叶酸代谢过程相关的四个单核苷酸多态性位点与先天性心脏病发病风险的病例-对照研究

目的研究5,10-亚甲基四氢叶酸还原酶(MTHFR)C677T和A1298C位点,蛋氨酸合成酶(MS)A2756G位点,以及蛋氨酸合成酶还原酶(MTRR)A66G位点的单核苷酸多态性(SNPs)和先天性心脏病(CHD)的关联。方法采用病例-对照研究,限制相应条件于2016年1月—2017年4月在河北省儿童医院心脏外科收集了200名CHD患儿作为病例组,200名正常体检儿童作为对照组。通过聚合酶链式反应(PCR)后Sanger测序的分析方法检测两组儿童的MTHFR C677T和A1298C位点、MS A2756G位点以及MTRR A66G位点的基因型及其分布,分析上述4个SNP位点与整体CHD和单一以及多发畸形型CHD发病风险之间的关系。结果 MTHFR C677T位点等位基因T携带者相对于等位基因C携带者发生CHD的OR=2.47(95%CI 1.86~3.29,P0.001)。与纯合子CC型比较,杂合子CT个体患CHD的OR=2.32(95%CI 1.35~3.98,P0.05),而突变型纯合子TT个体患CHD的风险是CC个体的5.37倍(95%CI 3.01~9.60,P0.001);MTHFR A1298C位点等位基因C携带者相比于等位基因A携带者发生CHD的OR=0.53(95%CI 0.36~0.77,P0.05)。杂合子AC个体患病风险低于野生型纯合子AA个体(OR=0.41,95%CI 0.26~0.64,P0.001);在分类后的单一及多发畸形型CHD中,以上两个位点的等位基因频率及基因型频率依然具有统计学意义(P0.05)。以上两位点的组合基因型分析显示:相比于携带双野生型CC/AA的个体,携带CT/AA个体的患病风险增加到了4.65倍(95%CI 2.16~10.02),TT/AA型个体增加到了7.05倍(95%CI 3.37~14.79)。统计结果表明MS A2756G和MTRR A66G位点对整体CHD以及对分类后的单一及多发畸形型CHD的发生均无影响(P0.05)。结论 MTHFR C677T位点的突变型等位基因T可能为CHD的危险因素,A1298C位点的突变型等位基因C可能是CHD的保护因素,这两个位点对CHD的发生可能存在联合作用。     

eNOS基因T-786C变异与早发冠心病关系

目的探讨内皮型-氧化氮合酶（eNOS）基因T-786C变异与早发冠心病的关系。方法以188例早发冠心病为病例组,315例迟发冠心病为对照组,运用PCR-（限制性片断长度多态性）（RFLP）方法检测eNOS基因T-786C变异;应用单因素及多元逐步Logistic回归分析eNOS基因T-786C变异与早发冠心病的关系。结果T-786C基因型频率早发冠心病组与迟发冠心病组比较,差异无统计学意义（P=0.105）,但TC＋CC基因型频率早发冠心病组显著高于迟发冠心病组（P=0.039）。C等位基因频率早发冠心病组（14.63%）也显著高于迟发冠心病组（10.32%）（P=0.041,OR=1.489,95%CI=1.014～2.187）。在0.05显著水平上,用多元逐步Logistic回归分析调整性别、吸烟、饮酒、超重后,T-786C变异仍对早发冠心病具有显著影响（P=0.013,OR=1.791,95%CI=1.131～2.897）。结论eNOS基因T-786C变异可能是早发冠心病的重要危险因素之一。     

eNOS基因G894T位点多态性与急性高原病关联的研究

目的观察内皮型一氧化氮合酶(e NOS)基因第7外显子G894T位点基因多态性与急性高原病(AMS)的关联。方法选取入高原(海拔3700 m)新兵200人为研究对象,监测入高原后AMS发病情况,得出AMS发病率及症状评分,同时检测e NOS基因G894T多态性,确定该位点多态性是否与AMS发病率及症状评分存在关联。结果该组人群AMS发病率33.53%,无高原肺水肿、脑水肿病例,基因多态性分析共检测出三种基因型:GG型、GT型、TT型,其中GG型89人(71.77%),GT型31人(25.00%),TT型4人(3.23%),GG型人群AMS发病率及症状评分显著低于GT型人群(24.72%vs 58.06%,2.51±2.10 vs 4.71±2.49)。结论 e NOS基因G894T位点多态性与AMS存在关联。     

MTHFR的基因多态性与原因不明复发性流产的相关性分析

目的：探讨原因不明复发性流产（URSA）与5,10-亚甲基四氢叶酸还原酶（MTHFR）基因多态性的关系。方法：采用荧光定量聚合酶链反应（PCR）技术,对83例URSA患者（URSA组）和90例健康育龄期妇女（对照组）行MTHFR基因C667T、A1298C位点单核苷酸多态性分析,比较2组患者基因型、等位基因频率分布情况,并评估不同基因型致URSA发生的风险。结果：2组患者MTHFR基因型分布符合Hardy-Weinberg平衡。2组患者MTHFR C677T基因型、等位基因频率分布比较差异有统计学意义（均P＜0.05）;MTHFR A1298C基因型、等位基因频率分布比较差异无统计学意义（均P＞0.05）。URSA组TT纯合子出现频率高于对照组（30.1% vs. 13.3%, χ2=7.237,P=0.007）。TT纯合子基因型发生URSA的风险是CC纯合子基因型的3.289倍（OR=3.289,95%CI：1.342～8.063）。结论：MTHFR C677T位点基因多态性与URSA的发生有关,TT纯合子基因型可增加患病风险。     

汉族及哈萨克族IL-6基因-174G/C多态性及CRP基因+1059G/C多态性与代谢综合征的相关性研究

[目的]探讨新疆哈萨克族及汉族IL-6基因-174G/C及哈萨克族CRP基因+1059G/C多态性与代谢综合征(MS)的相关性。[方法]应用PCR-RFLP方法分别对新疆哈萨克族及汉族200例MS组及201例对照组IL-6基因-174G/C位点及哈萨克族200例MS组及201例对照组CRP基因+1059G/C位点进行检测。[结果]①IL-6-174G/C位点:哈萨克族两组中GG型频率分别为94.00%和98.50%,GC型分别为6.00%和1.50%,在MS组中CC型有1例被检出,两组基因型对比差异有统计学意义(χ2=5.66,P﹤0.05),G和C等位基因频率分别为97.00%和3.00%,对照组分别为99.30%和0.70%;两组等位基因频率差异有统计学意义(χ2=5.55,P﹤0.05),以G等位基因为参照,C等位基因的OR值为4.12(OR95%CI:1.38～12.29);汉族两组中GG型频率分别为93.43%和97.51%,GC型分别为6.57%和2.49%,CC型在两组中未检出,两组基因型差异有统计学意义(χ2=4.52,P﹤0.05),MS组中G和C等位基因频率分别为96.71%和3.29%,对照组中分别为98.76%和1.24%,G和C等位基因频率在两组间差异有统计学意义(χ2=4.42,P﹤0.05),以G等位基因为参照,C等位基因的OR为2.88(OR95%CI:1.08～7.70);两民族MS组及对照组IL-6-174位点基因型及等位基因频率的差异均无统计学意义(P﹥0.05);②CRP+1059G/C位点:MS组与对照组GG基因型频率分别为93.00%和99.00%,GC基因型频率分别为7.00%和1.00%,CC基因型未检出,G和C等位基因频率在MS组分别为96.50%和3.50%,两组基因型差异有统计学意义(χ2=9.43,P﹤0.01),等位基因频率差异有统计学意义(χ2=9.24,P﹤0.01),以G等位基因为参照,C等位基因的OR值为7.25(2.04～25.76)。[结论]哈萨克族和汉族IL-6-174G/C及哈萨克族CRP+1059G/C基因多态性与MS有一定关联。     

BRCA1基因单核苷酸多态性与广东汉族女性散发性乳腺癌易感相关性研究

目的探讨BRCA1基因启动子区rs799906位点和编码区rs799917位点单核苷酸多态性(single nucleotide polymorphism,SNP)与广东汉族女性散发性乳腺癌易感性的关系。方法利用Sequenom Mass Array iPLEX GOLD系统对107例散发性乳腺癌患者及93例健康对照者的BRCA1基因两个SNP位点(rs799906,rs799917)进行检测,并对检测结果进行χ2检验和非条件Logistic回归分析。结果 rs799906位点TT、TC和CC三种基因型在病例组和对照组的分布频率有差异(χ2=8.407,P=0.018)。相对TT基因型而言,TC杂合型能增加乳腺癌发生的危险性(OR=2.566;95%CI:1.101～5.983;P<0.05),但等位基因T和C的频率分布无显著差异(χ2=2.169,P=0.141)。rs799917位点CC、CT和TT三种基因型的频率和等位基因C和T的频率在病例组和对照组的分布均无显著性差异(χ2=3.994,P=0.136;χ2=0.903,P=0.342)。结论 BRCA1多态性位点rs799906TC杂合型与散发性乳腺癌发病风险有相关性;而rs799917位点多态性与散发性乳腺癌发病风险无相关性。     

硒蛋白S基因多态性与布鲁氏菌病遗传易感性的关联性

目的 检测内蒙古包头地区布鲁氏菌病患者硒蛋白S（selenoprotein S,SelS）基因rs28665122、rs34713741位点基因型和等位基因分布频率,探讨SelS基因多态性与本地区布鲁氏菌病患者遗传易感性的关联性。方法 采用一种快速点突变检测技术-等位基因特异性PCR（allele - specific PCR,AS - PCR）技术检测32例慢性期布鲁氏菌病患者和30例健康对照者SelS基因（rs28665122、rs34713741）基因型和等位基因分布频率。结果 布鲁氏菌病患者组与对照组SelS基因rs28665122位点GG、GA、AA基因型及G、A等位基因频率比较无统计学差异（χ2分别为0.203,0.852,均P＞0.05 ）;rs34713741位点CT、CC、TT基因型和C、T等位基因分布频率比较存在统计学差异（χ2分别为9.209,6.580,均P＜0.05）,与C等位基因相比,携带T等位基因者感染布鲁氏菌风险增高3.194倍（OR = 3.194,95%CI:1.489～6.847）,与CC基因型相比,CT和TT基因型者感染布鲁氏菌风险均增高（OR = 3.273,95%CI:0.876～12.223;OR = 4.364,95%CI:1.217～15.641）。结论 本地区布鲁氏菌病与SelS基因rs34713741位点基因多态性有关联,T等位基因可能是其风险易感基因。     

冠心病与NAD(P)H氧化酶p22phox基因C242T多态性

目的探讨烟酰胺腺嘌呤二核苷酸磷酸盐氧化酶[NAD(P)H氧化酶]p22phox基因C242T多态性与冠心病的关系。方法采用病例对照研究方法,收集早发冠心病患者309例,迟发冠心病患者437例,对照470例,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)基因分型技术对p22phox基因C242T位点的多态性进行检测;采用单因素和多因素logistic回归计算p22phox基因C242T多态性与冠心病风险的OR值及95%CI。结果与对照组比较,早发冠心病组携带TC+TT基因型的个体比携带CC基因型更容易患冠心病,OR=1.58,95%CI=1.07～2.34;迟发冠心病组OR=1.48,95%CI=1.03～2.13;多因素调整后,与对照组比较,早发冠心病组OR=1.74,95%CI=1.16～2.62;2个病例组比较,携带TC+TT基因型与携带CC基因型的患病风险差异均无统计学意义。结论p22phox基因C242T多态性的T等位基因可能是冠心病的危险因素。     

TCF7L2和KCNQ1基因多态性与2型糖尿病易感性的Meta分析

目的对TCF7L2,KCNQ1基因多态性与2型糖尿病(T2DM)相关性的研究进行Meta分析。方法通过检索PubMed和CNKI数据库中有关TCF7L2,KCNQ1基因多态性与T2DM易感性关联研究的文献,用漏斗图检验入选文献的偏倚,根据异质性检验结果采用固定效应模型或随机效应模型进行Meta分析,此过程均在软件包Launch Stata11.0上完成。结果该研究共纳入20篇文献(:1)KCNQ1基因rs2237892位点与T2DM发病风险相关性的研究共纳入7篇,得到7764例T2DM患者和8937例对照,Meta分析结果显示,rs2237892位点C等位基因能够增加T2DM的发病风险(OR=1.300,95%CI:1.234～1.366);CC/TC基因型是T2DM的危险基因型(OR=1.453,95%CI:1.279～1.651)。(2)TCF7L2基因rs7903146位点与T2DM发病风险相关性研究12篇,共得到11443例2型糖尿病患者和11003例对照,Meta分析结果显示,rs7903146位点T等位基因能够增加T2DM的发病风险(OR=1.379,95%CI:1.261～1.508),TT/TC基因型是T2DM的危险基因型(OR=1.469,95%CI:1.333～1.620)。(3)TCF7L2基因rs12255372位点与T2DM发病风险相关性的研究12篇,共得到12173例T2DM患者和10869例对照;Meta分析结果显示,rs12255372位点T等位基因能够增加T2DM的发病风险(OR=1.381,95%CI:1.275～1.495),TT/TG基因型是T2DM的危险基因型(OR=1.463,95%CI:1.337～1.602)。结论 TCF7L2基因rs7903146位点TT/TC基因型和rs12255372位点TT/TG基因型,以及KCNQ1基因rs2237892位点CC/TC基因型均能够增加T2DM的发病风险。     

内皮型一氧化氮合酶基因多态性与2型糖尿病并发冠心病的相关性研究

目的探讨汉族人内皮固有型一氧化氮合酶(ecNOS)基因外显子7单核苷酸多态性(G894T)和内含子4可变数目串联重复序列插入/缺失多态性(4b/a)与2型糖尿病(T2DM)并发冠心病的关联性。方法提取80例T2DM患者、92例T2DM并发冠心病患者及119例健康人的基因组DNA,用聚合酶链反应—限制片段长度多态性法测定G894T多态性,用聚合酶链反应-可变数目串联重复序列法测定4b/a多态性。结果3组间G894T多态性基因型(χ2=11.112,P=0.004)和等位基因(χ2=12.262,P=0.002)频率分布存在统计学差异;3组间4b/a多态性基因分布无差别;携带T等位基因的T2DM患者较之GG基因型者发生冠心病的危险性升高(OR=3.293,P=0.005)。结论ecNOS基因894位点T等位基因是T2DM并发冠心病的独立危险因素。4b/a多态性与T2DM或T2DM并发冠心病无关。     

Blood pressure and the T174M and M235T polymorphisms of the angiotensinogen gene.

PURPOSE: The angiotensinogen gene (AGT), which encodes the precursor of the vasoactive hormone angiotensin II, has been reported to be associated with hypertension in Caucasian and Japanese populations. We examined the relationship between two common molecular variants of AGT, T174M and M235T and blood pressure in two cohorts from the Anqing region of China. Cohort I (N = 794) consisted of families ascertained by either hypertensive or hypotensive siblings; and Cohort II (N = 761) represented a collection of randomly selected families. METHODS: Blood pressure was measured according to standard protocols, and information on age, sex, body mass index, alcohol consumption, and cigarette smoking was collected by trained interviewers using standardized questionnaires. The association of AGT genotypes and blood pressure was examined in multivariate linear regression models, with adjustment for potential intrafamilial correlations. The respective T and M allele frequencies for T174M were 0.93 and 0.07, and 0.80 and 0.20 for M235T among the parents for randomly selected families. All the analyses were conducted after exclusion of individuals currently under antihypertensive medication. RESULTS: In the pooled analysis of the two cohorts, neither the T174M nor the M235T polymorphism was significantly associated with variations of blood pressure assuming a recessive (T174M: p = 0.73 and 0.61; M235T: p = 0.99 and 0.24; for SBP and DBP), dominant (T174M: p = 0.54 and 0.72; M235T: p = 0.79 and 0.12; for SBP and DBP), or additive (T174M: p = 0.52 and 0.67, M235T: p = 0.91 and 0.11; for SBP and DBP) model. Likewise, no statistically significant association was detected when the two cohorts were analyzed separately. The logistic regression analysis of hypertension also failed to reveal any association with these markers. CONCLUSIONS: In summary, our analyses suggest that the molecular variants of AGT may not be associated with variations of blood pressure in this rural Chinese population.     

引文网络加速转化医学T1-T2-T3阶段的转化进程

Dougherty和Conway的转化医学“3T”模式体现了T1（基础研究到临床有效性研究）、T2（临床有效性研究到临床疗效研究）、T3（临床疗效研究到与经济有关的研究和改进医疗服务质量）阶段的相互转化过程,可作为测量转化研究的基础框架。文献之间的引用与被引用关系形成的“引文网络（citation network）” 揭示出具体领域的转化地带、转化路径和转化时滞,可使科研人员把握该领域转化研究的关键内容与路线图,促进研究从上游吸收和向下游转化,最终加速转化医学进程。利用文献的引文网络可对不同研究阶段之间的转化关系进行测量。本文基于文献“引文网络”分析方法,介绍“3T”模式下的转化研究测量模型。     

A randomized trial of the Gyne T 380 and Gyne T 380 Slimline Intrauterine Copper devices

To facilitate manufacture and insertion of the Gyne T 380 IUD, design changes were instituted. Copper collars were seated flush at the ends of the horizontal crossbar of the device. A randomized study of the Gyne T 380 Slimline, the new design, was undertaken in comparison with the standard Gyne T 380. A total of 996 women were enrolled, with 698 Slimline insertions and 298 of the standard Gyne T. No statistically significant difference in ease of insertion or in performance was detected between the models. At one year, the pregnancy rate of each model was below 0.5 per 100 and the continuation rate was 79-80 per 100. Pelvic inflammatory disease or endometritis was found in one percent of subjects in the first year. This is the seventh multicenter randomized study of a collared T IUD with 380 mm2 of copper surface. In all seven, the one-year gross pregnancy rate has been 1.2 per 100 or lower.     

Return of fertility after the removal of Nova T or Copper T 200

The return of fertility after removal of Nova T or Copper T 200 IUDs was studied in 150 women who had a removal for planning pregnancy in a study performed for the comparison of the clinical performance of these IUDs in Denmark, Finland and Sweden. There was no significant difference in the return of fertility of women having used either device. The cumulative probability of pregnancy per 100 women after the removal of the IUD, as a net rate, was 77.3 at one year, 88.9 at two years and 92.4 at three years.The return of fertility was analyzed separately for those women who had used their IUD for less than two years and for two or more years. The duration of the use had no significant effect on the return of fertility. The outcome of pregnancy, the birth weight, the condition at delivery and the sex ratio of the newborns were normal in the participating countries.     

Difference between T1 and T2 weighted MR images in avascular necrosis of the femoral head

T1 and T2 weighted MR images were compared in 32 hips with avascular necrosis, and the difference between them was discussed. In 27 of 32 hips, abnormal low intensity area in the affected femoral head is smaller in T2 weighted images than in T1 weighted images. The area of low intensity on T1 weighted image and high on T2 weighted image might be granuloma in reactive tissue and surrounding hyperemia. The difference between T1 and T2 weighted images must be taken into consideration especially in determination of the border of affected bone.     

Determining the thyroid hormones T3 and T4 in the urine: an unreliable test for hypothyroidism

A 24-year-old woman complained of tiredness, sensitivity to cold, and feelings of depression. A diagnosis of hypothyroidism based on decreased 24 h urinary T3 and T4 excretion was made, and she was treated with levothyroxin. No blood tests were done. She was referred with the question if she had other endocrine disorders. Her periods were regular, and on physical examination no abnormalities except slight acne were found. Similarly, hypothyroidism was diagnosed by decreased thyroid hormone excretion in 24 h urine, again without blood tests, in a 68-year-old woman whose mother had a goitre, and who had already been prescribed liothyronine. She had no complaints, and physical examination was unremarkable. The thyroid gland was not palpable. Thyroid peroxidase antibodies were absent in both patients. After discontinuation of medication with thyroid hormones they both remained euthyroid. It is concluded that thyroid disease did not exist in those 2 patients. Measurement of 24 h urinary T3 and T4 excretion is not an accurate diagnostic test for hypothyroidism.     

硫酸镍对大鼠血清T_3、T_4、TSH含量的影响

４０只Ｗｉｓｔａｒ雄性大鼠分四组，１，２，３组分别皮下注入０．００５，０．０１，０．０２ｍｏｌ／ＬＮｉＳＯ４１ｍｌ／（ｋｇ·ｄ），第四组皮下注射生理盐水作为对照。４０天后０．０１ｍｏｌ／Ｌ及０．０２ｍｏｌ／ＬＮｉＳＯ４组血清Ｔ３、Ｔ４均低于对照组（Ｐ＜０．０５或Ｐ＜０．０１），０．００５ｍｏｌ／ＬＮｉＳＯ４组Ｔ４亦低于对照组（Ｐ＜０．０５），而各剂量ＮｉＳＯ４组间血清Ｔ３、Ｔ４均无差异，即无剂量－效应关系。各剂量组血清ＴＳＨ与对照组无明显差异（Ｐ＞０．０５）。此外，甲状腺上皮细胞增生，粗面内质网高度扩张，胞核变形。提示Ｎｉ２＋对甲状腺有一定损害。