白介素-18基因启动子-607C／A多态性与缺血性脑卒中的相关性

目的：阐明白介素-18（IL-18）与缺血性脑卒中（IS）的相关性。方法：采用病例对照研究方法,对IS病例组423例和对照组384名（两组研究对象年龄、性别匹配,均为中国汉族人群）应用聚合酶链反应技术（PCR）及凝胶电泳技术进行IL-18基因启动子-607C／A（rs1946518）分析。用Logistic回归分析去除混杂因素的影响,分析其基因型、等位基因型与缺血性脑卒中发病的相关性。结果：-607C等位基因型与IS发病有相关性,是IS重要的危险因素（OR=I．358,P=0．002）。结论：中国汉族人群中,IL-18基因启动子的多态性可能与IS的发病有关,等位基因型-607C可能增加IS的发病风险。     

Interleukin-18 promoter polymorphisms and risk of ischemic stroke

Ischemic stroke (IS) is a major cause of morbidity and mortality around the world. Interleukin-18 (IL-18) plays an important role in the pathogenesis of IS and IL-18 promoter polymorphisms have been shown to be associated with levels of expression of IL-18. We investigated the association of two functional polymorphisms in IL-18 promoter, −607C/A (rs1946518) and −137G/C (rs187238), with the risk of ischemic stroke in a Han Chinese population of 423 patients and 384 healthy controls matched for sex and age. The results revealed that the −607C allele was associated with an increased risk of IS with an odds ratios (OR) of 1.358 (P = 0.002, power = 100%) and the presence of the −137G allele was correlated with increased the risk of IS in the subtype of patients with large artery atherosclerosis (LAA) (OR = 1.583, P = 0.02, power = 94%). Patients with the −607C/−137G haplotype also had significantly increased risk of IS compared to controls (OR = 1.341, P = 0.005, power = 100%). Our findings suggest that these functional polymorphisms in the IL-18 promoter are involved in development of IS in the Han Chinese population.     

Genetic relationship between serum pregnancy-associated plasma protein-A gene polymorphism and ischemic cerebrovascular disease in a Northern Han Chinese population

The present study recruited 193 patients with ischemic cerebrovascular disease from Inpatient and Outpatient Departments at the Affiliated Hospital of Qingdao University Medical College, China from August 2008 to May 2010, as well as 120 healthy volunteers from the Medical Examination Center at the Affiliated Hospital of Qingdao University Medical College, China, who served as controls for this study. Patients and control subjects were from the Han population in northern China. Enzyme- linked immunosorbent assay analysis revealed increased levels of serum pregnancy-associated plasma protein-A (PAPP-A) in ischemic cerebrovascular disease patients compared with healthy controls. In addition, the patients exhibited greater frequency of genotype CC and C alleles in a missense A/C (Tyr/Ser) polymorphism (dbSNP: rs7020782) of exon 14 in the PAPP-A gene. Multiple-factor logistic regression analysis on correction of age, gender, history of smoking, hypertension, diabetes mellitus, hypercholesteremia, and ischemic stroke family history showed that the risk for ischemic cerebrovascular disease in the population without the A allele at the A/C genetic locus in exon 14 of the PAPP-A was 2-folds greater than the population expressing the A allele. These experimental findings suggested that ischemic cerebrovascular disease correlated with the C allele in exon 14 of PAPP-A. In addition, the A allele is likely a protective gene; individuals carrying the A allele were less prone to ischemic cerebrovascular disease compared with individuals without the A allele.     

白介素-18基因启动子多态性与阿尔茨海默病的关联分析

目的 探讨IL-18基因启动子区位点单核苷酸多态性与散发性阿尔茨海默病(SAD)的相关关系.方法 采用病例对照的研究方法,共入选SAD患者109例和同期年龄、性别完全匹配的对照组109例.应用序列特异性引物-聚合酶链反应技术检测两组对象IL-18基囚启动子-607C/A位点单核苷酸多态性.结果 IL-18基囚启动子-607C/A位点等位基因和基因型分布在SAD组和对照组间比较差异有统计学意义(P=0.021,P=0.041).SAD组-607CC基因型分布频率明显高于对照组,比较差异有统计学意义(x2=4.109,P=0.043),携带-607CC基因型的人群患SAD的风险是非携带人群的1.90倍(OR=1.90,95%CI:1.017～3.550).结论 SAD与IL-18基因启动子-607C/A位点单核苷酸多态性相关,其中-607CC基因型的人群发生SAD的风险较其他基因型人群的风险高.     

BDNF基因启动子区多态性与散发性阿尔茨海默病的相关性研究

目的研究脑源性神经营养因子(BDNF)基因启动子区单核苷酸多态性与散发性阿尔茨海默病(SAD)发病的相关性。方法随机选取10例正常对照组及10例SAD患者进行BDNF基因启动子区-1～-2812bp测序,针对所发现的启动子区单核苷酸多态性(SNP),利用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)的方法对328例正常对照者及292例SAD患者进行基因型检测后进行病例-对照关联分析。结果在中国北方汉族人群的BDNF基因启动子区发现1个SNP:-2467G/A(rs908867)。其等位基因及基因型分布在两组间无显著性差异(P值分别为0.10和0.27),经APOEε4分层后它们的分布在两组间也无显著性差异(P>0.05)。结论中国北方汉族人群BDNF基因启动子区的遗传变异可能与SAD发病无关。     

脂联素基因单核苷酸多态rs266729、 rs2241766、rs822396与老年缺血性 脑血管病亚型相关性研究

目的 探讨中国北方青岛地区汉族人群脂联素（adiponectin,ADIPOQ）基因多态性与老年缺血性脑血
管病发病的相关性。
方法 入组年龄大于60岁的老年缺血性脑血管病患者,按急性卒中治疗低分子肝素试验（Trial
of Org 10172 in Acute Stroke Treatment,TOAST）分型,选取大动脉粥样硬化性（large artery
atherosclerosis,LAA）和小动脉闭塞性（small artery occlusion,SAO）两种亚型患者,其中LAA 144例,
SAO 221例;402例同期查体者进行病例对照研究。对比两组的ADIPOQ基因多态性。
结果 rs266729（-11377C/G）的基因型分布在LAA组、SAO组与对照组3组中有显著差异（P =0.036）。
3组中两两比较显示,SAO组中rs266729（-11377C/G）GG基因型分布显著高于对照组（P =0.009）;在
隐性［P =0.004,比值比（odds ratio,OR）=2.478,95%可信区间（confidence interval,CI）=1.31～4.70］、
累加模式（P =0.003,OR 2.680,95%CI 1.39～5.15）下,rs266729（-11377C/G）基因型分布在SAO组与
对照组中也有显著差异,G 等位基因能增加SAO型缺血性脑血管病的风险,但在显性模式下差异无显
著性。rs822396（-3964A/G）、rs2241766（-45T/G）的基因型分布在LAA组、SAO组与对照组3组中均
无显著差异。
结论 rs266729（-11377C/G）G 等位基因与老年缺血性脑血管病发病相关,其G 等位基因变异可增
加老年患者SAO型缺血性脑血管病的风险。     

Fibroblast growth factor 20 (FGF20) polymorphism is a risk factor for Parkinson's disease in Chinese population

The etiology of Parkinson's disease (PD) is not well established. Genetic variation in fibroblast growth factor 20 (FGF20) might influence the risk of PD occurrence and development. In this study, Two DNA polymorphisms at genetic variation in FGF20, rs2720208 (C/T) and rs1721100 (C/G), were genotyped by direct sequencing in Han Chinese population, including 394 PD patients and 383 healthy controls. Statistical analyses revealed that for rs1721100 (C/G) polymorphism, there were significant differences in genotype distribution between PD and healthy-matched controls. For rs12720208 (C/T) polymorphism, there was no significant difference in genotype distribution and gender and age-related differences between PD and control group. Results in this study revealed that the rs1721100(C/G) polymorphism is a risk factor for PD in Han Chinese population, while rs12720208(C/T) polymorphism is not significantly associated with PD.     

The relationship between ADAM17 promoter polymorphisms and sporadic Alzheimer’s disease in a Northern Chinese Han population

The deposition of amyloid beta peptides (Aβ) in the brain is crucial in the pathogenesis of Alzheimer’s disease (AD). A disintegrin and metalloproteinase (ADAM) 17 cleaves the amyloid precursor protein (APP) within the Aβ sequence and, therefore, precludes the formation of neurotoxic Aβ. To explore the correlation between the ADAM17 promoter and sporadic AD (SAD), a case-control study was conducted in a Northern Chinese Han population. The ADAM17 gene promoter region was screened, resulting in five known and one novel single nucleotide polymorphisms (SNP): ?1672C/T (rs11689958), ?1638T/G (rs1524668), ?1437T/C (rs11684747), ?1333C/T (rs12474969), ?172T/C (rs12692386) and ?154C/A. Using direct sequencing, genotypes were determined in 403 patients who had SAD and 323 control participants. No association was observed between these polymorphisms and SAD. These data indicated that, in a Northern Chinese Han population, SNP in the ADAM17 promoter do not influence the risk of SAD.     

神经肽Y基因启动子多态性与缺血性脑卒中的相关性研究

目的：探讨神经肽Y（NPY）基因启动子多态性与缺血性脑卒中的相关性。方法：采用聚合酶链反应（PCR）及基因测序技术,对450例缺血性脑卒中患者及423名正常对照者NPY基因启动子-399T／C（rs16147）基因型及等位基因频率进行检测。Logistic回归分析去除混杂因素影响,分析其与缺血性脑卒中发病的相关性。结果：脑卒中组NPY基因型和等位基因频率与正常对照组比差异有显著统计学意义,特别是在小动脉闭塞性脑卒中类型中。-399C等位基因与缺血性脑卒中存在相关性,是其重要危险因素（OR=2．398,95％CI=1．036-5．553,P=0．041）。结论：NPY基因启动子多态性可能与缺血性脑卒中的发病存在相关,具有-399C等位基因的个体发生缺血性脑卒中的风险可能显著增加。     

β-分泌酶2多态性位点rs2252576与散发性阿尔茨海默病的相关性分析

目的 研究β-分泌酶2（BACE2） rs2252576位点基因多态性与中国北方汉族人群散发性阿尔茨海默病（SAD）发病的相关性.方法 随机选取10例SAD患者和10名健康对照者进行BACE2外显子区测序.筛查出第5外显子上游10bp存在一多态性位点rs2252576C/T,随后对348例SAD患者和294名健康对照者进行多态性分型及统计学分析.结果 SAD患者和健康对照组的BACE2基因rs2252576多态性位点基因型和等位基因频率差异无统计学意义（P＞0.05）.根据是否携带ApoEε4等位基因进行进一步分层比较后,该位点差异仍无统计学意义（P＞0.05）.应用Logistic回归分析平衡了年龄、性别和ApoE分型的影响后,差异仍无统计学意义（P＞0.05）.结论 中国北方汉族人群中BACE2基因rs2252576 C/T位点的基因多态性与SAD的发病可能无关.     

自噬相关基因5(Atg5)标签单核苷酸多态性与帕金森病的相关性研究

目的探讨中国粤西地区汉族人群自噬相关基因5(autophagy-related gene 5,Atg5)标签单核苷酸多态性(TagSNP)rs17587319C/G多态性与帕金森病(PD)的关系。方法采用病例-对照研究,应用聚合酶链反应-限制性酶切片段长度多态性分析方法(PCR-RFLP)检测80例PD患者(病例组)和87例健康对照者(对照组)的Atg5基因Tag SNP rs17587319C/G多态。结果病例组CC基因型为78.7%,对照组为58.6%,差异有统计学意义(P=0.005,OR=2.62,95%CI:1.32～5.19);C等位基因频率在病例组和对照组分别为89.4%和74.7%,差异有统计学意义(P=0.001,OR=2.85,95%CI:1.55～5.23);对照组中发现8例Atg5基因Tag SNP rs17587319C/G的GG纯合子,而在病例组中未发现。结论 Atg5基因TagSNP rs17587319C/G的C等位基因与CC基因型可能是PD的危险因素。     

Association of ALOX15 Gene Polymorphism with Ischemic Stroke in Northern Chinese Han Population

Arachidonate 12/15-lipoxygenase (12/15-LOX) is a member of the lipid peroxidizing enzyme family and plays a major role in atherosclerosis. The present study aimed to evaluate whether or not the ALOX15 gene polymorphism is involved in ischemic stroke in northern Chinese Han population. Participants in a case-control study included 396 patients (239 males, 157 females) with ischemic stroke and 360 healthy subjects (211 males, 149 females). The rs7217186 polymorphism of the ALOX15 gene was analyzed by polymerase chain reaction and restriction fragment length polymorphism, while the rs2619112 polymorphism of the ALOX15 gene was analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The frequencies of the CC genotype and the C allele of rs7217186 were higher in participants with ischemic stroke than in the control group [P?=?0.014 in males, P?=?0.007 in atherosclerosis ischemic stroke (ACI)]. The frequencies of the AA genotype and the A allele of rs2619112 were higher in participants with ischemic stroke than in the control group (P?=?0.011 in males, P?=?0.015 in ACI). Multiple logistic regression analysis revealed the significance of rs7217186 and rs2619112 in males and in ACI after adjustment for confounding factors. The rs7217186 and rs2619112 polymorphisms of the ALOX15 gene were associated with ischemic stroke in males and in patients with ACI in northern Chinese Han population.     

Association between Histone Deacetylase 9 Gene Polymorphism and Stroke in Chinese Han Population

ObjectiveTo explore the correlation between the polymorphism of histone deacetylase 9 gene (rs1060499865, rs723296, rs957960) and ischemic stroke (IS) in Chinese Han population in Dali region. MethodsThis study included 155 IS patients and 128 healthy physical examinees. TaqMan-polymerase chain reaction technology and multivariate logistic regression were performed. ResultsIn the case group, there was no polymorphism of rs1060499865 observed in the two groups; whereas on the rs723296 locus the frequencies of C allele and TC genotype were significantly higher than that in the control group, alleles C and T were associated with a 2.158-fold increase in IS risk, and genotypes TC and TT were associated with a 2.269-fold increase in IS risk. The locus rs957960 exhibited no significant difference between the two groups. ConclusionAn association between rs723296 and the risk of IS was found in the Chinese Han population in Dali region. No significant association was found between rs1060499865, rs957960 and IS in the Chinese Han population in Dali region.     

缺血性脑卒中患者的IL-18表达水平及其基因105A/C多态性与肺炎衣原体感染的相关性研究

目的探讨缺血性脑卒中患者体内IL-18表达水平的变化及其基因105A/C多态性与缺血性脑卒中疾病的相关性。方法选择55例缺血性脑卒中患者为实验组,55例健康体检人群为对照组,收集全血标本后用ELISA检测试剂盒分别测定标本的血浆中Cpn IgA、Cpn IgG抗体水平及IL-18表达水平。应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术对IL-18基因105位点进行基因分型。结果 AIS组Cpn IgA阳性率明显高于健康对照组(χ~2=18.18,P0.05),而Cpn IgG阳性率二者无显著性差异。AIS组的IL-18表达水平明显高于健康对照组,且Cpn IgA阳性的AIS患者的IL-18表达水平高于Cpn IgA阴性患者,但其基因105A/C基因多态性比较无统计学意义。结论缺血性脑卒中的发生、发展与肺炎衣原体慢性感染和IL-18水平有关,和IL-18的105A/C基因多态性无明显相关,但具体作用机制还有待进一步研究。     

NOS2A基因启动子区基因多态性与缺血性脑卒中关系的研究

目的以SNPs为遗传标记,探讨NOS2A基因多态性与缺血性脑卒中的关系。方法以NOS2A启动子区-969G/C,-1173C/T的两个位点为遗传标记,通过对NOS2A基因启动子区进行全长测序以分析这两个位点的基因型。结果 -969G/C,-1173C/T不是中国北方汉族人的SNP位点,NOS2A-969C位点的等位基因均为T,NOS2A-1173C位点的等位基因均为G。我们在NOS2A基因启动子区检测到了rs2779248位点,关联分析表明rs2779248位点与缺血性脑卒中无相关性。结论 NOS2A基因启动子区与缺血性脑卒中的发病无明显相关。     

5-羟色胺2A受体基因-1438A/G多态性与抑郁症的关联研究

目的探讨中国汉族人群中抑郁症患者与5-羟色胺2A(5-HT2A)受体基因-1438A/G多态性之间的关系。方法采用高温连接酶检测反应法,检测254例抑郁症患者和231例正常对照者的5-HT2A受体基因-1438A/G多态性的基因型和等位基因分布。结果(1)5-HT2A受体基因-1438A/G多态性的基因型和等位基因频率在患者组和对照组的分布差异无统计学意义(P>0.05)。(2)患者组-1438A/G多态性的三种基因型之间的汉密尔顿抑郁量表总分和各因子分的差异无统计学意义(P>0.05)。(3)-1438A/G多态性基因型及等位基因在性别和有无精神病疾病家族史之间无显著差异(P>0.05)。结论在中国汉族人群中未发现5-HT2A受体基因-1438A/G多态性与抑郁症存在关联。     

Association of GWAS-Reported Variant rs11196288 near <Emphasis Type="Italic">HABP2</Emphasis> with Ischemic Stroke in Chinese Han Population

A recent genome-wide association analysis identified a novel single nucleotide polymorphism locus on chromosome 10q25.3 (rs11196288, near HABP2) associated with the risk of early-onset ischemic stroke (IS) in European population, but not with late-onset IS. However, the role of this genome-wide association study (GWAS)-reported variant in ischemic stroke in Chinese Han population remained unknown. In our study, 389 adult ischemic stroke patients with an age of onset <60 years and 389 matched healthy controls were enrolled to investigate association of rs11196288 genotypes with early-onset ischemic stroke and its subtypes; the association was further examined in another independent population consisting of 349 ischemic stroke patients with an age of onset ≧60 years and 349 matched healthy individuals. Logistic regression analysis showed no significant association between rs11196288 and early-onset ischemic stroke (IS), large artery atherosclerotic (LAA) stroke, or small vessel disease (SVD) stroke (all P > 0.050). Nevertheless, in subgroup analysis of the older population, rs11196288 presented significant effect on late-onset SVD stroke susceptibility in the dominant model (GG/GA vs AA, OR 1.70; 95%CI 1.02 to 2.85; P = 0.042). The results indicated that the role of rs11196288 polymorphism in ischemic stroke susceptibility in Chinese Han population may be different from that in European. Larger studies with diverse populations are warranted to confirm and extend our findings.     

The functional SNP rs4376531 in the ARHGEF gene is a risk factor for the atherothrombotic stroke in Han Chinese

The gene encoding RhoA guanine nucleotide exchange factor 10(ARHGEF10) has been reported to be a risk factor for atherothrombotic stroke (AS) in Japanese. The single-nucleotide polymorphism (SNP) rs4376531 in intron 16 on ARHGEF10 is associated with AS and may play a role in the disease pathology. In order to explore the nature of this association in greater detail and in a new ethnic group, we carried out a case-control study to determine whether the rs4376531 polymorphism in ARHGEF10 is a risk factor of AS in Han Chinese people. This study was carried out to assay the frequency of genotypes and alleles of SNP rs4376531 in ARHGEF10 in patients with ischemic stroke and healthy controls using the polymerase chain reaction and the restriction fragment length polymorphism (PCR-RFLP) technique. A total of 383 individuals with AS in West China Hospital and 214 unrelated healthy controls were recruited. The frequencies of the G allele and GG genotype of the rs4376531 polymorphism were higher in the patients with AS than in control individuals: frequency of G, 91.0% vs 83.4%, P<0.001; GG, 82.2% vs 67.8%, P<0.001. After adjusting for sex, age, and multiple cardiovascular risk factors, the homozygous GG genotype for this variant was associated with a higher risk of AS, with an adjusted odds ratio of 4.99 (95% CI, 2.55-7.81, P< 0.001). Our findings suggest that the rs4376531 polymorphism in the ARHGEF10 gene is a risk factor for AS in the Han Chinese population.     

血管内皮生长因子基因启动子区多态与散发性阿尔茨海默病的关系

目的 研究血管内皮生长因子(vascular endothelial growth factor,VEGF)基因启动子区多态与散发性阿尔茨海默病(sporadic Alzheimer's disease,SAD)发病的关系.方法 用聚合酶链反应.限制性片段长度多态性(PCR-RFLP)或直接测序的方法对北方汉族279例SAD患者和317名健康对照者进行多态分型.采用SPSS 11.5统计学软件包进行等位基因和基因型分布的比较及其与疾病的关联分析.结果 北方汉族人群中VEGF启动子存在3个多态位点:-2578C/A(rs699947)、-2549I/D(rs35569394)和-1154G/A(rs1570360),其中-2549I/D位点为18个碱基的插入或缺失.-2578C/A和-2549I/D存在显著的连锁不平衡,当-2578为A等位基因时,-2549I/D位点有18个碱基的插入,而当-2578是C纯合子时,-2549I/D位点则为18个碱基的缺失.这3个多态位点的基因型频率、等位基因频率以及单体型分布在SAD患者和对照组间差异无统计学意义.用Logistic回归校正年龄、性别和ApoE状态后,-1154G/A的GG基因型增加了SAD的发病风险.在不携带ApoE ε4的亚组中,单体型-2549D/-1154G可能增加SAD的发病风险(OR=1.325,95%CI1.023～1.716,P=0.033).结论 北方汉族人群中VEGF启动子存在3个多态位点-2578C/A、-2549I/D和-1154G/A.-1154G/A的GG基因型增加了SAD的发病风险.在不携带ApoE ε4的情况下,VEGF启动子的-2549D/-1154G单体型可能是SAD发病的危险因素.     

白细胞介素-6基因-174G/C多态性与阿尔茨海默病及血管性痴呆的关联研究

目的 探索白细胞介素-6(IL-6)基因启动子区-174G/C多态性与阿尔茨海默病(AD)、血管性痴呆(VD)的关系.方法 采取病例对照研究方法 ,以广州地区流行病学调查中诊断的161例AD、54例VD患者和247名健康老年人为研究对象,用聚合酶链反应-限制性片段长度多态性技术检测IL-6基因-174G/C多态性.结果 (1)所有研究对象均无C/C基因型.(2)AD组C等位基因频率(0.9%)及G/C基因型(1.9%)高于正常对照组(均为0),但差异无统计学意义(P＞0.05);按是否携带载脂蛋白E(Apo E)ε4进行分层,差异仍无统计学意义(P＞0.05).(3)VD患者C等位基因(1.9%)频率及G/C基因型(3.7%)高于正常对照组(均为0),差异有统计学意义(均P＜0.05).(4)中、重度AD患者含ε4等位基因的频率(23.9%)高于对照组(14.7%,P＜0.05).结论 IL-6基因-174G/C多态性不是广州地区汉族人群AD发病的危险因素,但与VD可能有关联.