,C116 6等位基因频率原发性高血压组高于正常对照组 (0 0 92vs 0 0 34,χ2 =6 186 ,P <0 0 5 )。结论　在中国汉族人群中 ,AC基因型与原发性高血压有关 ,C等位基因可能是高血压的易感基因。     

POLYMORPHISM OF ANGIOTENSIN Ⅱ TYPE 1 RECEPTOR GENE IN ELDERLY PATIENTS WITH ESSENTIAL HYPERTENSION

Objective To detect the A/C1166 polymorphism of angiotensin Ⅱ type-1 receptor (AT1 R) gene in essential hypertensive elderly.MethodsThe A/C1166 polymorphism of AT1 R gene was assessed by polymerase chain reaction restriction fragment length polymorphism (PCR RFLP) in a case control study of 87 essential hypertensive elders (EH) and 55 normotensive elders (NT).ResultsThe genotype frequencies of AA, AC, CC were 0.805, 0.161, 0.034 in EH group and 0.927, 0.073, 0.000 in NT group respectively. The frequency of C1166 allele was higher in EH group (0.115) than in NT group (0.036)(P＜0.05).ConclusionThe results indicate that A/C1166 polymorphism of AT1 R gene may be associated with essential hypertension in elderly.     

血管紧张素Ⅱ—1型受体基因多态性与老年原发性高血压水平的关系

目的研究血管紧张素Ⅱ-1型受体(ATl-R)基因A/C1166多态性与老年原发性高血压(EH)血压水平的关系。方法应用PCR-RFLP技术检测87例老年EH患者和55例正常老年人的AT1-R基因A/C     

老年原发性高血压AT1一R基因多态性的研究

目的 研究老年原发性高血压(EH)血管紧张素Ⅱ型受体(AT1一R)基因A／C1166多态性的特征。方法 应用聚合酶链反应一限制性片段长度多态性(PCR—RFLP)技术检测87例汉族老年EH患者和55例正常老年人的AT1－R基因A/C1166多态性分布。结果87例老年EH患者的C1166等位基因频率为0．115,55例正常老年人为0．036,经统计学分析两组间有显著差异(P<0．05)。结论老年EH的患者C1166等位基因频率明显升高,可能为EH发病的危险因素。     

原发性高血压患者血管紧张素Ⅱ-1型受体基因多态性

目的研究血管紧张素Ⅱ-1型受体基因多态位点A1166C与原发性高血压的关系。方法采用聚合酶链反应技术（PCR）对48名40岁以上成人和39例原发性高血压患者血管紧张素Ⅱ-1型受体（AT1R）基因多态性进行检测。结果 AC基因型、C等位基因频率高血压组与健康人群对照组差别无统计学意义（χ2=0.026、0.023,P〉0.05）。结论血管紧张素Ⅱ-1型受体基因可能与原发性高血压发病无关。     

1型血管紧张素Ⅱ受体基因多态性与2型糖尿病伴高血压的相关性

目的：探讨1型血管紧张素Ⅱ受体（AT1R）基因多态性与2型糖悄病伴高血压之间的相互关系。方法：以AT1R基因为候选基因，应用PCR方法，检测132例2型糖尿病伴高血压患者及107例2型糖尿病无高血压患者的AT1R基因多态性。结果：2组研究对象AA基因型分布频率分别为88．79％与96．97％，AC基因型分布频率分别为11．21％与3．03％，A等位基因携带率分别为94．39％与98．48％，C等位基因携带率分别为5．61％与1．52％，均有显著性差异（P＜0．05），提示AT1R基因多态性与2型糖尿病伴高血压的发生有相关性，且糖尿病伴高血压患者病程显著延长，正常血压糖尿病患者与单纯舒张压升高糖尿病患者之间AT1R－A1166－C基因多态性无显著差异，而与单纯收缩压升高糖尿病患者之间有显著性差异，结论：AT1R基因参与型糖悄病伴高血压的发病，并仅与收缩压升高有关。     

血管紧张素Ⅱ1型受体基因多态性与宁夏回族原发性高血压的相关性研究

目的研究宁夏地区回族人群原发性高血压(essential hypertension,EH)与血管紧张素Ⅱ1型受体(angiogen-esisⅡtype 1,AT1R)基因A1166C多态性的关系。方法采用病例-对照研究方法,选取宁夏地区回族146例原发性高血压患者和112例正常血压者分别作为病例组(EH组)和对照组,应用多聚酶链式反应(polymerase chain reaction,PCR)结合限制性片段长度多态性(restriction fragment length polymorphism,RFLP)方法对以上人群的外周血白细胞DNA进行AT1R(A1166C)的基因多态性检测,分析该位点不同基因型及等位基因频率在EH组和对照组中的分布。结果 EH组AA和AC基因型分布频率为88.36%和11.64%,对照组中分别为93.75%和6.25%,两组相比差异无统计学意义(P>0.05),未发现CC基因型;A1166与1166C等位基因频率在EH组中分别为94.18%、5.82%,在对照组中分别为96.87%和3.13%,两组相比差异也无统计学意义(P>0.05)。EH组和对照组不同性别间上述基因型的分布及等位基因频率差异亦无统计学意义(P>0.05)。结论 AT1R基因A1166C多态位点分子变异与宁夏回族原发性高血压患者易感无明显相关性。     

AT1R基因A1166C多态性与新疆维吾尔族人群原发性高血压的关系

目的：探讨血管紧张素Ⅱ1型受体(AT1R)基因A1166C多态性与维吾尔族人群原发性高血压
(EH)的关系,阐述AT1R基因A1166C在EH中的作用机制。方法：收集EH组167例、对照组469例、共
636例维吾尔族人群血液样本,采用聚合酶链式反应-限制性片段长度多态性技术（PCR-RFLP）对AT1R基因A1166C进行多态性检测,分析AA、AC和CC 3种基因型以及该位点A、C不同等位基因频率在EH组和对照组中的分布。结果：EH组AC+CC基因型和C等位基因频率明显高于对照
组,差异有统计学意义（χ2=10.179 ,P=0.001）;AC+CC基因型人群患EH的危险度是AA基因型人群的1.6倍（OR=1.612,95%CI:1.191~2.183）。结论：AT1R基因A1166C多态性与维吾尔族EH的发病可能存在一定关联。
［关键词］［中图分类号］     

血管紧张素Ⅱ-1型受体基因A1166→C多态性与冠心病关联的研究

目的探讨血管紧张素Ⅱ-1型受体(AT1R)基因A1166→C多态性与冠心病的关系. 方法应用多聚酶链反应(PCR)对成都地区汉族133例正常对照及113例冠心病患者(其中52例伴有高血压)的AT1R基因A1166→C多态性进行分析.结果冠心病患者的C等位基因频率与正常对照组比较无显著性差异(0.066 vs 0.075, P>0.05).冠心病伴有高血压组的C等位基因频率与未伴有高血压组的C等位基因频率比较,有降低趋势(0.038 vs 0.090,P=0.09).冠心病伴有高血压组与正常对照组比较,C等位基因频率也有降低趋势(0.038 vs 0.075,P=0.14).结论 AT1R基因A1166→C多态性与冠心病无关联, AT1R基因A1166→C多态性与原发性高血压的发生可能有一定关联.     

血管紧张素Ⅱ-2型受体与原发性高血压的相关性研究

目的:研究血管紧张素Ⅱ-2型受体(AngiogenesisⅡtype2,AT2R)基因C3123A多态性与宁夏地区汉族人群原发性高血压(Essential hypertension,EH)的关系。方法:选择原发性高血压患者137例和正常血压者149例分别作为病例组(EH组)和对照组(NT组),应用聚合酶链反应—限制性片段长度多态性(PCR-RFLP)技术检测AT2R基因多态性。结果:女亚组:EH组CC、AC、AA基因型频率和等位基因频率与正常对照组相比,差异无统计学意义(P>0.05);男亚组:等位基因频率与正常对照组相比,差异无统计学意义(P>0.05)。女亚组中AC+AA基因型组平均动脉压高于CC基因型组,差异有统计学意义(P<0.05),余临床资料差异无统计学意义(P>0.05),男亚组中,不同基因型间临床资料差异无统计学意义(P>0.05)。二元逐步logistic回归显示女亚组中BMI、CR、GLU、AA+AC型基因组为危险因素,男亚组中BMI为危险因素。结论:AT2R基因C3123A多态位点分子变异与宁夏汉族原发性高血压患者易感无明显相关性。