血管紧张素原基因M235T多态性与肥厚型心肌病的关系

目的　探讨血管紧张素原 ( angiotensinogen,AGT)基因 M2 35 T变异与肥厚型心肌病( hypertrophic cardiomyopathy,HCM)的关系。方法　对 72例 HCM患者与 80名正常对照者进行病例 -对照研究。采用聚合酶链反应与限制性片段长度多态性技术检测 AGT基因 M2 35 T变异。同时通过 M型二维超声心动图分别测量室间隔、左室后壁和心尖部心肌厚度。结果　 ( 1)经 PCR扩增及 Tth111 酶切 ,AGT基因型有 3种形式 :MM、TT与 MT基因型。两组 AGT基因型的分布均符合 Hardy- Weinberg平衡。 ( 2 )AGT基因 M2 35 T基因型在 HCM组与对照组的分布差异有显著性 ( χ2 =6 .0 90 ,P<0 .0 5 )。HCM组 TT基因型与 T2 35等位基因的频率均高于对照组 ( TT基因型 :0 .6 3vs0 .4 5 ,OR=2 .0 37,95 % CI:1.0 6 4～7.899,P<0 .0 5 ;T2 35等位基因 :0 .78vs0 .6 4 ,OR=1.990 ,95 % CI:1.197～ 3.30 8,P<0 .0 1)。 ( 3) HCM组TT基因型患者左室壁最厚处平均厚度明显大于 MM、MT基因型患者 [( 19.1± 4 .8) mm vs( 15 .3± 2 .6 )mm与 ( 16 .2± 5 .1) mm,F=4 .2 6 1,P<0 .0 5 ]。结论　 AGT基因 M2 35 T变异与 HCM的发病显著相关 ,TT基因型或 T2 35等位基因可能是参与 HCM发生及加重心肌肥厚的一个遗传方面的危险因素     

Sequence variants of ACE, AGT, AT1R, and PAI-1 as genetic risk factors for vascular dementia

Sequence variants of angiotensin converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen (AGT) T235M, angiotensin II type 1 receptor (AT1R) A1166C, and plasminogen activator inhibitor-1 (PAI-1) 4G/5G were analyzed to see their genetic associations with vascular dementia as its candidate genetic risk factors involving renin-angiotensin and fibrin systems. While the ACE I/D, AT1R A1166C, and PAI-1 4G/5G did not contribute to the genetic susceptibility to vascular dementia (P>0.05), a significant association with vascular dementia was shown in the T235M polymorphism of AGT. The frequency of the M allele in patients was higher than in controls with the odds ratio (OR) estimate of 1.51 (P<0.05). In a dominant model, the TM+MM genotypes increased the risk of vascular dementia compared to the TT genotype (OR=2.01; P<0.001). The current results suggested that AGT T235M polymorphism might be a risk factor of vascular dementia.     

血管紧张素原、血管紧张素Ⅱ一型受体基因多态性与原发性高血压的相关性研究

目的 :探讨血管紧张素原AGT(M2 3 5T)、血管紧张素Ⅱ一型受体AT1 R(A1166C)基因多态性与中国四川籍人群原发性高血压(EH)的关系。方法 :采用聚合酶链反应 (PCR)及限制性片段长度多态性分析 (RFLP)方法分析人类白细胞染色体DNA中AGT、AT1 R基因多态性。结果 :12 2例EH病例组与 87例正常对照组AGT等位基因频率T、M分别为 :T :0 .82 8vs 0 .661,M :0 .172vs 0 .3 3 9。AT1 R等位基因频率A、C分别为 :A :0 .968vs 0 .989,C :0 .0 3 2vs 0 .0 11。各基因型频率及等位基因频率符合Hardy Weinberg平衡定律。EH病例组AGT基因T等位基因频率和TT型明显高于对照组(χ2 =11.7,P <0 .0 1和 χ2 =15 .6,P <0 .0 1)。结论 :AGT基因多态性与EH密切相关 ;而AT1 R基因多态性与EH无关。     

肾素-血管紧张素系统基因多态性与糖尿病及合并肾病的关系

目的探讨血管紧张素I转换酶(ACE)基因及血管紧张素原(AGT)基因与2型糖尿病(DM)及合并糖尿病肾病(DN)的相关性。方法分别用PCR、突变基因分离聚合酶链反应(MS-PCR)技术对195例2型DM患者和136例正常对照者的ACEI/D与AGTM235T多态性进行检测。结果(1)DM组ACE-DD基因型和D等位基因频率均比对照组显著增高(P<0.001)。(2)DN(+)组ACE基因型和等位基因频率与DN(-)组比较无显著性差异。(3)AGT基因型分布与等位基因频率在3组中均无显著性差异。(4)联合分析ACE-DD型及AGT-TT型对DN(+)、DN(-)的OR分别为4.17和3.16;均高于单基因DD型及TT型的OR值。结论(1)ACEDD基因型和D等位基因可能是广西地区人群2型DM的易感因素。(2)未发现ACEI/D或AGTM235T多态性单一因素与2型DM患者中DN的发生有关联。(3)ACE-DD基因型与AGTM235T-TT基因型在2型DM及DN发生中有协同作用。     

血管紧张素原基因M235T分子变异与心肌梗塞的关系

目的为探讨血管紧张素原（ＡＧＴ）基因Ｍ２３５Ｔ分子变异与心肌梗塞（ＭＩ）的关系。方法采用聚合酶链反应、限制性片段长度多态性分析，对５７例ＭＩ患者和７６例无冠心病证据的对照组进行ＡＧＴ基因Ｍ２３５Ｔ等位基因检测。结果ＭＩ患者ＡＧＴ基因２３５ＴＴ型（０．７０）和Ｔ２３５等位基因（０．８２）的频率显著高于对照组（分别为０．４２和０．６３，Ｐ＝０．０１３和Ｐ＜０．０２５）。经校正冠心病的主要危险因素后，ＡＧＴ基因２３５ＴＴ型仍可显著增加心肌梗塞发生的危险性（比数比３．６５，Ｐ＝０．０１６）。结论ＡＧＴ基因２３５ＴＴ型可能是中国人群ＭＩ发病的重要危险因素之一。     

Angiotensinogen M235T polymorphism and the risk of myocardial infarction and stroke among hypertensive patients on ACE-inhibitors or beta-blockers

Angiotensinogen is an essential component of the renin-angiotensin system. ACE-inhibitors and beta-blockers both have a direct influence on this system. To investigate whether the association between use of ACE-inhibitors or beta-blockers and the risk of myocardial infarction (MI) or stroke is modified by the T-allele of the angiotensinogen M235T polymorphism. In this study, 4097 subjects with hypertension , aged 55 years and older, were included from the Rotterdam Study, a population-based prospective cohort study in The Netherlands, from July 1, 1991 onwards. Follow-up ended at the diagnosis date of MI, stroke, death, or the end of the study period (January 1, 2002). The drug-gene interaction on the risk of MI or stroke was determined with a Cox proportional hazard model with adjustments for each drug class as time-dependent covariates. The risk of MI was increased in current use of ACE-inhibitors with the MT or TT genotype compared to ACE-inhibitors with the MM genotype (Synergy Index (SI): 4.00; 95% CI: 1.32-12.11). A significant drug-gene interaction was not found on the risk of stroke (SI: 1.83; 95% CI: 0.95-3.54) in ACE-inhibitor users or between current use of beta-blockers and the AGT M235T polymorphism on the risk of MI or stroke. ACE-inhibitor users with at least one copy of the 235T-allele of the AGT gene might have an increased risk of MI and stroke.     

血管紧张素原基因M235T分子变异与2型糖尿病肾病的关系

目的　探讨血管紧张素原（ａｎｇｉｏｔｅｎｓｉｎｏｇｅｎ , Ａ Ｇ Ｔ） 基因 Ｍ２３５ Ｔ 分子变异与中国人无肾病并发症的２ 型糖尿病（ｄｉａｂｅｔｅｓ ｍ ｅｌｌｉｔｕｓ , Ｄ Ｍ） 、２ 型糖尿病肾病（ｄｉａｂｅｔｉｃ ｎｅｐｈｒｏｐａｔｈｙ , Ｄ Ｎ） 的关系。方法　用 Ｐ Ｃ Ｒ及 Ｒ Ｆ Ｌ Ｐ 方法对８４ 例 Ｄ Ｍ、９６ 例 Ｄ Ｎ 及９８ 名正常对照进行了 Ａ Ｇ Ｔ 基因 Ｍ２３５ Ｔ 多态性的检测。结果　 Ｄ Ｎ 组 Ｔ 等位基因频率０８２ , Ｔ Ｔ 基因型频率０７０ ,与对照组（０６３ ,０４３） 比较有显著差异（ Ｐ＝ ０００３ , Ｐ＝００００４） ;校正了 Ｄ Ｎ 的几种危险因素后, Ｔ Ｔ 基因型对 Ｄ Ｎ 的 Ｏ Ｒ 为３４７（９５ ％ Ｃ Ｉ 为１５１ ～７９４ , Ｐ＝０００３３） 。 Ｄ Ｍ 组基因型频率分布与对照组比较无显著差异（ Ｐ＞ ００５） 。结论　 Ａ Ｇ Ｔ 基因 Ｔ Ｔ 型可能是中国人群２ 型糖尿病肾病的独立危险因素之一。     

血管紧张素原基因M235T分子变异与型糖尿病肾病的关系

目的 探讨血管紧张素原ａｎｇｉｏｔｅｎｓｉｎｏｇｅｎ,ＡＧＴ）基因Ｍ２３５Ｔ分子变异与中国人无肾病并发症的２型糖尿病（ｄｉａｂｅｔｅｓ ｍｅｌｌｉｔｕｓ,ＤＭ）、２型糖尿病肾病（ｄｉａｂｅｔｉｃ ｎｅｐｈｒｏｐａｔｈｙ,ＤＮ）的关系。方法用ＰＣＲ及ＲＦＬＰ方法对８４例ＤＭ、９６例ＤＮ及９８名正常对照进行了ＡＧＴ基因Ｍ２３５Ｔ多态性的检测。结果 ＤＮ组Ｔ等位基因频率０．８２,ＴＴ基因型频率０．７０     

AGT基因T174M多态性与新疆哈萨克族人高血压相关性分析

目的了解AGT基因T174M多态性在新疆哈萨克族人群中分布特点,以探索影响哈萨克族人AGT基因T174M变异的因素和T174M变异与高血压的关系。方法采用随机入选的方法,选择年龄在30岁以上哈萨克族牧民669人作为研究对象。提取入选人群白细胞基因组DNA,采用PCR、RFLP分子生物技术检测AGT基因第二外显子T174M多态位点等位基因、基因型频率,比较不同分组人群频率的差异。结果研究人群T174M位点等位基因、基因型分布频率分别为0.87、0.13(T,M)和0.76、0.24(TT,TM+MM);AGT基因T174M多态位点等位基因及基因型分布频率在哈萨克族男、女人群组分别为0.86、0.14和0.89、0.11(T,M);0.73、0.27和0.78、0.22(TT,TM+MM),均无统计学差异(P>0.05);分析T174M多态位点等位基因及基因型分布频率随年龄变化的趋势,未发现频率在各年龄段的分布差异(P>0.05);T174M多态位点等位基因、基因型频率在不同血压组人群的分布不存在显著性差异(P>0.05);结论年龄、性别不影响哈萨克族人AGT基因T174M的变异,而AGT基因T174M变异可能与哈萨克族人高血压的发病无关。     

Meta-Analysis of Adiponectin Polymorphisms and Colorectal Cancer Risk

Objective The adiponectin gene (ADIPOQ) has been suggested to be associated with the pathogenesis of colorectal cancer (CRC). However, the results have been inconsistent. In this study, we performed a meta-analysis to investigate the association between adiponectin polymorphisms and CRC risk.Methods All eligible case-control studies published up to March 2013 were identified by searching PubMed, Web of Science and CNKI. Effect sizes of odds ratio (OR) and 95% confidence interval (95% CI) were calculated by using a fixed- or random-effect model.Results A total of 9 case-control studies were included, Of those studies, there were eight studies (2024 cases and 2777 controls) for rs1501299G/T polymorphism, five studies (1401 cases and 1691 controls) for rs2241766T/G polymorphism, five studies (2945 cases and 3361 controls) for rs266729C/G polymorphism, three studies (1221 cases and 1579 controls) for rs822395A/C polymorphism and three studies (1222 cases and 1575 controls) for rs822396A/G polymorphism. Overall, a significant association was observed for rs2241766T/G polymorphism under heterozygote comparison (TG vs. TT: OR=1.22, 95%CI: 1.05-1.43); while there was no significant association for rs2241766 polymorphism under other genetic models, and for other four polymorphisms under all genetic models. Besides, when stratified analyses by ethnicity, no significant association between five polymorphisms and CRC risk were observed under all genetic models among Asian, Caucasian and African-American.Conclusions This meta-analysis indicated that adiponectin rs2241766T/G rather than rs1501299G/T, rs266729C/G, rs822395A/C and rs822396A/G polymorphism was associated with the risk of colorectal cancer.     

AGT、ACE基因多态性与成人过敏性紫癜和过敏性紫癜性肾炎的相关性

目的探讨肾素-血管紧张素系统中AGT基因M235T和ACE基因I／D多态性与过敏性紫癜和过敏性紫癜性肾炎易感性的关系。方法应用PCR和PCR—RFLP技术检测145例过敏性紫癜／过敏性紫癜性肾炎患者与172例正常对照组血管紧张素原基因第2外显子M235T多态性及血管紧张素转换酶基因第16内含子I／D多态性。结果①AGT基因型构成比在HSP组、HSPN组与正常对照组之间差异有统计学意义（P=0．008,P=0．002）,但在HSP和HSPN之间差异无统计学意义（P=0．180）。AGT—TT基因型和丁等位基因携带者具有较高的患HSP、HSPN的风险。②ACE基因型构成比在HSPN组与正常对照组之间差异有统计学意义（P=0．003）,但在HSP和正常对照组、HSP和HSPN之间差异无统计学意义（P=0．065,P=0．073）。ACE—DD基因型和D等位基因携带者具有较高的患HSPN的风险。结论携带AGT基因M235T多态性增加患HSP／HSPN的风险,携带ACE基因I／D多态性增加患HSPN的风险。     

Association of the Vascular Endothelial Growth Factor Gene Polymorphisms (–460C/T, +405G/C and +936T/C) with Endometriosis: A Meta‐Analysis

Published data on the association between the vascular endothelial growth factor (VEGF) gene –460C/T (rs833061), +405G/C (rs2010963), +936T/C (rs3025039) polymorphisms and endometriosis risk are inconclusive. Eleven eligible case‐control studies including 2690 cases and 2803 controls were included in this meta‐analysis through searching the databases of PubMed and CBMdisc (up to August 1, 2011). In the overall analysis, no significant association between the –460C/T and +405G/C polymorphisms and risk of endometriosis was observed. However, significant associations were observed between endometriosis risk and VEGF+936T polymorphism with summarized odds ratio of 1.19 (95%CI, 1.02–1.37), 1.18 (95%CI, 1.03–1.37), 1.15 (95%CI, 1.01–1.30) for CT versus CC genotype, dominant mode (CT/TT vs. CC) and allele comparison (T vs. C), respectively. Furthermore, stratified analysis showed that significantly strong association between +936T/C polymorphism and endometriosis was present only in stage III–IV (OR = 1.32 for dominant mode; OR = 1.30 for T vs. C), but not in stage I–II. However, no significantly increased risk of endometriosis was found in any of the genetic models in Asians or in Caucasians. This meta‐analysis supports that VEGF+936T/C polymorphism is capable of causing endometriosis susceptibility.     

Relationship of polymorphisms in the renin-angiotensin system and in E-selectin of patients with early severe coronary heart disease

 Previous association studies between angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) polymorphisms and several cardiovascular diseases have reported variable results. Therefore we examined the association of the DNA variants of ACE and AGT with early, severe coronary heart disease (CHD). In addition, we compared the genotypes of both polymorphisms and the recently discovered polymorphism in the E-selectin gene in both patients and an unselected population. This study included 113 patients with severe CHD (50 years old or less) and up to 197 control subjects. The frequencies of the ACE I/D variants were 48% I and 52% D in the controls and 46% I and 54% D in the patients. The frequencies of the AGT-M235T polymorphism were 60.8% M and 39.2% T in controls and 49.1% M and 50.9% T in the patients. The frequencies of the S128R polymorphism of the E-selectin were 91.3% S and 8.7% R in controls and 84.5% S and 15.5% R in the patients. In our studies the DD genotype of ACE was not associated with early severe CHD. We found a correlation between the M235T molecular variant of AGT and the S128R variant of E-selectin to early severe CHD. Received: 15 February 1996 / Accepted: 2 October 1996     

血管紧张素转换酶和血管紧张素原基因多态性及其与青海妊娠高血压疾病的相关性

目的探讨血管紧张素转换酶(ACE)和血管紧张素原(AGT)基因表达、基因多态性与青海孕产妇妊娠高血压疾病的相关性。方法选择210例妊娠高血压患者(HDCP组)和220例正常孕妇(CK组),运用限制性内切酶片段长度多态性聚合酶链反应(PCR-RFLP)方法检测AGT M235T、ACE I/D基因多态性。结果CK组ACE基因DD、ID、Ⅱ所占比例分别为28.18%、47.73%、24.09%,HDCP组分别为33.81%、51.90%、14.29%(P<0.05,故两组的ACE基因分布有差异),HDCP组和对照组ACE I/D多态性等位基因I和D频率分布有差异(P<0.05),HDCP组D等位基因频率高于对照组(χ^2=5.188,P<0.05),ACE基因型分布符合Hardy-Weinberg遗传平衡(χ^2=0.423,df=2,查表χ^2界值表,P>0.05,达到遗传平衡);CK组AGT基因MM、MT、TT所占比例分别为24.09%、43.64%、32.27%,HDCP组分别为15.71%、42.86%、41.43%(P<0.05,故两组的AGT基因分布差异有统计学意义),HDCP组和对照组AGT M235T多态性等位基因M和T频率分布有差异性(P<0.05),HDCP组T等位基因频率高于对照组(χ^2=6.796,P<0.05),AGT基因型分布符合Hardy-Weinberg遗传平衡(χ^2=3.242,df=2,查表χ^2界值表,P>0.05,达到遗传平衡)。结论ACE I/D多态性和AGT M235T多态性与青海省汉族妊娠期高血压疾病有关,D等位基因和T等位基因可能是妊娠高血压疾病的易感基因。     

Angiotensinogen and angiotensin II type 1 receptor gene polymorphism in patients with autosomal dominant polycystic kidney disease: effect on hypertension and ESRD

Autosomal dominant polycystic kidney disease (ADPKD), a common genetic disease, is characterized by the development of hypertension and end stage renal disease. An increase in the activity of the renin-angiotensin system, due to a renal ischemia caused by cyst expansion, contributes to the development of hypertension and renal failure in ADPKD. Recently, the angiotensinogen (AGT) gene, M235T, and angiotensin II type 1 receptor (ATR) gene, A1166C, polymorphisms have been associated with the susceptibility to develop hypertension and renal disease. We hypothesized that the AGT M235T and ATR A1166C polymorphisms could account for some of the variability in the progression of ADPKD. Genotyping was performed in 108 adult patients with ADPKD, and 105 normotensive healthy controls, using PCR and restriction digestion. We analyzed the effects of the AGT M235T and ATR A1166C polymorphisms on hypertension and age at the end stage renal disease (ESRD). Of the 108 patients with ADPKD, 64 (59%) had hypertension and 24 (22%) reached the ESRD. The prevalence of hypertension were; [MM+MT], [TT] genotypes, 60%, 59% (p=1.00); [AA], [AC+CC] genotypes, 60%, 50% respectively (p=0.54). The ages at the onset of ESRD were; [MM+MT], [TT] genotypes, 50 +/- 9 years, 56 +/- 8 years (p=0.07); [AA], [AC+CC] genotypes, 54 +/- 8 years, 52 +/- 14 years, respectively (p=0.07). There were no differences in the prevalence of hypertension and the ages at the ESRD in relation to the AGT M235T and ATR A1166C polymorphisms. We suggest that the AGT and ATR gene polymorphisms would not have an effect on hypertension or the ESRD in ADPKD.     

Lack of an association between Paraoxonase 1 gene polymorphisms (Q192R, L55M) and Alzheimer's disease: a meta-analysis

The association between Paraoxonase 1 (PON1) gene polymorphisms (Q192R, L55M) and Alzheimer's disease (AD) risk has been reported inconsistent results. To assess the association between PON1 polymorphisms and AD risk, a meta-analysis was performed. Based on comprehensive searches of the PubMed, Embase, Web of Science, Weipu, and CBM databases, a total of 10 studies including 3081 AD cases and 3054 controls were identified. The pooled odds ratio (OR) with 95% confidence interval (95% CI) were performed. There was no significant association between PON1 Q192R polymorphism and AD risk in all comparison models (R vs. Q, OR=0.89, 95% CI=0.82-0.96; RR vs. QQ, OR=0.83, 95% CI=0.68-1.01; RR+RQ vs. QQ, OR=0.86, 95% CI=0.75-0.97; and RR vs. QR+QQ, OR=0.94, 95% CI=0.81-1.11). For the PON1 L55M polymorphism, lack of an association was also found (L vs. M, OR=0.95, 95% CI=0.86-1.05; LL vs. MM, OR=0.67, 95% CI=0.51-0.88; LL vs. ML+MM, OR=0.82, 95% CI=0.69-0.98; and LL+ML vs. MM, OR=0.75, 95% CI=0.58-0.96). On subgroup analysis by ethnicity, similar results were found. Conclusively, the present meta-analysis revealed that PON1 gene polymorphisms (Q192R, L55M) were unlikely to contribute to AD susceptibility.     

血管紧张素原基因单倍型与原发性高血压的关联研究

目的 研究中国人血管紧张素原（angiotensinogen,AGT)基因多态性及单倍型与原发性高血压的关系。方法 在335例高血压患者与196名血压正常人中采用PCR－限制性酶切片段长度多态性法检测血管紧张素原基因的多态性，同时用最大期望值方法进行两位点连锁不平衡和三位点的单倍型分析。结果 在M235T和A－20C，M235T和A－6G，A－20C和A－6G位点观察到了连锁不平衡（P＜10^-4)。病例－对照检验显示T235等位基因频率在高血压组中高于对照组，但所有单倍型频率分布在高血压组和正常对照组间差异无显著性。结论 受检人群中AGT基因各单倍型与高血压未见关联，但AGT基因T235位点可能是一种重要的高血压风险因子。     

The -159C/T Polymorphism in the CD14 Gene and Tuberculosis Risk: A Meta-Analysis

Background: The -159C/T polymorphism in the CD14 gene has been implicated in susceptibility to tuberculosis, but the results were inconclusive. The present meta-analysis aimed to perform a comprehensive assessment of the literature on the possible association between the -159C/T polymorphism and tuberculosis risk.Methods: We searched in Pubmed and Embase for studies evaluating the association between the -159C/T gene polymorphism and tuberculosis risk. Data were extracted and statistical analysis was performed using Revman 5.1 and STATA 12.0 software.Results: A total of seven case-control studies involving 3253 subjects (1,574 tuberculosis cases and 1,679 controls) were included. Combined analysis revealed an obvious association between this polymorphism and tuberculosis risk (odds ratio=1.66 and 95% confidence interval: 1.23-2.25, P<0.05 for TT vs. TC+ CC). Sub-group analysis by ethnicity suggested that the risk of tuberculosis associated with the -159C/T polymorphism was significantly elevated among Asians (odds ratio=1.87 and 95% confidence interval: 1.58-2.21, P<0.05 for TT vs. TC+ CC).Conclusion: This meta-analysis suggests that the -159C/T polymorphism in the CD14 gene contributes to tuberculosis susceptibility. To further investigate gene-gene and gene-environment interactions between this polymorphism and tuberculosis risk, more studies are needed.     

Methylenetetrahydrofolate reductase gene and susceptibility to breast cancer: a meta-analysis

The methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been linked to the risk of developing breast cancer. A meta-analysis of 18 case-control studies investigating the association between the C677T and the A1298C polymorphisms of the MTHFR gene and breast cancer (BC) was carried out. The meta-analysis included genotype data on 5467/7336 and 3768/5276 cases/controls for C677T and A1298C, respectively. In the meta-analysis, the consistency of genetic effects across different ethnicities and the effect of menopausal status for various genetic contrasts were investigated. The overall analysis for investigating the association between the C677T allele T and the risk of developing BC showed significant heterogeneity (p = 0.08, I2 = 34%) and non-significant association [odds ratio (OR) 1.02; 95% confidence interval (0.95-1.10)]. The allele contrast was not significant in Caucasians (nine studies) and in East Asians (four studies) [OR 1.03 (0.93-1.14) and OR 0.96 (0.81-1.15), respectively] or in pre-menopausal (five studies) and post-menopausal (four studies) groups [OR 1.10 (0.94-1.29) and OR 1.06 (0.95-1.18), respectively]. The genotype contrast of the homozygotes (TT vs CC) produced significant results only for pre-menopausal cases [OR 1.46 (1.05-2.03)]. The recessive model for allele T produced significant association only in pre-menopausal cases [OR 1.49 (1.09-2.03)]. The dominant model for the effect of allele T produced no significant results, overall and in each subgroup. For the A1298C polymorphism, all genotype contrasts showed lack of association, overall and in Caucasians. In summary, the accumulated evidence supports an association in pre-menopausal women. BC is a complex disease with multifactorial etiology, and therefore, case-control studies that investigate gene-environment interaction might elucidate further the genetics of the disease.     

Detection of putative functional angiotensinogen (AGT) gene variants controlling plasma AGT levels by combined segregation-linkage analysis

Previous studies have suggested that angiotensinogen (AGT) gene variants are associated with increased plasma AGT levels, and may also contribute towards the inherited component of predisposition to essential hypertension in humans. To explore the potential functionality of several AGT polymorphisms and estimate their effects, together with other sources of familial correlations, on plasma AGT, we undertook a large study involving 545 healthy French volunteers in 130 nuclear families that include 285 offspring. Plasma AGT levels were measured in all participants, and bi-allelic AGT variants were analysed as candidate functional variants at three sites in the 5'-flanking region (C-532T, A-20C, G-6A), two sites in exon 2 (M235T, T174M) and two newly identified variant sites in the untranslated sequence of exon 5 and the 3'-flanking region (C+2054A, C+2127T) of the gene. Analysis with the class D regressive model showed significant effects influencing plasma AGT levels of all AGT polymorphisms tested, with the exception of T174M. The most significant result was found at C-532T (P=0.000001), which accounts for 4.3% of total plasma AGT variability in parents and 5.5% in offspring, with substantial residual familial correlations. Maximum likelihood estimates of haplotype frequencies and tests of linkage disequilibrium between each AGT polymorphism and a putative QTL are in agreement with a complete confounding of C-532T with the QTL, when taking into account sex and generation specific effects of the QTL. However, further combined segregation-linkage analyses showed significant evidence for additional effects of G-6A, M235T and C+2054A polymorphisms after accounting for C-532T, which supports a complex model with at least two functional variants within the AGT gene controlling AGT levels.