钙蛋白酶抑制蛋白基因座多态性与散发性帕金森病晚期发作的关联性分析

目的 探讨中国汉族人群中钙蛋白酶抑制蛋白(CAST)基因座单核苷酸多态性与散发性帕金森病(PD)的晚期发作之间的关联性.方法 取370名PD晚发患者和390名无神经系统疾病健康对照,取外周血提取DNA,使用基质辅助激光解析串联飞行时间质谱仪(MALDI-TOF-MS)对CAST基因的24个标签单核苷酸多态性(SNPs)进行基因分型,用x2-检验、logistic回归模型以及以贝叶斯算法(Bayesian algorithm)为基础的PHASE软件进行统计学分析.结果 在共显性基因模式中,未发现任何SNP与PD显著相关(P＞0.05);用年龄和性别校准后,进一步进行Logistic回归分析显示,在显性基因模式和隐性基因模式中均未发现任何CAST的基因多态性与PD有相关性(P＞0.05).连锁不平衡分析发现4个强连锁不平衡区域,未发现任何单倍型与PD发病密切相关(P＞0.05).结论 在中国汉族人群中,CAST与散发性PD的晚期发作无显著关联性.     

我国汉族人群SARS患者MxA基因-88位点的多态性研究

[目的]研究我国汉族SARS患者MxA基因-88位点的基因多态性.[方法]应用PCR-RFLP的研究方法进行MxA基因-88位点的基因多态性（SNP）分型.[结果]我国汉族SARS患者MxA基因-88位点的GG、GT、TT基因型构成分别为51.7%、36.7%和11.7%,与健康人群该位点的基因型构成无差别（x^2=0.855,P=0.642）.同时,该位点的G和T等位基因构成分别为70%和30%,与健康人群该位点的等位基因构成相近（x^2=0.033,P=0.857）.[结论]我国汉族SARS患者MxA基因-88位点的基因多态性与健康人群无显著性差异.     

ACE基因多态性与汉族扩张型心肌病的相关性

目的探讨血管紧张素转化酶（ACE）基因多态性与汉族扩张型心肌病的相关性。方法收集2005年以来101例汉族扩张型心肌病病人及体检科105例汉族健康体检者血液DNA,利用PCR扩增技术检测ACE基因缺失/插入多态性,记录基因分型结果并进行统计学分析。结果 ACE三种基因型II、ID、DD在扩张型心肌病患者中的分布频率分别为20%、48%、32%,在汉族正常对照中的分布频率分别为29%、50%、21%。等位基因I与D在扩张型心肌病患者中的分布频率为44.5%、55.5%,在对照组中的分布频率为53.8%、46.2%。统计学分析结果显示基因型分布频率及等位基因频率分布在两组间均具有显著差异（P〈0.01）。结论汉族人群中ACE基因多态性与汉族扩张型心肌病具有显著关联性,等位基因D可能是扩张型心肌病的易感基因。     

上海地区汉族人群IL-17B基因单核苷酸多态性的研究

目的:研究上海地区汉族人群IL-17B基因单核苷酸多态性及其分布特征,并与国外数据库进行比较。方法:随机选取190例上海地区汉族个体,对IL-17B基因启动子、外显子及临近的内含子区的PCR产物直接测序,检测基因内SNPs。所得结果与美国国立生物技术信息中心(NCBI)的SNP数据库(dbSNP)进行比较。结果:在所有研究对象中共发现6个SNPs,主要位于非编码区;6个均为替换型SNPs,其中1个为三态替换型SNP。有5个SNP在dbSNP数据库中已报导,但有11个数据库已报导的SNPs,在本次研究中未能证实。结论:中国汉族人群IL-17B基因多态性的分布与dbSNP数据库中的资料存在差异,为在汉族人群中研究IL-17B基因相关疾病提供可靠数据。     

二维应变超声对原发性扩张型心肌病及缺血性心肌病左房心肌功能评价的研究

目的应用二维应变超声测量法（2DSE）评估原发性扩张型心肌病患者及缺血性心肌病患者收缩功能的差异。方法对30例扩张型心肌病患者（50±14．6）岁及44例缺血性心肌病患者（52±16．9）岁的左房间隔部、游离壁及顶部的纵向应变进行标准多普勒超声及2DSE测量分析。结果两组患者左室容积,射血分数,二尖瓣返流面积及二尖瓣返流量差异没有统计学意义。但是,扩张型心肌病患者左房主动排空量及排空分数较缺血性心肌病患者明显减少。扩张型心肌病左房各测量部位的收缩期纵向应变峰值也低于缺血性心肌病患者。结论二维应变超声测量对于扩张型心肌病患者左房功能异常有较好的评价作用。原发性扩张型心肌病患者与缺血性心肌病相比,左房收缩期功能降低。     

我国汉族人群MxA基因-88位点的基因多态性研究

【目的】研究我国汉族人群MxA基因-88位点的基因多态性。【方法】采用聚合酶链反应-限制性片段长度多态性技术(PCR-RFLP)方法进行MxA基因-88位点的基因多态性(SNP)分型。【结果】我国汉族人群MxA基因-88位点的GG、GT、TT基因型构成分别为47.3%、43.5%和9.2%,与越南和日本的基因型构成无差别(χ2=1.56,P=0.816)。同时,该位点的G和T等位基因构成分别为69%和31%,与越南和日本的人群该位点的等位基因构成相近(χ2=0.49,P=0.783)。【结论】我国汉族人群MxA基因-88位点的基因多态性与其他民族可能相同。     

湖北地区一扩张型心肌病家系致病基因筛查

目的 对湖北地区一个扩张型心肌病家系成员进行致病候选基因筛查,寻求家族性扩张型心肌病致病基因,探讨基因型和表型关系.方法 先证者及其家族成员来自湖北省大冶市,先证者于2017年4月在武汉大学人民医院确诊为扩张型心肌病,已有家族成员死亡.详细询问先证者及其家属成员病史、家族史,并进行体格检查、血液指标、心脏超声和心电图检查.对患者的病史、家族史及检查结果分析.与先证者及其家属签订知情同意书,由武汉大学人民医院临床分子诊断中心对先证者候选致病基因全外显子高通量测序,获得可疑突变后,利用Sanger测序验证家系成员是否存在可疑突变.结果 家系先证者(Ⅲ3)和妹妹(Ⅲ2)携带肌联蛋白(TTN)c.100126A>G(P.Thr33376Ala)错义突变.先证者目前心功能下降并伴有恶性心律失常,而其妹妹无明显临床症状,心脏超声检查无异常.结论 本研究发现湖北地区一家族性扩张型心肌病家系存在TTN基因c.100126A>G(p.Thr33376Ala)错义突变,TTN与扩张型心肌病密切相关,是家族性扩张型心肌病重要致病基因.     

汉族群体血管紧张素原基因T174M多态性与心肌梗死相关

目的: 探讨血管紧张素原(angiotensinogen,AGT)基因T174M变异与中国人汉族群体心肌梗死(MI)的关系. 方法: 采用聚合酶链反应(PCR)、限制性片段长度多态性(restriction fragment length polymorphism,RFLP)分析,对105例MI患者和201例无冠心病证据的对照组(汉族群体)进行AGT基因T174M等位基因检测. 结果: MI患者AGT基因174MM型(7.6%)和M174等位基因(16.7%)的频率显著高于健康对照组(分别为1.49%和9.45%,χ2=7.57,P＜0.025,χ2=5.79,P＜0.05),经校正冠心病的主要危险因素后,AGT基因174MM仍可显著增加心肌梗死发生的危险性(比数比3.66,P=0.018).结论: AGT基因T174M可能是汉族群体MI发病的重要危险因素之一.     

Polymorphism of methylenetetrahydrofolate reductase gene is associated with response to fluorouracil-based chemotherapy in Chinese patients with gastric cancer

Background The importance of polymorphisms in the methylenetetrahydrofolate reductase （MTHFR） gene for the prediction of the response to fluorouracil-based adjuvant chemotherapy in gastric cancer patients remains unclear. The aim of this study is to assess the predictive value of several polymorphisms of the MTHFR gene for clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population. Methods Three hundred and sixty-two Chinese patients with gastric cancer were treated with fluorouracil-based adjuvant chemotherapy. DNA samples were isolated from peripheral blood collected before treatment. The three single nucleotide polymorphisms （SNPs） （rs1801131, rs1801133, rs2274976） genotypes of the MTHFR gene were determined by matrix- assisted laser desorption/ionization time-of-flight mass spectrometry （MALDI-TOF MS）. Results The average response rate for chemotherapy was 46.7%. Homozygous genotypes rs2274976G/G （X2=22.7, P 〈0.01） and rs1801131A/A （X2=14.3, P=0.008） were over-represented in responsive patients. Carriers of the rs2274976A allele genotypes （G/A and A/A） and of the rs1801131C allele genotypes （A/C and C/C）were prevalent in nonresponsive patients. In the haplotype association analysis, there was a significant difference in global haplotype distribution between the groups （X2=20.69, P=0.000 124）. Conclusions These results suggest that polymorphisms of the MTHFR gene may be used as predictors of the response to fluorouracil-based chemotherapy for gastric cancer patients in Chinese population. Well-designed, comprehensive, and prospective studies on determining these polymorphisms of MTHFR gene as clinical markers for predicting the response to fluorouracil-based therapy in gastric cancer patients is warranted.     

The effects of smoking and drinking on all-cause mortality in patients with dilated cardiomyopathy: a single-center cohort study

Subject

Recent studies have shown that smoking and drinking are associated with poorer outcomes in patients with cardiomyopathy. The purpose of this study was to determine all-cause mortality in dilated cardiomyopathy (DCM) associated with smoking and drinking.

Methods

An observational cohort study was undertaken in DCM patients from November 2003 to September 2011. A total of 1118 patients were enrolled, with a mean follow-up of 3.5 ± 2.3 years. Standard demographics were obtained, and transthoracic echocardiography and routine blood testing were performed shortly after admission. Outcome assessment was based on the all-cause death after admission.

Results

The patients were divided into three groups: non-smokers (n = 593), mild-to-moderate smokers (n = 159) and heavy smokers (n = 366). The all-cause mortality rates showed no differences between the three groups (23.8, 20.8 and 24 %, respectively; log-rank χ² = 1.281, P = 0.527). There was also no significant difference in mortality between non-drinkers (n = 747), mild drinkers (n = 142) and moderate drinkers (n = 229) (23.7, 23.2 and 22.3 %, respectively; log-rank χ² = 2.343, P = 0.310). In the Cox analysis, neither the smoking (HR 0.971, P = 0.663) nor the drinking status (HR 0.891, P = 0.140) was a significant independent predictor of all-cause mortality in patients with DCM.

Conclusion

In conclusion, there were no significant differences in mortality between the smoking- and drinking-related patient groups, indicating no effect of smoking and drinking on all-cause mortality in patients with DCM in the present large-scale study.     

海南地区汉族人脂联素基因单核苷酸多态性与2型糖尿病的相关性研究

目的研究脂联素基因单核苷酸多态性（SNP45T→G和SNP276G→T）两个位点与海南地区汉族人2型糖尿病之间的关系。方法采用病例对照研究方法,以聚合酶链式反应—限制性内切酶长度多态性（PCR-RFLP）技术,对106例2型糖尿病患者和58例正常对照者脂联素基因SNP45、SNP276多态性位点进行基因分型。结果SNPS45和SNPS267两个多态性位点的基因型和等位基因频率在2型糖尿病组和正常对照组中的分布差异无统计学意义。各组中TG单倍型纯合携带者（TG／TG）与TG单倍型杂合携带者（TG／X）或未携带者（X／X）的体重指数比较差异均无统计学意义。结论脂联素基因的SNP45和SNP276多态性位点与海南地区汉族人群中2型糖尿病无明显相关性。     

上海地区汉族人群护骨素基因G1181C多态性与冠状动脉性心脏病及其严重程度的相关性

目的探讨护骨素基因G1181C位点单核苷酸多态性(SNPs)与冠状动脉性心脏病(CAD)及其严重程度的相关性。方法 368例胸痛患者根据冠状动脉造影检查结果分为非CAD组(146名)和CAD组(222例)。CAD组中单支、双支、三支、四支病变分别为72、59、77、14例。CAD组再根据病史分为急性冠状动脉综合征(ACS)组156例和稳定型CAD组66例。采用介质纯化法提取白细胞DNA,聚合酶链反应(PCR)扩增包含G1181C位点的DNA片段,连接酶检测反应(LDR)检测PCR产物,识别多态性位点。结果非CAD组与CAD组间,非CAD组与ACS组间,ACS组与稳定型CAD组间,非CAD组与不同病变冠状动脉数量组间,护骨素基因G1181C的各基因型频率和分布的差异均无统计学意义(P值均>0.05)。结论研究中未发现护骨素基因G1181C位点SNPs多态性与CAD及其严重程度相关。     

Back pain in patients with severe osteoporosis on teriparatide or antiresorptives: a prospective observational study in a multiethnic population

INTRODUCTION

We evaluated reduced back pain in a multiethnic population treated with teriparatide and/or antiresorptives in real-life clinical settings over 12 months.

METHODS

This prospective observational study comprised 562 men and postmenopausal women (mean age 68.8 years) receiving either teriparatide (n = 230), antiresorptives (raloxifene or bisphosphonates; n = 322), or both (n = 10) for severe osteoporosis. The primary endpoint was the relative risk of new/worsening back pain at six months.

RESULTS

At baseline, a higher proportion of teriparatide-treated than antiresorptive-treated patients had severe back pain (30.9% vs. 17.7%), extreme pain/discomfort (25.3% vs. 16.8%), extreme anxiety/depression (16.6% vs. 7.8%) and were confined to bed (10.0% vs. 5.3%). Teriparatide-treated patients had higher visual analog scale (VAS) scores for pain (5.8 ± 2.42 vs. 5.1 ± 2.58) and lower mean European Quality of Life-5 Dimensions (EQ-5D) scores (37.7 ± 29.15 vs. 45.5 ± 31.42) than antiresorptive-treated patients. The incidence of new/worsening back pain at six months for patients on teriparatide and antiresorptives was 9.8% and 10.3% (relative risk 0.99, 95% confidence interval 0.80–1.23), respectively. The incidence of severe back pain at 12 months was 1.3% and 1.6% in the teriparatide and antiresorptive treatment groups, respectively. Teriparatide-treated patients had lower mean VAS (2.71 ± 2.21 vs. 3.30 ± 2.37) and EQ-5D (46.1 ± 33.18 vs. 55.4 ± 32.65) scores at 12 months. More teriparatide-treated patients felt better (82.7% vs. 71.0%) and were very satisfied with treatment (49.4% vs. 36.8%) compared to antiresorptive-treated patients.

CONCLUSION

Patients treated with either teriparatide or antiresorptives had similar risk of new/worsening back pain at six months.     

Polymorphism of interleukin-17 and its relation to mineral density of bones in perimenopausal women

Background

Recognition of different genetic variants underlying osteoporosis would make it possible to introduce individual, symptomatic treatment as well as early prophylaxis of osteoporosis.The aim of the study was to evaluate the frequency of the rs2275913 (−197G > A) polymorphism of the IL-17 gene and assess the relation of this polymorphism with the clinical parameters of the osseous turnover and degree of the postmenopausal osteoporosis.

Methods

The study included 800 women of postmenopausal (505) and reproductive (295) ages throughout the Wielkopolska region in Poland. The postmenopausal group included women with osteoporosis and osteopenia, and those who were healthy. Women at reproductive age were healthy. The frequency of the tested gene polymorphism was evaluated in the group where bone mineral density (BMD) was marked and in the control group.

Results

The results obtained showed that the T-score in the female population with osteopenia was remarkably lower in women showing the GG genotype of -197G > A polymorphism of IL-17 gene compared to patients with heterozygous GA genotype. It has been shown that the BMD value for L2–L4 YA in the evaluated female population with osteoporosis is significantly higher in women with the GA genotype of -197G > A polymorphism of IL-17 gene compared to women with the GG genotype (76.32% versus 59.93%, P <0.05). It has also been noted that the BMD value for L2 to L4 AM in patients with the GG genotype was lower than in women with the AA genotype (69.73% versus 80.88%, P <0.05).

Conclusions

It is suggested that the -197G > A polymorphism of the IL-17 gene may be considered as a genetic factor of postmenopausal osteoporosis. This polymorphism can influence the bone mineral density and T-score value in young women and postmenopausal women.     

HSD17 B1和HSD17 B2基因多态性与四川汉族人群肝癌的关联性研究

目的：探讨性激素17β-羟甾类固醇脱氢酶（HSD17B1和HSD17B2）基因单核苷酸多态性与四川地区汉族人群肝癌之间的关系,为肝癌的预防、筛查、治疗及预后提供理论依据。方法以136例汉族肝癌患者,200例汉族健康人群为对象,选取HSD17B1 rs676387、HSD17B2 rs8191246两个位点作为遗传标志,采用聚合酶链反应-限制性片段长度多态技术检测 HSD17B1和 HSD17B2基因多态性及其分布频率。结果与健康人群相比HSD17B1 rs676387的T等位基因显著增加肝癌患病风险（P＜0．05）。结论 HSD17B1 rs676387与四川汉族 HCC的发生发展具有相关性,该研究结果有待在多民族、多中心、大样本研究中进一步证实。     

APPL1基因与2型糖尿病患者体脂含量及分布的相关性

目的 观察APPL1基因单核苷酸多态性(SNP)与体脂含量及分布的关系.方法 590例无血缘关系的上海地区中国人,糖耐量正常(NGT)者358名,2型糖尿病(T2DM)者232例.用聚合酶链反应-限制性片段长度多态性方法检测rs3806622、rs4640525基因型.测定体重指数(BMI)、腰围(W)、臀围和股围.测定空腹血脂谱、空腹及糖负荷后2 h血糖、胰岛素和C肽水平.结果 不论在NGT组还是T2DM组,其BMI＞25 kg/m2与BMI≥25 kg/m2亚组间rs3806622、rs4640525基因型频率和等位基因频率比较差异均无统计学意义;T2DM组腰围亚组问rs3806622、rs4640525等位基因频率分布差异有统计学意义(均P＜0.05),腰围值高者G等位基因频率显著增高[0.084,W＜90 cm(0.022)],OR值分别为2.26(95%可信区间1.05～4.86)和4.13(95%可信区间1.21～14.09);经年龄、性别、BMI校正后,T2DM组rs3806622、rs4640525位点携带G等位基因者均较非携带G等位基因者腰围值高(P＜0.05);相关因素的逐步多元回归分析发现性别、BMI及rs4640525均独立相关因素(均P＜0.05).结论 APPL1基因SNP(rs3806622和rs4640525)与中国人2型糖尿病患者体脂分布相关.     

A rare case of multiple bronchial artery aneurysms associated with a double aortic arch

Bronchial artery aneurysm is uncommon, and the occurrence of multiple aneurysms arising from a bronchial artery is even rarer. To date, there has been only one published case report describing double bronchial artery aneurysms. We herein describe a case of three aneurysms arising from a left bronchial artery, accompanied by multiple bilateral hypertrophied bronchial and intercostobronchial arteries, as well as a double aortic arch. Bronchial artery aneurysm is potentially life-threatening, and immediate treatment is recommended to minimise the potential risk of rupture. The aneurysms in our case were successfully treated via transcatheter arterial embolisation using coils.     

Gln192Arg polymorphism in paraoxonase 1 gene is associated with Alzheimer disease in a Chinese Han ethnic population

Background Oxidative stress such as low-density lipoprotein （LDL） oxidation is thought to be an important mechanism in Alzheimer＇s disease （AD）. Paraoxonase 1 （PON1）, an enzyme located on high-density lipoprotein, can prevent LDL from oxidation to some extent. It is also a potent cholinesterase inhibitor and an arylesterase, combating organophosphate poisoning and metabolization of environmental neurotoxins which might be responsible for neurodegeneration with aging.We evaluated the association of Gln192Arg polymorphism in the PON1 gene with AD in a Chinese Han ethnic population. Methods Patients and age-matched controls were recruited from outpatient clinics and a population-based epidemiological survey, respectively. Gln192Arg polymorphism in the PON1 gene was detected by allele-specific PCR technique in 521 patients with AD and 578 healthy controls. Results The presence of at least one of PON1 R alleles （Q/R or R/R） was lower in AD patients than in the controls （82.7% vs 87.4%; χ^2 = 4.68, P = 0.03）. PON1 gene R allele frequency was lower in AD patients than in the controls （60.7% vs 64.7%; χ^2=3.85, P = 0.05）. One-way ANOVA showed that PON1 genotype had no effect on the age of onset for developing AD. Logistic regression analysis demonstrated the age and sex-adjusted odds ratio （OR） for the risk of AD in PON1 of PON1 R allele carriers was 0.71 （P = 0.044, 95%CI, 0.51 - 0.99）. Conclusion Our results indicate that Gln192Arg polymorphism in the PON1 gene is associated with AD, and PON1 R allele might be a protective factor for AD in a Chinese Han ethnic population.     

Sleep-related breathing disorder is associated with hyperactivity in preschoolers

INTRODUCTION

Sleep problems are a prominent feature in children with attention deficit hyperactivity disorder (ADHD). Unlike existing studies that focused on extreme samples (i.e. normal vs. ADHD), our study investigated the associations of sleep-related behaviours and ADHD features in nonclinical Chinese preschoolers.

METHODS

All participants were recruited via advertisements and screened for eligibility through a telephone interview prior to an onsite visit. The maternal reports of the Conners’ Parent Rating Scale (CPRS) and Pediatric Sleep Questionnaire (PSQ) were acquired from 110 Chinese preschoolers aged six years. Regression models were used to examine the association between CPRS and PSQ scores.

RESULTS

The results obtained from regression models on the CPRS and PSQ scores of the 110 participants showed that none of the sleep-related behavioural measures (i.e. sleep-related breathing disorder [SRBD], snoring, daytime sleepiness, restless legs syndrome) was associated with inattention in our sample. However, worse SRBD was associated with higher hyperactivity.

CONCLUSION

Our study underpins the importance of understanding the relationship between sleep-related behaviours and ADHD characteristics before the usual age of clinical diagnosis in children with ADHD.     

PRM 2 G398C多态性与386例汉族男性生育力的相关性研究

目的：研究鱼精蛋白2（PRM2）基因 G398C多态性与汉族男性生育力的相关性。方法选取386例原发不育男性患者为观察组,255例生育男性为对照组,分别分析两组常规精液参数及DNA 完整性、核蛋白成熟度等精子功能参数,采用DNA测序技术对PRM 2 G398C位点进行基因分型,统计该多态性位点与男性不育发病率的关系。结果不育患者 PRM 2 G398C位点CC基因型频率（11．92％）高于生育男性（6．67％）,分析显示CC基因型与男性不育的遗传易感性明显相关（OR＝2．002,95％CI＝1．097～3．653,P＜0．05）。CC基因型可使精子DNA完整性、核蛋白成熟度等精子功能参数明显下降,可能是其导致男性不育的主要因素。结论 PRM 2 G398C多态性改变与汉族男性生育力相关。