胆固醇结石患者固醇携带蛋白2基因单核苷酸多态性的检测

目的:检测胆固醇结石患者和非胆石患者固醇携带蛋白2(SCP2)基因单核苷酸多态性(SNP),并探讨SNP与胆固醇结石的关系.方法:应用聚合酶链式反应-单链构象多态性(PCR-SSCP)银染技术并结合DNA直接测序,检测了58例散发胆固醇结石病人和50例非胆石病人SCP2基因的部分启动子区、全部编码区及部分3,未翻译区序列.结果:SCP2基因第14外显子检出变异DNA单链泳动条带.58例散发胆固醇结石病人中共有31例检测出变异DNA单链泳动带,突变率为53.45%;而50例非胆石病人仅有7例检测到变异泳动带,突变率为14.00%;两组突变率差异有显著性(x2=20.123,P＜0.001).部分病例pCR产物直接测序发现G284→A碱基颠换,为同义突变.结论:SCP2基因 284位点突变不影响SCP2蛋白的结构和功能,但G284→A的基因型频率在胆固醇结石患者较非胆固醇结石病人为高,有一定的诊断参考价值.     

外源性一氧化氮对骨肉瘤细胞株HOS生长能力的影响

目的：研究外源性一氧化氮对骨肉瘤细胞株（ＨＯＳ）体外生长能力的影响。方法：用不同浓度的ＳＮＰ（Ｓｏｄｉｕｍ Ｎｉｔｒｏｐｒｕｓｓｉｄｅ,硝普纳）作用于体外培养的ＨＯＳ细胞株,经细胞作用产生外源性一氧化氮,通过Ｇｒｉｅｓｓ比色法、ＭＴＴ比色法,观察ＨＯＳ细胞株一氧化氮的产生量及对细胞株生产情况的影响。结果：随着ＳＮＰ浓度的增加,ＨＯＳ细胞一氧化氮的产生量逐渐增加而细胞存活数量逐渐减少,以ＳＮＰ２００     

异丙酚对鼠小脑cGMP的作用

目的：全麻药可抑制中枢兴奋性突触传递，ＮＯ－ｃＧＭＰ系统在兴奋性突触传递中起秣和本研究旨在探讨异丙酚对鼠小脑内Ｎ－ｃＧＭＰ通路有无抑制及可能的作用位点。方法：将生后７天的幼鼠制成０．４ｍｍ厚度的切片，浸泡在Ｒｒｅｂｓ－Ｒｉｎｇｅｒ缓冲液内，行用异丙酚１ｍＭ、０．１ｍＭ或１０μＭ处理２０ｍｉｎ，再分别用ＮＭＤＡ、谷氨酸或硝普钠刺激３ｍｉｎ，快速置于液氮中固定保存。用放免法测定ｃＧＭＰ含量。结果：１ｍ     

Genetic variations in genes involved in testosterone metabolism are associated with prostate cancer progression: A Spanish multicenter study

BackgroundProstate cancer (PCa) is an androgen-dependent disease. Nonetheless, the role of single nucleotide polymorphisms (SNPs) in genes encoding androgen metabolism remains an unexplored area.PurposeTo investigate the role of germline variations in cytochrome P450 17A1 (CYP17A1) and steroid-5α-reductase, α-polypeptides 1 and 2 (SRD5A1 and SRD5A2) genes in PCa.Patients and methodsIn total, 494 consecutive Spanish patients diagnosed with nonmetastatic localized PCa were included in this multicenter study and were genotyped for 32 SNPs in SRD5A1, SRD5A2, and CYP17A1 genes using a Biotrove OpenArray NT Cycler. Clinical data were available. Genotypic and allelic frequencies, as well as haplotype analyses, were determined using the web-based environment SNPator. All additional statistical analyses comparing clinical data and SNPs were performed using PASW Statistics 15.ResultsThe call rate obtained (determined as the percentage of successful determinations) was 97.3% of detection. A total of 2 SNPs in SRD5A1—rs3822430 and rs1691053—were associated with prostate-specific antigen level at diagnosis. Moreover, G carriers for both SNPs were at higher risk of presenting initial prostate-specific antigen levels>20 ng/ml (Exp(B) = 2.812, 95% CI: 1.397–5.657, P = 0.004) than those who are AA-AA carriers. Haplotype analyses showed that patients with PCa nonhomozygous for the haplotype GCTTGTAGTA were at an elevated risk of presenting bigger clinical tumor size (Exp(B) = 3.823, 95% CI: 1.280–11.416, P = 0.016), and higher Gleason score (Exp(B) = 2.808, 95% CI: 1.134–6.953, P = 0.026).ConclusionsSNPs in SRD5A1 seem to affect the clinical characteristics of Spanish patients with PCa.     

X射线损伤修复交叉互补基因1的单核苷酸多态性与散发性结直肠癌易感性相关

目的 检测单核苷酸多态性（SNP）位点Arg399Gln在散发性结直肠癌患者和非癌对照组中的分布情况，分析其与散发性结直肠癌及其临床病理特征的相关性。方法 从178例肿瘤组织和非癌对照组的180例血样中提取DNA，采用Taqman探针技术检测Arg399Gln多态性表型，并用统计软件计算各基因型的比值比（OR）和95％可信区间（95％CI）。结果 肿瘤组与对照组就XRCC1Arg399Gln多态性的基因表型差异有统计学意义（P〈0．05）；年龄不超过60岁的患者和超过60岁的患者在该位点的基因型差异有统计学意义（P〈0．05）；以399Arg／Arg基因型为参照，在年龄超过50岁的人群中（OR=0．64，95％C10．50～0．83，P〈0．05）和男性人群中（OR=0．64，95％C10．51～0．79，P〈0．05）携带至少一个Gin等位基因可致罹患散发性结直肠癌的风险显著降低；XRCC1399SNP与患者性别及散发性结直肠癌的发生部位、Dukes分期、浸润深度、淋巴结转移以及病理分型均无显著相关性（P均〉0．05）。结论 XRCC1399SNP可能通过改变DNA的损伤修复功能，成为散发性结直肠癌的易感因素。     

The growth differentiation factor 5 (GDF5) core promoter polymorphism is not associated with knee osteoarthritis in the greek population

Genetic factors have been shown to play an important role in the etiology of osteoarthritis (OA). A functional single nucleotide polymorphism (SNP) +104T/C; rs143383 in the 5′ UTR of the GDF5 gene was recently associated with susceptibility to osteoarthritis in the Japanese and Chinese population. Our objective was to assess whether this SNP was also associated with knee OA in a Greek Caucasian population sample. The +104T/C SNP was genotyped in a total of 519 case–control cohort; 251 patients with idiopathic knee OA and 268 controls were used. No significant differences were found in genotype or allele frequencies of the +104T/C SNP of GDF5 gene between cases and controls (p < 0.05). Also, no significant differences in allelic and genotypic frequencies were found when the individuals were stratified by sex. Our data implied that the +104T/C; rs143383 GDF5 core promoter polymorphism is not a risk factor for OA etiology in Greek Caucasians. Our study highlights the heterogeneous nature of OA genetic susceptibility. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J. Orthop Res 26:136–140, 2008     

Sequence variation in alpha-methylacyl-CoA racemase and risk of early-onset and familial prostate cancer

BACKGROUND: Expression of the alpha-methylacyl-CoA racemase (AMACR) gene has been established as a sensitive and specific biomarker for the diagnosis of prostate cancer. An initial study has also suggested that the risk of familial (but not sporadic) prostate cancer may be associated with germline variation in the AMACR gene. METHODS: In a study of brothers discordant for the diagnosis of prostate cancer (including 449 affected and 394 unaffected men) from 332 familial and early-onset prostate cancer families, we used conditional logistic regression and family-based association tests to investigate the association between prostate cancer and five single nucleotide polymorphisms (SNPs) tagging common haplotype variation within the coding and regulatory regions of AMACR. RESULTS: The strongest evidence for prostate cancer association was for SNP rs3195676, with an estimated odds ratio of 0.58 (95% confidence interval = 0.38-0.90; P = 0.01 for a recessive model). This non-synonymous SNP (nsSNP) results in a methionine-to-valine substitution at codon 9 (M9V) in exon 2 of the AMACR gene. Three additional nsSNPs showed suggestive evidence for prostate cancer association (P < or = 0.10). CONCLUSIONS: Our results confirm an initial report of association between the AMACR gene and the risk of familial prostate cancer. These findings emphasize the value of studying early-onset and familial prostate cancer when attempting to identify genetic variation associated with prostate cancer.     

Association of HER-2 polymorphism with Japanese sporadic prostate cancer susceptibility

BACKGROUND: Genetic polymorphisms may affect the development of prostate cancer (Pca). HER-2 is a proto-oncogene that has an important role in many human cancers, including Pca. To determine the association of the HER-2 gene with Japanese sporadic Pca, we analyzed the frequency of codon 655 (A/G, isoleucine, or valine) in case and control group. METHODS: We genotyped Ile 655 Val in Pca patients (n = 285) and in matched controls (n = 233). Statistical analyses were performed by Fisher's exact test and logistic regression analysis. RESULTS: We observed a significantly lower frequency of the Val655 allele in the Pca patients (14.7%) compared to the control group (26.2%) (P = 0.0025, odds ratio (OR) = 0.476, 95% CI = 0.306-0.740). This SNP was not found to be correlated with clinical stage, PSA level, Gleason score of biopsies or age at diagnosis. CONCLUSIONS: Our results indicate that the frequency of Val655 in HER-2 was significantly lower in Japanese Pca patients, however, it was recently reported that Val655 was significant higher in breast cancer patients. This contradictory observation in prostate and breast cancer patients is interesting considering the opposite hormonal sensitivity of these two cancers.     

硝普钠控制性降压对脑脊液和血中乳酸浓度的影响

将颅脑手术２４例分成两组：硝普钠降压组１１例，正常对照组１３例，检测脑脊液和动脉血中乳酸含量，观察其变化，厂解控制性降压６０分钟，血压恢复后６０分钟及正常手术对脑及全身代谢的影响。结果显示：二组在手术（降压）各阶段，脑脊液、动脉血中乳酸变化及其比较均无差异（Ｐ＞０．０５），说明颅脑手术期间控制性降压６０分钟对脑及全身代谢诸方面是安全的。这可能与麻醉药降低脑及全身的代谢、吸入气氧浓度提高及脑血流的自动调节机制不受破坏有关。     

食管癌与O~6-甲基鸟嘌呤-DNA甲基转移酶基因多态性的关系

目的 探讨O~6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)基因多态性与新疆哈萨克族食管癌的关系.方法 应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测160例新疆哈族样本(51例食管鳞状细胞癌及109例对照)的MGMT基因5个单核苷酸多态性(SNPs)的基因型.结果 Promoter 485C>A等位基因在两组间的分布经Logistic模型计算,差异有统计学意义(P<0.05);5个SNPs联合分析,0突变等位基因和1～10突变等位基因在两组间的差异有统计学意义(P<0.05).结论 MGMT基因Promoter 485C>A与新疆哈族食管癌相关;5个SNPs的联合作用与新疆哈族食管癌相关,突变等位基因增加了患食管癌的病风险.     

Family-based association study of ROR2 polymorphisms with an array of radiographic hand bone strength phenotypes

Summary For the first time the study provides evidence of association of radiographic hand bone length (BL) and bone mineral density (BMD) with polymorphisms in ROR2 gene that plays important role in skeletal development. This contributes to better understanding of bone physiology and may have application in clinical practice. Introduction and hypothesis Bone size and bone mineral density (BMD) are major determinants of bone strength. Identification of genes affecting these traits’ variability is important for better understanding of normal and pathological bone physiology and identification of the individuals at risk for bone fracture. This study tested the hypothesis of association of radiographic hand bone length (BL) and BMD with polymorphisms in ROR2 gene that is important in skeletal development. Methods Nineteen ROR2 SNPs were genotyped in 705 individuals, belonging to 212 nuclear families. The four tagging SNPs (tSNPs) and the pairwise haplotypes between adjacent tSNPs were tested for association with series of hand BL and BMD measurements, adjusted for covariates, using family-based association tests. Results We observed significant associations with BL and BMD mean values for all 18 studied hand bones (p = 0.0080, 0.0030), mean BL and BMD for proximal phalanges (p = 0.0218, 0.0060) and metacarpal bones (p = 0.0014, 0.0004). In the latter, the association remained significant after correction for multiple testing. Conclusions The region of the first through the second ROR2 introns is most likely to contain the functional polymorphism/s responsible for the observed associations. Further studies are required to identify the ROR2 functional polymorphism/s affecting bone size and BMD variation.     

硝酸甘油、硝普钠、三磷酸腺苷三种药物用于控制性降压的临床比较

36例择期手术术中需行控制性降压的病人随机分成三组,其中 TNG 组12例,SNP 组11例,ATP 组13例。降压期间观察到的各项变化有:MAP 分别比降压前下降26.01％(TNG)、28.42％(SNP)和30.57％(ATP);SV 分别减少24.42％(TNG,P<0.05)和28.15％(SNP,P<0.001);HR 分别增快21.20％(TNG,P<0.001)和21.60％(SNP,P<0.001);ATP 组的 SV 基本无变化,HR 增加9.9％(P>0.05);SNP 组血气分析的 BE 值负值增加;SNP 组和 ATP 组各有1例心电图 ST 段明显下降,停药复压后即恢复正常。结果表明:TNG 和 SNP 降压时前负荷降低,SV 下降 HR 增快,而 ATP 对 SV 和 HR 影响均不明显,似乎是个好的降压药物。     

三磷酸腺苷与硝普钠控制性降压对血流动力学影响的比较

在30例中青年病人中,分组比较了 ATP 与 SNP 降压对血流动力学的影响。在两组中 MAP和 SVR 降低非常显著(P<0.01)。HR 增快和 CVP 降低在 SNP 组非常显著,而 ATP 组则无明显变化(P>0.05)。停药后10min MAP 和 SVR 在 ATP 组很快回到降压前水平,而 SNP 组则高于降压前和对照组水平(P<0.05)。     

HLA-DRB1 Alleles are Associated With COPD in a Latin American Admixed Population

IntroductionWhile the molecular mechanisms of COPD pathogenesis remain obscure, there is mounting evidence supporting a key role for autoimmunity. Although human leukocyte antigens (HLA) alleles have been repeatedly associated with autoimmune processes, the relation between HLA and COPD remains largely unexplored, especially in Latin American (LA) populations. Consequently, this study aimed to investigate the presence of HLA class I and II alleles in COPD patients and healthy controls in a LA population with admixed ancestry.MethodsCOPD patients (n = 214) and age-matched controls (n = 193) were genotyped using the Illumina Infinium Global Screening Array. The classic HLA alleles were imputed using HLA Genotype Imputation with Attribute Bagging (HIBAG) and the Hispanic reference panel. Finally, the distribution of HLA-DRB1 alleles was reexamined in 510 randomly recruited unrelated volunteers.ResultsCODP patients showed a higher HLA-DRB1*01:02 allele frequency (6.54%) than healthy controls (3.27%, p = 0.04, OR = 2.07). HLA-DRB1*01:02 was also significantly associated with FEV₁ (p = 0.04) and oxygen saturation (p = 0.02), and the FEV₁/FVC ratio was higher in HLA-DRB1*15:01-positive patients (p = 9 × 10^?3).ConclusionWe report an association among HLA-DRB1 alleles, COPD risk and pulmonary function parameters for the first time in Latin Americans. Since HLA-DRB1 genetic variability relates to the individual autoimmune response, these results support a role of autoimmunity in the pathogenesis of COPD.     

桂西地区中老年人脂联素基因多态性与骨质疏松症的相关性

目的 探讨桂西地区中老年人脂联素基因多态性与骨质疏松症的相关性。方法 选取桂西地区中老年人志愿者623名,进行超声骨密度测量、脂联素基因多态性位点分析及SNPs位点的连锁不平衡分析。结果 同年龄（55岁以上）男性骨量值高于女性（P＜0.05）,骨量正常的个体比例随年龄的增长而下降,而骨质疏松症的患病率则随年龄增长而增加。脂联素基因5个SNPs位点均达到Hardy-Weinberg平衡（P＞0.05）,其中SNP位点rs1063539的CG基因型在骨质疏松病例组分布高于正常组,而GG基因型在病例组中的分布则低于正常组。CG型可能是骨密度的一个保护基因型,等位基因C可能与骨质疏松症的发生呈负相关。SNP位点rs3774261的AA基因型在病例组中的分布高于正常组。连锁不平衡检测发现,脂联素基因的5个SNP位点之间不存在连锁关系。结论 脂联素基因的SNP位点rs1063539和rs3774261与桂西地区中老年人群的骨质疏松有密切关系。     

硝普钢地冷冻复温人精子顶体反应的影响

本文目的是研究复温温度和硝普钠（SNP）对冷冻精子复温后成活率和顶体反应的影响和机制,结果表明：对冷冻精子37℃水浴复温效果优于41℃,高浓度SNP可减少精子成活率和顶体反应率,低浓度(0.2nmol/L)可促进精子成活率和顶体反应率,低浓度SNP可使Na^ -K^ -ATP酶活性增加,而对丙二醛（MDA）无影响。     

The amino acid mutations of the podocin in proteinuria: a meta-analysis

Abstract

While many previous studies have reported an association between the single-nucleotide polymorphisms (SNPs) of the podocin and proteinuria occurred, a conclusive relationship has not been defined in every oligoallelic state of amino acid (AA) mutations in podocin. In this study, we performed a meta-analysis of the published data to investigate the impact of the oligoallelic AA mutations of the podocin on proteinuria; a total 16 AA mutations were investigated for oligoallelic pathogenicity. Despite significant heterogeneity within some of the comparisons, the results revealed significantly higher risks of proteinuria in early-onset (onset age <16) individuals for five mutations (P118L, R138Q, R168H, V180M, and V260E), and in all onset ages individuals for five mutations (R138Q, G140X, R229Q, V260E, and V290M) compared to non-variant individuals. We also tested the steroid response in individuals with R229Q and E237Q. No statistically significant differences in the two mutations carrier rate were observed between steroid resistance patients and controls. No AA mutation was selected for meta-analysis on the recurrence of proteinuria after renal transplantation as lack of control data. In conclusion, our meta-analysis tested the pathogenicity of the oligoallelic AA mutations in podocin and suggested the potential causative mutations, and the alleles showing an association with protein susceptibility. The sensitivity and specificity of each causative mutation are pending further testing.