MTRR基因A66G多态性与子痫前期发生的相关研究

目的研究蛋氨酸合成酶还原酶(MTRR)基因A66G多态性与子痫前期发生的关系。方法采用聚合酶链反应—限制性片段长度多态性(PCR-RFLP)法对32例子痫前期,70例正常妊娠女性MTRR的A66G进行基因分析。比较上述各组基因型和等位基因频率分布有无差异。结果MTRR基因A66G突变型等位基因G频率在实验组和对照组中有显著性差异,GG基因型频率分布差异有显著性(P<0.05)。AG基因型比AA基因型发生子痫前期风险高1.98倍,GG基因型比AA基因型发生子痫前期风险高5.2倍。结论MTRR A66G基因多态性与子痫前期发生相关,AG、GG基因型增加了子痫前期的发生风险。     

MTHFR、MTRR基因多态性与反复流产的相关性分析

目的探讨叶酸代谢相关基因5,10-亚甲基四氢叶酸还原酶(MTHFR)、甲硫氨酸合成酶还原酶(MTRR)多态性与反复流产的关系,分析基因多态性对红细胞叶酸水平的影响。方法选取2016年12月至2018年6月来唐山市妇幼保健院遗传咨询门诊,要求进行常规孕前检查,汉族非妊娠健康女性424例为研究对象。依据不良孕产史分为两组,其中病例组216例和对照组218例。采集静脉血,提取DNA,荧光定量PCR法进行MTHFR、MTRR基因多态性检测。化学发光法进行红细胞叶酸定量检测。采用SPSS19.0软件进行统计学分析。比较两组MTHFR、MTRR基因多态性分布频率、不同基因类型红细胞叶酸水平。探讨基因多态性、红细胞叶酸水平与反复流产的关系。结果MTHFR A1298C和MTRR A66G两位点多态性在病例组和对照组间的分布,差异无统计学意义。MTHFR C677T位点多态性,在病例组中的分布频率明显高于对照组,差异具有统计学意义。病例组中MTHFR C667T位点TT型基因突变的患者红细胞叶酸水平远低于正常和杂合型。结论MTHFR C677T基因突变与反复流产的密切相关,MTHFR C667T位点TT型基因突变影响机体红细胞叶酸代谢水平。     

人蛋氨酸合成酶还原酶A66G基因突变频率的检测

目的 建立一种简便、准确、实用的人蛋氨酸合成酶还原酶(MSR)A66G基因突变频率的检测方法,并了解汉族人MSR基因的分布特点。方法 应用聚合酶链反应(PCR)特异性扩增蛋氨酸合成酶还原酶(MSR)A66G基因序列,扩增产物用限制性内切酶NdeI酶切,聚丙烯酰胺凝胶电泳后,观察酶切位点的限制性片段长度多态性(RFLP)图谱。结果 运用PCR-RFLP法检测了150名汉族人蛋氨酸合成酶还原酶(MSR)A66G基因点突变,其中野生型纯合子频率为25.33％,杂合子频率为52.00％,突变型纯合子频率为22.67％。突变等位基因频率为0.4867。结论 该方法简便、快速、准确,适合于一般实验室检测及大规模的人群调查,汉族人MSR基因的分布与其他地区人群的分布无明显差异。     

动脉粥样硬化性脑梗塞与低密度脂蛋白受体基因NcoI、AvaⅡ多态性的关系

目的 探讨动脉粥样硬化性脑梗死（atherosclerotic cerebral infarction,ACI)与低密度脂蛋白受体（low density lipoprotein receptor,LDL-R)基因NcoI、AvaⅡ多态性的关系。方法 用聚合酶链反应技术检测113名辽宁藉汉族健康人和77例ACI患者的LD－R基因NcoI、AvaⅡ多态性及血脂、载脂蛋白的含量。结果 LDL－R基因NcoI、AvaⅡ等位基因频率健康人N^ 为0．667、A^ 为0．230；ACI组N^ 为0．662、A^ 为0．125。A^-A^-与N^ N^ 联合存在时ACI的发病相对风险率（RR）为5．56（P＜0．001），引起血清TG、TC、LDL－C、LP（a)升高的相对风险率依次为4．29、7．67、9．33、3．09（P＜0．05）。结论 LDL－R基因A^-A^-与N^ N^ 联合存在影响血脂、脂蛋白的含量，与ACI密切相关。     

动脉粥样硬化性脑梗塞患者载脂蛋白B基因的MspI限制性…

为了解动脉粥样硬化性脑梗塞与载脂蛋白代谢异常的关系，利用Ａｐｏｂ ｃＤＮＡ探针检测了５４名ＡＣＩ患者和６２名正常对照者的载脂蛋白Ｂ基因ＭｓｐＩ限制性片段长度多态性等位基因频率。结果显示，１１６例标本共出现２．３５ｋｂ（Ｍ１）和２．６０ｋｂ（Ｍ２）两条杂交片段。     

卵磷脂胆固醇酰基转移酶基因608C/T多态性与动脉粥样硬化性脑梗塞的关联研究

目的探讨卵磷脂胆固醇酰基转移酶（lecithin-cholesterol acyltransferase，LCAT）的基因LCAT 608C／T多态性在中国汉族人群中的分布及其与动脉粥样硬化性脑梗塞（atherosclerotic cerbral infarction，ACI）的关联。方法应用聚合酶链反应、单链构象多态性技术联合限制性片段长度多态性技术检测150例ACI患者和122名年龄、性别相匹配的正常对照者的LCAT 608C／T多态性。结果LCAT 608C/T位点基因型分布在ACI和对照组均符合Hardy-Weinberg平衡定律。ACI组CT基因型频率（14．0％）、T等位基因频率（7．0％）均显著高于对照组（P〈0.05）。ACI和对照组中608CC亚组HDL-C水平均高于同组内608CT亚组（P〈0．05）。结论LCAT 608C／T多态性可能为中国人群ACI易感因素，T等位基因可能与HDL-C代谢有关。     

阿尔茨海默病与蛋氨酸合成酶基因多态性的相关性探讨

目的　探讨蛋氨酸合成酶 (MS)基因A2 75 6G突变在阿尔茨海默病 (AD)发病中的意义。方法　PCR扩增 6 6例AD患者及 14 3例对照者的MS基因突变点 ,经限制性内切酶消化后行凝胶电泳确定其基因型。结果　MS基因片段PCR扩增产物长度分别为 189bp。MSA2 75 6G突变的G等位基因PCR扩增产物经HaeⅢ消化后裂解成 15 9和 30bp两个片段 ;MAD组A2 75 6G基因型频率 (% )分别为 98 4 8、1 5 2和 0 0 0 ,对照组分别为 98 6 0、1 4 0和 0 0 0 ,MSA 2 75 6G各种基因型频率在患者组与正常对照组之间的差异无显著性 (P >0 0 5 )。结论　MS多态性与AD无明显相关。     

OLR1基因多态性与动脉粥样硬化性脑梗死的相关性研究

目的探讨OLR1基因3′-UTR-C188T及G501C位点多态性与动脉粥样硬化性脑梗死的相关性。方法用PCR-LDR方法检测219例动脉粥样硬化性脑梗死患者和386例健康对照者OLR1基因3'-UTR-C188T及G501C位点基因型。结果动脉粥样硬化性脑梗死组及对照组3′-UTR-C188T基因型和等位基因分布无统计学意义。病例组G501C位点的CC+GC基因型、GC基因型频率明显高于对照组(P=0.04,P=0.03)。病例组G501C位点的GC基因型频率,在校正传统危险因素后仍明显高于对照组,且差异有统计学意义(OR=1.535,95%CI=1.044-2.256,P=0.03)。结论 OLR1基因G501C位点多态性与动脉粥样硬化性脑梗死的发病具有相关性,可能是动脉粥样硬化性脑梗死发病的危险因素。     

纤维蛋白原Bβ多态基因FGB-455G/A多态性与动脉粥样硬化性脑梗塞的关系

目的　探讨纤维蛋白原 (fibrinogen ,FGB )Bβ多态基因FGB 45 5G/A多态性在中国汉族人群中的分布及其与动脉粥样硬化性脑梗塞 (atheroscleroticcerebralinfarction ,ACI)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检测了 13 2例ACI患者和 14 8名年龄、性别相匹配的正常对照者的Bβ基因FGB -4 5 5G/A多态性 ,比浊法测定血浆纤维蛋白原水平。 结果　血浆纤维蛋白原水平在ACI组显著高于正常对照组 (P <0 .0 0 1)。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 ,且更易受吸烟等环境因素影响。Bβ基因FGB -4 5 5G/A多态性分布在患病组和对照组均符合Hardy Weinberg平衡定律。A等位基因频率在ACI组 ( 0 .2 5 8)显著高于正常对照组 ( 0 .15 2 ) (P <0 0 5 )。Logistic回归分析发现 ,存在此突变位点者发生ACI的危险提高了 65 .3 %。结论　Bβ基因FGB -4 5 5G/A多态性中的A等位基因可能是中国人缺血性脑血管疾病的遗传易感标志之一。     

载脂蛋白A5基因多态性与动脉粥样硬化性脑梗死的关联研究

目的探讨载脂蛋白A5基因(apolipoprotein A5 gene,APOA5)多态性与动脉粥样硬化性脑梗死(atherosclerotic cerebral infarction,ACI)的关联性及与血脂的关系。方法用聚合酶链反应-限制性片段长度多态性分析170例ACI患者和171名健康对照-12238T>C位点多态性。结果T/C多态位点等位基因T、C频率在ACI组和正常对照组分别为0.588、0.412和0.424、0.576,等位基因T、C频率在两组间差异有统计学意义(P<0.05),且TT基因型的ACI患者其血浆甘油三酯(triglyceride,TG)水平明显高于CC型患者(P<0.05)。结论-12238T>C位点多态性可能与ACI存在关联,ACI组TT基因型可能与血浆TG水平密切相关。     

蛋氨酸合成酶基因多态性与颅内动脉瘤的关系

目的 探讨同型半胱氨酸和蛋氨酸合成酶(MS)A2756G基因多态性与颅内动脉瘤的关系.方法 运用多聚酶链反应技术和化学发光法检测76例颅内动脉瘤及77例正常人MS A2756G基因多态性.结果 颅内动脉瘤组的MS D919G DG基因型频率较正常对照高(P ＜ 0.01),患颅内动脉瘤的风险是对照组的6.35倍.两组等...     

Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) in ethnic populations in Texas; a report of a novel MTHFR polymorphic site,G1793A

The importance of hyperhomocysteinemia, birth defects, and vascular diseases has been the subject of intense investigations. The polymorphic MTHFR mutations (C677T and A1298C) cause mild hyperhomocysteinemia, especially in homozygotes for C677T, but also in compound heterozygotes for C677T/A1298C. The subject of this report is the frequency of the polymorphic mutations in the MTHFR gene C677T, C1298A, and newly discovered mutation G1793A, as well as the association with MTRR polymorphic site A66G in different ethnic groups. Four ethnic groups were studied: African‐Americans, Caucasians, Hispanics, and Ashkenazi Jews. There are statistically significant differences in the frequency of these alleles in the different populations studied, which impacts compound heterozygosity for such alleles in these populations. DNA samples obtained from the blood of healthy individuals of African‐Americans, Hispanics, and Caucasians from south Texas were analyzed and compared to those obtained from Ashkenazi Jewish individuals. The polymorphic site, the G1793A allele, is least frequent among Ashkenazi individuals, 1.3%, compared to 6.9% among Caucasians (P = 0.001), 5.8% among Hispanics (P = 0.012), and 3.1% among African‐Americans. The MTRR polymorphic site shows the lowest allele frequency among Hispanics, 28.6%, compared to 34% among African‐Americans, 43.1% among Ashkenazi Jews (P = 0.002), and 54.4% among Caucasians (P < 0.0001). Statistically significant differences in allele frequencies of C677T and C1298A polymorphisms were also observed in these populations. Compound heterozygosity for multiple polymorphic alleles may play a role in birth defects and vascular diseases. © 2001 Wiley‐Liss, Inc.     

Influence of combined methionine synthase (MTR 2756A > G) and methylenetetrahydrofolate reductase (MTHFR 677C > T) polymorphisms to plasma homocysteine levels in Korean patients with ischemic stroke

PURPOSE: Methionine synthase (MTR) and 5,10-methylenetetrahydrofolate reductase (MTHFR) are the main regulatory enzymes for homocysteine metabolism. The present case- control study was conducted to determine whether there is an association between the MTR 2756A > G or MTHFR 677C > T polymorphism and plasma homocysteine concentration in Korean subjects with ischemic stroke. MATERIALS AND METHODS: DNA samples of 237 patients who had an ischemic stroke and 223 age and sex-matched controls were studied. MTR 2756A > G and MTHFR 677C > T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Frequencies of mutant alleles for MTR and MTHFR polymorphisms were not significantly different between the controls and cases. The patient group, however, had significantly higher homocysteine concentrations of the MTR 2756AA and MTHFR 677TT genotypes than the control group (p=0.04 for MTR, p=0.01 for MTHFR). The combined MTR 2756AA and MTHFR 677TT genotype (p= 0.04) and the homocysteine concentrations of the patient group were also higher than those of the controls. In addition, the genotype distribution was significant in the MTHFR 677TT genotype (p=0.008) and combined MTR 2756AA and MTHFR 677TT genotype (p=0.03), which divided the groups into the top 20% and bottom 20% based on their homocysteine levels. CONCLUSION: The results of the present study demonstrate that the MTR 2756A > G and MTHFR 677C > T polymorphisms interact with elevated total homocysteine (tHcy) levels, leading to an increased risk of ischemic stroke.     

Methionine Synthase Reductase (MTRR) A66G polymorphism is not related to plasma homocysteine concentration and the risk for vascular disease

Epidemiological evidence has revealed that hyperhomocysteinemia increases the risk for vascular disease. Methionine Synthase Reductase (MTRR) is one of several key enzymes in the homocysteine metabolic pathway and its mutant forms have been implicated in abnormal homocysteine accumulation. In this study, we determined total plasma homocysteine levels and MTRR A66G polymorphism in 114 patients with vascular disease: 58 patients with deep-vein thrombosis, 56 patients with arterial thrombosis, and 95 healthy subjects from the Sicilian population. Our data confirmed that, as already reported, moderately elevated t-Hcy levels are correlated with an increased risk of vascular disease. In our study, the levels of t-Hcy found in both deep-vein thrombosis (13.7 ± 3.2 μmol/L) and arterial thrombosis (14.3 ± 4.3 μmol/L) patient groups were higher than levels detected in normal subjects (8.7 ± 2.7 μmol/L).We concluded that the MTRR A66G polymorphism was not associated with the t-Hcy plasma concentration because the same genotype frequency distribution was detected in both patients and healthy individuals.     

MTHFR基因C677T多态性与Down综合征发生的相关研究

目的研究亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性与Down综合征关系。方法采用聚合酶链反应—限制性片段长度多态性(PCR-RFLP)法对32例DS患儿母亲,70例未生育DS患儿女性MTHFR的C677T进行基因分析。比较上述各组基因型和等位基因频率分布有无差异。结果MTHFR基因C677T突变型等位基因(T)频率在实验组和对照组中有显著性差异,CC、TT基因型频率分布差异有显著性(P<0.05)。CT基因型比CC基因型生育DS患儿风险高2.84倍,TT基因型比CC基因型生育DS患儿风险高9.26倍。结论MTHFRC677T基因多态性与Down综合征发生相关,TT基因型增加了Down综合征的发生风险,CC基因型是降低Down综合征发生的保护性因素。     

妊娠高血压综合征与MTHFR A1298C基因及血浆同型半胱氨酸水平的关系

目的探讨妊娠高血压综合征与N5,N10鄄亚甲基四氢叶酸还原酶(MTHFRA1298C)基因及血浆同型半胱氨酸(Hcy)水平的关系。方法运用多聚酶链反应鄄限制性内切酶片段长度多态性技术(PCR鄄RFLP)检测54例妊高征患者,100例正常妊娠妇女(MTHFRA1298C基因多态性,采用荧光偏振免疫法(FPIA)测定血浆总Hcy水平。结果MTHFRA1298C三种基因型频率与对照组相比差异无显著性,与患者不同临床特征无明显关联。妊高征组总Hcy水平明显高于正常妊娠组(P<0.05)。结论MTHFRA1298C基因突变与妊高征发生无关;高同型半胱氨酸血症是妊高征发病的一个新的危险因素。     

MTHFR基因多态性与老年冠心病及同型半胱氨酸的相关性研究

目的探讨N5,N10亚甲基四氢叶酸还原酶（MTHFR）基因多态性及血浆同型半胱氨酸（Hcy）与老年冠心病的相关性。方法应用高效液相色谱法和多聚酶链反应限制性内切酶片段长度多态性技术检测并比较了120例老年冠心病患者（CHD组）和58例健康老年人（对照组）的血浆Hcy浓度及MTHFR基因型。结果两组MTHFR 677位点基因型分布和各等位基因频率比较均有统计学差异（P均〈0.05）;CHD组T等位基因频率及血浆Hcy浓度高于对照组（P均〈0.05）。结论 MTHFR基因突变可导致血浆Hcy浓度升高,高Hcy浓度及MTHFR基因T型均为老年CHD的高危因素。