妊娠高血压综合征亚甲基四氢叶酸还原酶基因和血管紧张素转换酶基因多态性研究

目的　探讨N5,N10 亚甲基四氢叶酸还原酶 (methyenetetrahydrofolatereductase ,MTH FR)基因和血管紧张素转换酶 (angiotensin convertionenzyme,ACE)基因多态性与妊娠高血压综合征的关系。　方法　应用多聚酶链反应 限制性内切酶片段长度多态性 (PCR RFLP)技术检测 6 2例妊娠高血压综合征 (妊高征组 )患者及 12 0例正常妊娠 (对照组 )的ACE和MTHFR基因多态性。　结果　妊高征组MTHFR基因T/T基因型频率 ( 2 7% )显著高于对照组 ( 15 % ) (P <0 .0 5 ) ,T等位基因频率 ( 5 2 % )也显著高于对照组 ( 39% ) (P <0 .0 1) ,妊高征组ACE基因缺失型纯合子 (DD)频率( 4 0 % )显著高于对照组的 ( 10 % ) (P <0 .0 1) ,缺失型 (D型 )等位基因频率 ( 6 0 % )显著高于对照组的( 2 9% ) (P <0 .0 1)。MTHFR基因T等位基因与ACE基因D等位基因之间存在协同作用。　结论　MTHFR基因和ACE基因多态与妊高征的发病有关 ,ACE基因与MTHFR基因之间可能有协同作用     

ACE和AGT基因多态性与子宫内膜异位症相关性的研究

目的:探讨ACE基因A240*T和AGT基因M235*T多态性与中国河北省汉族孕龄妇女Ⅲ、Ⅳ期EMs遗传易感性的关系。方法:用病例对照研究法,78例Ⅲ、Ⅳ期EMs患者与82例对照组的外周血白细胞为样本,用PCR-RFLP技术分析ACE基因A240*T和AGT基因M235*T多态性分布频率。结果:ACE基因的3种基因型AA、AT、TT在EMs组和对照组的分布频率分别为:41.0%、43.6%、15.4%;56.1%、39%、4.9%。A/T等位基因在两组的分布频率分别为62.8%、37.2%;75.6%、24.4%,两组差异有统计学意义(P<0.05)。AGT基因3种基因型MM、MT、TT在EMs和对照组的分布频率分别为6.4%、37.2%、56.4%;8.5%、35.4%、56.1%。M/T等位基因在两组的分布频率分别为25%、75%;26.2%、73.8%,两组差异无统计学意义。结论:携带ACE240*T等位基因增加患Ⅲ、Ⅳ期子宫内膜异位症的危险。AGT基因M235*TM/T等位基因在EMs组和对照组的分布无显著差异。     

血管紧张素转换酶基因多态性与妊高征的遗传易感性研究

目的 探讨血管紧张素转换酶(ACE）基因多态性与妊高征(PIH)的关系。方法 2000年5月至2003年5月，运用多聚酶链反应技术检测99例PIH及54例对照组的ACE基因多态性。结果 PIH患者ACE基因II、ID、DD基因型频率分别为20．2％、37．4％、42．4％，对照组II、ID、DD基因型频率分别为44．4％、29．6％、25．9％；两组的DD基因型及D等位基因频率比较差异有显著性意义；中、重型组DD基因型与轻型组相比差异有显著性。结论 ACE基因多态性与PIH的发病有关，且与PIH病情严重程度有关。     

妊高征与血管紧张素原基因M235T分子变异的关系

目的 :探讨中国成都地区人群中血管紧张素原 (AGT)基因 M2 35 T分子变异与妊娠高血压综合征 (PIH)的关系。方法 :采用聚合酶链反应及限制性片段长度多态性分析 ,对 6 0例 PIH患者和 6 0例正常孕妇进行 AGT基因 M2 35 T基因型及 T2 35等位基因检测。结果 :1在该研究的群体中未发现 AGT基因 2 35 TT型。 2 PIH患者 AGT基因 T2 35等位基因频率 (0 .4 6 )与对照组 (0 .4 3)相比无统计学差异 (P>0 .5 )。结论 :1AGT基因 M2 35 T分子变异与所研究人群 PIH的发生无关。 2 AGT基因 M2 35 T基因型和等位基因频率在不同人种和不同群体间是有差异的     

血管紧张素原基因变异与妊娠高血压综合征相关性探讨

目的 :探讨血管紧张素原 (AGT)基因M2 35T分子变异型与中国人妊娠高血压综合征发生的相关性。方法 :应用先进的聚合酶链 限制性片段多态长度分析 (PCR RELP) ,对 85例正常健康人 (对照组 )和 39例妊高征 (PIH)患者 (患病组其中有PIH家族史的 7例 )进行了AGT基因M2 35T变异型与PIH的相关性探讨。结果 :经 χ2 检验 ,患者组M 2 35T等位基因频率为 87.18%,对照组等位基因频率为 77.0 6 %,患者组与对照组等位基因频率差异无显著性 ;但在有家族史的 7例妊娠高血压综合征患者 ,其 2 35T等位基因频率为 10 0 %,对照组等位基因频率为 77.0 6 %,两者等位基因频率差异有显著性。结论 :血管紧张素原基因变异型M2 35T可能与有家族史的妊娠高血压综合征相关。     

ACE基因I/D多态性与子痫前期高血压和肾脏损害关系的研究

目的探讨血管紧张素转换酶（ACE）基因插入／缺失（I／D）多态性与子痫前期患者高血压和肾脏损害程度的相关性。方法选择子痫前期患者82例，正常孕妇45例，利用多聚酶链反应（PCR）分析其外周血白细胞中ACE基因多态性，计数两组孕妇ACE基因型和等位基因分布频率，比较不同基因型子痫前期患者高血压程度和肾功能。结果根据插入／缺失片段的有无，将ACE基因分为DD、ID、II三种基因型，子痫前期患者和正常孕妇ACE基因型和等位基因频率无统计学差异。子痫前期患者中携带D等位基因孕妇的收缩压和舒张压呈升高趋势，血清尿酸含量显著增加，但肌酐、尿素氮水平无统计学差异。结论ACE基因与子痫前期肾脏损害密切相关，携带D等位基因的子痫前期患者肾脏损害严重，血压也有升高趋势，提示D等位基因可能是子痫前期患者病情加重的不利因素。     

多囊卵巢综合征患者血管紧张素转换酶基因多态性与肾素血管紧张素系统关系的探讨

目的：探讨多囊卵巢综合征（PCOS）患者血管紧张素转换酶（ACE）基因多态性与肾素血管紧张素统（RAS）的关系，了解RAS在PCOS发病中的作用。方法：采用聚合酶链反应（PCR）方法，检测PCOS患者和对照组ACE基因插入和（或）缺失多态性；采用放射免疫方法测定两组血清醛固醇（ALD）水平，比较缺失型等位基因与ALD的关系。结果：PCOS患者ALD水平显著高于对照组，PCOS患者D等位基因组ALD水平显著高于Ⅰ等位基因组，结论：PCOS患者D等位基因的存在与RAS功能亢进有关，RASR的产物血管紧张素Ⅱ（ATⅡ）可使卵泡在各阶段闭锁，导致不排卵，参与了多囊卵巢和高雄激素血症的形成。     

血管紧张素Ⅰ转换酶基因和N5,N10-亚甲基四氢叶酸还原酶基因多态性与妊娠高血压综合征发病的关系

目的探讨血管紧张素Ⅰ转换酶(ACE)基因和N5,N10-亚甲基四氢叶酸还原酶(MTHFR)基因多态性与妊娠高血压综合征(妊高征)发病的关系.方法应用PCR技术检测99例妊高征患者(妊高征组,其中轻度21例、中度24例、重度54例)及54例正常孕妇(对照组)的ACE基因多态性,应用多聚酶链反应-限制性内切酶片段长度多态性(PCR-RFLP) 技术,检测两组孕妇的MTHFR基因多态性.结果妊高征组孕妇ACE基因Ⅱ、ID、DD基因型频率分别为20.2%、37.4%、42.4%,MTHFR基因CC、CT、TT基因型频率分别为53.5%、31.3%、15.2%.对照组孕妇ACE基因中Ⅱ、ID、DD基因型频率分别为44.4%、29.6%、25.9%, MTHFR基因CC、CT、TT基因型频率分别为46.3%、44.4%、9.3%,两组孕妇的DD、CT基因型及D等位基因频率比较,差异有显著性(P<0.05).妊高征组轻度与重度患者的DD和CT基因型比较,差异有显著性(P<0.05).回归分析表明,DD基因型、D等位基因与妊高征发病相关;CT基因型与重度妊高征相关.结论 (1)CC+DD基因型者易患妊高征;CC+Ⅱ或CT+Ⅱ基因型者不易患妊高征.(2)ACE基因中DD基因型、MTHFR基因中CT基因型是妊高征的易感基因,ACE基因中Ⅱ基因型是妊高征的保护基因.(3)ACE基因与MTHFR基因在妊高征发病中可能有协同作用.     

肾素-血管紧张素系统基因与妊娠高血压综合征的新进展

肾素-血管紧张素-醛固酮系统(renin-angiotensin system,RAS)基因是一种激素内分泌系统,在心血管功能调节、水盐平衡调节中起重要作用。RAS基因是妊高征主要的致病基因。AGT基因M235T多态、AT1R基因A1166C多态、ACE基因I/D缺失多态与妊高征的发病相关。     

血管紧张素转换酶基因与妊娠高血压综合征关系的探讨

目的　探讨血管紧张素转换酶（ACE）基因第16内含子中插入片段（insertion,I）和缺失片段（deletion,D）的多态性与妊娠高血压综合征（妊高征）的关系。方法　应用聚合酶链反应（PCR）技术检测60例妊高征患者（妊高征组）及50例正常孕妇（正常妊娠组）的ACE基因插入与缺失多态性。测定并比较妊高征组不同ACE基因类型者及正常妊娠组血管紧张素Ⅱ（AngⅡ）水平。结果　妊高征组ACE基因类型包括纯合插入型（II）、纯合缺失型（DD）、插入与缺失型（ID）。其基因频率依序排列为II（55.0%,33/60）>ID（26.7%,16/60）>DD（18.3%,11/60）。妊高征组DD者AngⅡ水平较正常妊娠组高;妊高征组II及ID者AngⅡ水平与正常妊娠组比较,差异无显著性(P>0.05)。结论　妊高征患者ACE基因的多态性可分为II、DD、ID。以II为主。DD妊高征患者伴有AngⅡ水平升高。妊高征是一种多基因决定和多种因素影响的疾病。     

Interaction between the polymorphisms of the renin-angiotensin system in preeclampsia

Preeclampsia is considered to be a multifactorial and multisystemic disorder with a genetic predisposition. Alterations in the renin-angiotensin system are considered to play a significant role in the pathogenesis of the disease. In order to investigate the possible association of the three most common polymorphisms of the renin-angiotensin system genes with preeclampsia we have examined 41 women with preeclampsia and 102 normotensive pregnant women. DNA samples were genotyped for the M235T polymorphism of the angiotensinogen gene (AGT), the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme gene (ACE) and the A1166C polymorphism of the angiotensin II type 1 receptor gene (AT1R) by PCR. Allele and genotype frequencies of the AGT gene polymorphism differed between the two study groups. The TT genotype of the M235T polymorphism was significantly increased in women who developed preeclampsia (P<0.02). In addition, women with preeclampsia and TT genotype had more frequently the DD genotype or the 1166C allele than the control group showing a significant interaction between the genes. In conclusion, we found an association between the angiotensinogen variant 235T and preeclampsia as well as an interaction between the variant 235T and the two other genes studied.     

Association of angiotensin-converting enzyme gene polymorphism with pregnancy-induced hypertension

BACKGROUND: To investigate the potential association of angiotensin-converting enzyme (ACE) gene polymorphism and serum ACE activity with pregnancy-induced hypertension (PIH). METHODS: The ACE genotype was identified and serum ACE activity was measured in 50 primigravidae with PIH and 50 normotensive primigravidae. These subjects were followed up to delivery and perinatal outcome noted. RESULTS: ACE DD genotype was found in 60% of subjects with PIH but only in 30% of normotensive subjects (P = 0.004). The odds ratio for developing hypertension in subjects with DD genotype was 3.5. The incidence of D allele of ACE gene was significantly higher in hypertensive subjects (0.74) than in normotensive subjects (0.56, P = 0.011). The odds ratio for developing hypertension in subjects with D allele was 2.24. However, the ACE genotype was similar in different categories of PIH and did not affect the perinatal outcome. The mean ACE activity in the hypertensive subjects (32.4 IU/l) and the normotensive subjects (23.7 IU/l) was similar (P = 0.092). The ACE activity did not differ significantly according to ACE genotype. CONCLUSIONS: We noticed an excess of DD genotype and D allele in ACE gene in PIH. However, this polymorphism does not correlate with the severity of hypertension or perinatal outcome. Serum ACE levels do not correlate with the ACE gene polymorphism or the development of PIH.     

Angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensin II type 1 receptor (AT1R) gene polymorphism and its association with preeclampsia in Chinese women.

OBJECTIVE: To investigate whether polymorphisms of angiotensin converting enzyme gene (ACE) and angiotensin II receptor type 1 gene (AT1R) are associated with etiology of preeclampsia and renal impact in women with preeclampsia. METHODS: DNA was extracted from peripheral blood of 133 patients with preeclampsia and 105 healthy pregnant women. The I/D polymorphism of the ACE gene was assessed by polymerase chain reaction, and the A1166C polymorphism of the AT(1)R gene was additionally assessed by DdeI digestion. The level of proteinuria, fasting serum urea, creatinine and uric acid were investigated according to different genotypes of ACE and AT1R genes. RESULTS: The frequency of genotypes of the ACE gene and the AT1R gene was similar in preeclampsia and normal pregnancy. DD and ID genotype predominated in patients with severe proteinuria, as well as increased serum urea and uric acid. Serum creatinine was also increased, but no significant difference was found among three genotypes. The level of proteinuria, serum uric acid, urea, and creatinine did not vary between different AT1R genotypes. Compared with patients without renal dysfunction, the frequency of DD and ID genotypes of ACE gene was much higher in those with renal dysfunction, but AC and CC genotypes of AT1R gene were not. CONCLUSION: We found no association of the two gene polymorphisms with preeclampsia. However, ACE gene I/D polymorphisms were associated with the severe proteinuria and renal dysfunction seen in preeclampsia. Preeclampsia patients carrying the D allele may be susceptible to renal dysfunction.     

妊高征孕妇血管紧张素转换基因的缺失多态性研究

目的探讨血管紧张素转换酶（ＡＣＥ）基因的缺失多态性与妊高征的关系。方法应用聚合酶链反应技术,检测３５例妊高征患者（观察组）及２５例正常孕妇（对照组）的ＡＣＥ基因中第１６内含子是否有Ａｌｕ重复结构存在。结果观察组的缺失型纯合子（ＤＤ型）ＡＣＥ基因占６５．７％,高于对照组的８．０％;观察组的缺失型（Ｄ型）ＡＣＥ等位基因出现频率为０．７６,高于对照组的０．２８。两组比较,差异有极显著性（Ｐ＜０．００１）。结论ＡＣＥ基因的缺失多态性可能与妊高征的发病有关。     

Angiotensin-Converting Enzyme Insertion/Deletion (ACE I/D) and Angiotensin II Type 1 Receptor (AT1R) Gene Polymorphism and Its Association with Preeclampsia in Chinese Women

Objective: To investigate whether polymorphisms of angiotensin converting enzyme gene (ACE) and angiotensin II receptor type 1 gene (AT1R) are associated with etiology of preeclampsia and renal impact in women with preeclampsia. Methods: DNA was extracted from peripheral blood of 133 patients with preeclampsia and 105 healthy pregnant women. The I/D polymorphism of the ACE gene was assessed by polymerase chain reaction, and the A1166C polymorphism of the AT₁R gene was additionally assessed by DdeI digestion. The level of proteinuria, fasting serum urea, creatinine and uric acid were investigated according to different genotypes of ACE and AT1R genes. Results: The frequency of genotypes of the ACE gene and the AT1R gene was similar in preeclampsia and normal pregnancy. DD and ID genotype predominated in patients with severe proteinuria, as well as increased serum urea and uric acid. Serum creatinine was also increased, but no significant difference was found among three genotypes. The level of proteinuria, serum uric acid, urea, and creatinine did not vary between different AT1R genotypes. Compared with patients without renal dysfunction, the frequency of DD and ID genotypes of ACE gene was much higher in those with renal dysfunction, but AC and CC genotypes of AT1R gene were not. Conclusion: We found no association of the two gene polymorphisms with preeclampsia. However, ACE gene I/D polymorphisms were associated with the severe proteinuria and renal dysfunction seen in preeclampsia. Preeclampsia patients carrying the D allele may be susceptible to renal dysfunction.     

Angiotensin converting enzyme gene insertion/deletion polymorphism in patients with polycystic ovary syndrome

Objective.?The aim of this study is to investigate the relevance of polymorphism in angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism to the pathophysiology of polycystic ovary syndrome (PCOS).

Subjects and methods.?Thirty patients with PCOS by Rotterdam consensus criteria and 33 control subjects were prospectively investigated. ACE gene amplification of DNA was performed by polymerase chain reaction. Homeostatic model assessment (HOMA-IR) was applied.

Results.?Compared to controls, ACE gene DD genotype and D allele were observed more frequently in PCOS (63% vs. 46% for DD genotype and 75% vs. 67% for D allele) (p?>?0.05). Body mass index, fasting glucose and insulin levels, HOMA-IR index and total testosterone levels were higher in PCOS group (p?<?0.05). The frequencies of D and I alleles were 45 (75%) and 15 (25%) for PCOS group and 44 (67%) and 22 (33%) for control group (p?>?0.05). No significant differences were observed in the genotype and allele distributions between cases and control groups. HOMA-IR index was significantly higher in patients with PCOS with DD genotype than those with II genotype (p?<?0.05).

Conclusion.?The ACE gene polymorphism was not associated with PCOS. However, the presence of D allele was associated with higher rate of insulin resistance in patients with PCOS.     

Angiotensin converting enzyme insertion/deletion polymorphism does not alter sepsis outcome in ventilated very low birth weight infants.

OBJECTIVE: This study compared the effect of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphisms on the incidence and outcome of sepsis in ventilated very low birth weight infants. STUDY DESIGN: Infectious complications were retrospectively determined in 295 (234 African-American, 58 Caucasian and three Hispanic) mechanically ventilated very low birth weight (VLBW) infants (<1500 g at birth) and compared ACE I/D genotype. RESULTS: The incidence of the D allele in the study population was 0.60. A total of 113 (38.3%) infants were homozygous DD, 128 (43.4%) were heterozygous ID and 54 (18.3%) were homozygous II. One or more episodes of late BSI developed in 28 (52%) of 54 infants with the II genotype, 66 (52%) of 128 infants with the ID genotype and 52 (46%) of 113 infants with the DD genotype (p=0.618). Neither the rates of non-CONS BSI (II: 24%, ID: 23%, DD: 22%; p=0.937) nor multiple bacteremic/fungemic episodes (II: 13%, ID: 16%, DD: 12%; p=0.641) were different between genotype groups. The ACE I/D polymorphism had no effect on sepsis-related mortality (II: 7%, ID: 5%, DD: 4%; p=0.692). Sepsis mortality for infants with late BSI was 14% in infants with the II genotype, 9% with the ID genotype and 10% with the DD genotype (p=0.764). CONCLUSIONS: The ACE I/D polymorphism does not have a significant effect on the incidence or outcome of sepsis in ventilated VLBW infants.     

Lack of association between angiotensin I-converting enzyme gene deletion polymorphism and cerebrovascular disease in Taiwanese.

BACKGROUND AND PURPOSE: Angiotensin I-converting enzyme (ACE) gene deletion polymorphism (D) has recently been suggested as a significant risk factor for cerebrovascular disease in studies involving Japanese and white populations. We investigated the role of ACE D polymorphism in the pathogenesis of cerebrovascular disease in Taiwanese. METHODS: To examine the association of ACE genotype and allele frequency with cerebrovascular disease, we conducted a study of 306 stroke patients and 300 control subjects matched by age and sex. RESULTS: Although the frequencies of both the homozygous deletion (DD) genotype and the D allele were greater in stroke patients than in control subjects, these differences were not significant. Further comparison of the frequencies of the DD genotype and the D allele in the three stroke subgroups (intracerebral hemorrhage, probable large-vessel disease, and probable small-vessel lacunar infarction) with the control group revealed no significant associations. Moreover, ACE gene polymorphism was not significantly associated with age of onset of stroke. Stepwise logistic regression analysis of the presence of the D allele and data on risk factors confirmed the lack of significant association between ACE deletion polymorphism and cerebrovascular disease. Moreover, no association was identified between ACE genotypes and any of the relative risk factors for cerebral infarction or severity of carotid atherosclerosis. CONCLUSIONS: Our results suggest that deletion polymorphism of the ACE gene is not associated with the pathogenesis of cerebrovascular disease in Taiwanese.