术前血清IP-10、Mig和BLC水平与移植肾排异关系的研究

目的：研究术前血IP-10、Mig和BLC水平与移植肾排异的关系。方法：2005-08-2009-12行同种异体尸体肾移植（renal transplantation,RTx）手术、肾穿病理证实的急性排异（acute rejection,AR）及肾移植状态（RTx status,Ts）受者149例。总结两组受者术后6mo内AR的发生等流行病及临床资料,用ELISA法检测RTx受者术前血清IP-10、Mig和BLC水平。结果：AR组病人RTx术前IP-10和BLC血清水平明显高于Ts组（P=0.01;P=0.009）,年龄大的受者AR的风险较低（P=0.03）。术前IP-10血清水平大于3.57pg/mL者,与小于3.57 pg/mL者相比,AR发生率升高（59.74%vs 21.95%）。受者术前IP-10血清水平和年龄是RTx术后6mo内AR的独立危险因素（relative risk：1.565,0.893;95%CI：0.888-2.924,0.814-0.980;P=0.006,0.017）。结论：术前血IP-10水平是RTx术后AR的预测因素。     

VCAM1基因rs2392221单核苷酸多态性与肾移植术后急性排异发生的相关性

目的：阐述血管细胞黏附分子1(vascular cell adhesion molecule 1,VCAM1)基因rs2392221单核苷酸多态性（single nucleotide polymorphism,SNP）与肾移植后急性排异（acute rejection,AR）发生的相关性。方法：回顾性分析南京医科大学第一附属医院200例肾移植患者,根据肾移植术后是否发生急性排异分为急性排异（acute rejection,AR）组69例和非AR组131例。通过二代测序对VCAM1 rs2392221基因型进行检测。采用5个遗传模型分析VCAM1 rs2392221对AR的影响。结合临床和人口统计学数据,评估VCAM1 rs2392221基因多态性与肾移植术后急性排异的关联。结果：5个遗传模型研究显示VCAM1 rs2392221与肾移植术后急性排异显著相关,共显性模型CC vs. CT:OR=3.71,95%CI:1.82～7.58;CC vs. TT:OR=5.41,95%CI:1.14～25.75,P <0.001;显性模型OR=3.90,95%CI:1.97～7.72,P ...     

KIR及苴HLA配体与肾移植急性排斥反应的关系

目的 探讨供受者对杀伤细胞免疫球蛋白样受体(KIR)及其人类白细胞抗原(HLA)配体所介导信号传导通路在肾移植受者术后发生急性排斥反应(AR)中可能的作用.方法 回顾性分析53对肾移植供受者对HLA和KIR基因型,受者按照术后肾功能状态分为急性排斥组(n=19)和肾功能稳定组(n=34),探讨供者HLA、受者KIR基因型以及受者KIR/供者HLA配体组合型与肾移植急性排斥反应发生的相关性.结果 供者HLA、受者KIR基因表现型频率在急排组和稳定组的分布:供者HLA基因型HLA-CI/2、HLA-A3、HLA-A11、HLA-Bw4在两组间分布无显著统计学差异(P>0.05).受者KIR2DL2/2DS2在急排组表达低于稳定组(26.3% vs 55.9%,P=0.038),受者KIR基因组合型AA类型在急排组表达低于稳定组(31.6% vs 67.6%,P=0.011).供者HLA-Cw、受者KIR基因组合型术后急性排斥反应发生率:供者HLA-C1/C1类型低于非HLA-C1/C1类型(31.6% vs 46.7%,P>0.05).受者KIR基因组合型AA类型低于非AA类型(20.7% vs 52.2%.P=0.011).受者KIR/供者HLA配体组合型匹配情况:肾功能稳定组中KIR2DL2/HLA-C1和KIR2DL2/HLA-C1信号匹配率较急性排斥组高(P=0.030,P=0.028).结论特定的KIR/HLA配体组合型(如KIR2DL2/HLA-C1、KIR2DL2/HLA-C1)可以降低肾移植术后急性排斥反应的发生率.良好的供者HLA和受者KIR配型选择有利于同种异体肾移植的预后.     

KIR及其HLA配体与肾移植急性排斥反应的关系

目的探讨供受者对杀伤细胞免疫球蛋白样受体(KIR)及其人类白细胞抗原(HLA)配体所介导信号传导通路在肾移植受者术后发生急性排斥反应(AR)中可能的作用。方法回顾性分析53对肾移植供受者对HLA和KIR基因型,受者按照术后肾功能状态分为急性排斥组(n=19)和肾功能稳定组(n=34),探讨供者HLA、受者KIR基因型以及受者KIR/供者HLA配体组合型与肾移植急性排斥反应发生的相关性。结果供者HLA、受者KIR基因表现型频率在急排组和稳定组的分布:供者HLA基因型HLA-C1/2、HLA-A3、11、HLA-Bw4在两组间分布无显著统计学差异(P>0.05)。受者KIR2DL2/2DS2在急排组表达低于稳定组(26.3%vs55.9%,P=0.038),受者KIR基因组合型AA类型在急排组表达低于稳定组(31.6%vs67.6%,P=0.011)。供者HLA-C1/2、受者KIR基因组合型术后急性排斥反应发生率:供者HLA-C1/C1类型低于非HLA-C1/C1类型(31.6%vs46.7%,P>0.05)。受者KIR基因组合型AA类型低于非AA类型(20.7%vs54.2%,P=0.011)。受者KIR/供...     

肾移植受者并发巨细胞病毒感染的临床实验研究

目的 :探讨肾移植受者并发巨细胞病毒 (Cytomegalovirus ,CMV)感染后实验指标的变化及各指标的相关性 ,为诊断CMV感染及预防CMV病发作提供依据。方法 :运用Real TimePCR及流式细胞分析法等技术对肾移植受者的标本进行检测。结果 :(1)肾移植术后 14周内 ,尿液、血浆及白细胞中CMV DNA阳性检出率分别为 73 5 %、79 4 %及85 3% ;肾移植术后 18周内 ,尿液、血浆及白细胞中CMV DNA阳性检出率分别为 82 1%、85 7%及 85 7% ;(2 )肾移植术后 8周内 ,血浆及白细胞中CMV DNA的载量随术后时间的延长而增加 ;尿液中CMV DNA的载量在术后 12周内随时间的延长而波动性增加 ;(3)尿液、血浆及白细胞内CMV DNA检出率的峰值分别出现在肾移植术后第 12周、第 8周内及第 8周时 ;(4 )肾移植术后第 8周时 ,尿液中CMV DNA载量与CD3 T淋巴细胞 (P =0 0 0 2 0 )、CD4 T淋巴细胞 (P=0 0 0 19)、CD5 6 T淋巴细胞 (P =0 0 2 35 )及血清肌酐 (P =0 0 2 5 3)的相关性具有统计学意义 ,而与CD8 T淋巴细胞、丙氨酸转移酶、谷草转氨酶、血清尿素氮等的相关性无统计学意义 (P >0 0 5 ) ;血浆及白细胞中CMV DNA载量均只与丙氨酸转移酶的相关性有统计学意义 (P <0 0 0 1) ;结论 :(1)Real TimePCR是监测肾移植受者CMV感染进程的     

抑制型KIR基因组合型与肾移植急性排斥反应的关系

目的：探讨抑制型KIR基因组合型（AA类型）传导通路在尸体肾移植受者发生急性排斥反应（AR）中可能的作用.方法：应用PCR-SSP方法,检测24对肾移植供受者的KIR基因组合型,分析供受者AA类型和非抑制型KIR基因组合型（BB,AB类型）与肾移植术后AR的相关性.结果：24对供受者中AA类型供者9例,受者10例;BB类型供者3例,受者4例;AB类型供者12例,受者10例.AA类型受者AR发生率10%（1/10）,BB和AB类型受者AR发生率64%（9/14）（P〈0.05）.供者是AA类型受者AR发生率11%（1/9）,供者是BB和AB类型受者AR发生率60%（9/15）（P〈0.05）.供受者为AA/AA类型配型受者AR发生率为0%（0/4）,而供受者不是AA/AA类型配型受者AR发生率为50%（10/20）（P=0.114）.结论：AA类型受者肾移植术后AR的发生率低,对BB或AB类型受者选择AA类型的供肾能够降低AR的发生率.AA类型可能传导抑制信号为主.     

利用肾移植受者术后血清可溶性CD30预测早期急性排异反应

目的:评价利用肾移植受者术后血清可溶性CD30(sCD30)水平预测急性排异反应的可行性.方法:利用ELISA方法分别在术前、术后5 d和10 d检测231名肾移植受者的血清sCD30水平,根据肾移植受者术后1 mo内临床表现将他们分为三组:急性排异反应组(AR,n=49),肾功能延迟恢复组(DGF,n=11)和正常组(UC,n=171).结果:231名肾移植受者的血清sCD30水平由术前的(178±79)U/mL分别降至术后5 d的(52±30)U/mL和术后10 d的[(9±5)U/mL,P<0.001].AR组术后5 d的sCD30水平为(92±27)U/mL,高于uc组(41±20)U/mL和DGF组[(48±18)U/mL,P<0.001].而术前和术后10 d的sCD30水平在三组患者之间的差异无统计学意义.ROC曲线分析结果表明,利用术后5 d sCD30水平可以预测近期内即将出现的急性排异反应(曲线下面积0.95).并且,根据ROC曲线分析得出:将65 U/mL作为临界点可以较好的预测急性排异反应(特异性91.8%,敏感性87.1%).结论:检测肾移植受者术后5 d的血清sCD30水平可以预测移植后早期出现的排异反应.     

Shank3基因多态性与汉族儿童孤独症的病例对照研究

目的 探讨Shank3基因的单核苷酸多态性(SNPs)与汉族儿童孤独症的相关性.方法 采用Illumina CNV 370-Duo芯片和Illumina 610芯片对455例孤独症患者(孤独症组)和1 097例无孤独症及相关精神疾病儿童(对照组)的Shank3基因SNPs位点进行基因分型检测,对基因分型数据采用haploview4.1软件进行关联分析.结果 Shank3基因的rs736334、rs8137951位点的等位基因频率和rs9616816-rs736334的G-G、A-A及rs715586-rs8137951的G-A单体型频率在两组间的传递比较,差异有统计学意义(P＜0.05),但经1 000次模拟置换检验后的结果比较,差异无统计学意义(P＞0.05).结论 Shank3基因与汉族儿童孤独症的致病不存在相关性,Shank3基因可能不是汉族儿童孤独症的易感基因.     

ZNF804A基因外显子4区域单核苷酸多态性在中国汉族精神分裂症患者核心家系中的传递不平衡检验

目的 研究ZNF804A基因外显子4区域中的单核苷酸多态性位点(SNPs)和精神分裂症的相关性.方法 在69个中国汉族精神分裂症患者的核心家系中,采用MassARRAY等位基因分型技术对位于ZNF804A基因外显子4的7个SNPs以及2个侧翼的遗传标记进行基因分型和传递不平衡检验(TDT).结果 (1)存在4个罕见(少数等位基因频率＜1％)的SNPs(rs79776875、rs78816540、rs79082132和rs62198467),因其不符合分析要求,予以排除.(2)对其余5个SNPs( rs4667000、rs61739290、rs61739288、rs1366842、rs3731834)的分析表明,遗传标记rs3731834的传递不平衡结果具有统计学意义(P＜0.05).(3)在连锁不平衡分析中,对5个SNPs构建的单倍型分析显示其传递差异具有统计学意义(整体P＜0.05).结论 ZNF804A基因外显子4区域的SNPs与中国汉族人群精神分裂症的遗传易感性相关.     

NOS2基因单核苷酸多态性与单纯尘螨过敏性鼻炎相关性研究

目的 本研究探讨NOS2基因单核苷酸多态性（single nucleotide polymorphism,SNP）与单纯尘螨过敏性鼻炎（house dust mite-sensitive allergic rhinitis,HDM-sensitive AR）发生的相关性。方法 研究募集了HDM-sensitive AR患者385例和健康对照受试者424例。采集外周静脉血,提取基因组DNA。Sequenom iPLEX MassARRAY质谱法对NOS2基因上的6个标签SNPs（rs2297516,rs7406657,rs3794764,rs2872753,rs2779249,rs3794766）进行基因分型。结果 等位基因分析显示6个SNPs的等位基因频率在HDM-sensitive AR组与正常对照组间差异无统计学意义。基因型分析显示rs3794764的（AA+AG）基因型分布在HDM-sensitive AR患者组和正常对照组间差异存在统计学意义（P=0.047）,相对GG基因型是HDM-sensitive AR的危险因素（OR=1.413,95% CI：1.005~1.987）。多元线性回归分析显示在健康对照人群中rs3794766基因型与血清总IgE浓度具有显著相关性（P=0.019,β=-0.131,95% CI：-0.229~-0.021）。结论 NOS2基因可能是中国汉族人群HDM-sensitive AR的易感基因。     

Association of single-nucleotide polymorphisms of the tau gene with late-onset Parkinson disease.

CONTEXT: The human tau gene, which promotes assembly of neuronal microtubules, has been associated with several rare neurologic diseases that clinically include parkinsonian features. We recently observed linkage in idiopathic Parkinson disease (PD) to a region on chromosome 17q21 that contains the tau gene. These factors make tau a good candidate for investigation as a susceptibility gene for idiopathic PD, the most common form of the disease. OBJECTIVE: To investigate whether the tau gene is involved in idiopathic PD. DESIGN, SETTING, AND PARTICIPANTS: Among a sample of 1056 individuals from 235 families selected from 13 clinical centers in the United States and Australia and from a family ascertainment core center, we tested 5 single-nucleotide polymorphisms (SNPs) within the tau gene for association with PD, using family-based tests of association. Both affected (n = 426) and unaffected (n = 579) family members were included; 51 individuals had unclear PD status. Analyses were conducted to test individual SNPs and SNP haplotypes within the tau gene. MAIN OUTCOME MEASURE: Family-based tests of association, calculated using asymptotic distributions. RESULTS: Analysis of association between the SNPs and PD yielded significant evidence of association for 3 of the 5 SNPs tested: SNP 3, P =.03; SNP 9i, P =.04; and SNP 11, P =.04. The 2 other SNPs did not show evidence of significant association (SNP 9ii, P =.11, and SNP 9iii, P =.87). Strong evidence of association was found with haplotype analysis, with a positive association with one haplotype (P =.009) and a negative association with another haplotype (P =.007). Substantial linkage disequilibrium (P<.001) was detected between 4 of the 5 SNPs (SNPs 3, 9i, 9ii, and 11). CONCLUSIONS: This integrated approach of genetic linkage and positional association analyses implicates tau as a susceptibility gene for idiopathic PD.     

TAAR6基因多态性与精神分裂症关联性的Meta分析

目的:探讨人群中TAAR6基因多态性与精神分裂症的关联,阐明TAAR6基因与精神分裂症的关系。方法:通过计算机检索PubMed、Cochrance、中国知网(CNKI)和万方数据库,检索TAAR6基因多态性与精神分裂症关联的相关文献。检索时间为1994年1月—2013年5月公开发表的文献。根据纳入标准对相关文献进行筛查,选出合适的文献,提取文献中的数据。以比值比(OR)和95%可信区间(95%CI)为效应指标。采用RevMan 5.1软件对各项研究原始数据进行统计学分析,包括异质性检验、合并效应量以及评估发表偏倚。结果:按照纳入标准共有5篇文献符合条件,共选取了5个位点进行Meta分析,rs8192625位点的等位基因合并OR=0.93,95%CI=0.81~1.07,P=0.32;基因型合并OR=0.88,95%CI=0.76~1.02,P=0.08。rs4305745等位基因合并OR=0.96,95%CI=0.90~1.03,P=0.29;基因型合并OR=1.03,95%CI=0.92~1.14,P=0.62。rs6903874位点的等位基因合并OR=0.95,95%CI=0.86~1.04,P=0.27;基因型合并OR=0.93,95%CI=0.84~1.04,P=0.20。rs6937506位点的等位基因合并OR=0.95,95%CI=0.86~1.04,P=0.27;基因型合并OR=0.93,95%CI=0.83~1.03,P=0.17。rs7772821位点的等位基因合并OR=0.96,95%CI=0.87~1.05,P=0.35;基因型合并OR=0.96,95%CI=0.86~1.07,P=0.47。结论:人群中TAAR6基因5个位点的等位基因和基因型多态性与精神分裂症无关联,提示TAAR6基因多态性可能与精神分裂症无关联。     

Genome Wide Association Study:Searching for Genes Underlying Body Mass Index in the Chinese

Objective Obesity is becoming a worldwide health problem. The genome wide association(GWA) study particularly for body mass index(BMI) has not been successfully conducted in the Chinese. In order to identify novel genes for BMI variation in the Chinese, an initial GWA study and a follow up replication study were performed. Methods Affymetrix 500K SNPs were genotyped for initial GWA of 597 Northern Chinese. After quality control, 281 533 SNPs were included in the association analysis. Three SNPs were genotyped in a Southern Chinese replication sample containing 2 955 Chinese Han subjects. Association analyses were performed by Plink software. Results Eight SNPs were significantly associated with BMI variation after false discovery rate(FDR) correction(P=5.45×10-7-7.26×10-6, FDR q=0.033-0.048). Two adjacent SNPs(rs4432245 rs711906) in the eukaryotic translation initiation factor 2 alpha kinase 4(EIF2AK4) gene were significantly associated with BMI(P=6.38×10-6 4.39×10-6, FDR q=0.048). In the follow-up replication study, we confirmed the associations between BMI and rs4432245, rs711906 in the EIF2AKE gene(P=0.03 0.01, respectively). Conclusion Our study suggests novel mechanisms for BMI, where EIF2AK4 has exerted a profound effect on the synthesis and storage of triglycerides and may impact on overall energy homeostasis associated with obesity. The minor allele frequencies for the two SNPs in the EIF2AK4 gene have marked ethnic differences between Caucasians and the Chinese. The association of the EIF2AK4 gene with BMI is suggested to be ‘ethnic specific' in the Chinese.     

完全逆转的急性排斥对移植肾长期生存率的影响

目的　回顾性分析 946例肾移植患者急性排斥发生的时间、次数、治疗效果对移植肾长期存活的影响。方法　通过lifetable分别计算和比较无排斥组、一次排斥组、二次以上排斥组、早期排斥 (肾移植术后 90d内 )组、后期排斥 (术后 90d以后 )以及完全逆转组、部分逆转组患者肾生存率 ,并通过Cox回归分析相关危险因素。结果　急性排斥患者 ( 172例 )移植肾生存率要明显低于无急性排斥患者 ( 774例 ) ,5年和 10年生存率分别为 70 9%、2 9 8%和 93 3 %、83 3 % (P <0 0 0 0 1)。发生 2次以上急性排斥患者的肾长期生存率比无排斥和 1次排斥组要低得多 (P <0 0 0 0 1和P =0 0 0 3)。完全逆转组和部分逆转组患者的 5年、8年肾生存率分别为 93 9%、89 2和 6 3 1%、41 4% (P <0 0 0 0 1) ,前者和无排斥组患者肾生存率无明显差异 (P =0 96 )。排斥发生时间并不是影响移植肾生存的因素。结论　发生急性排斥反应的患者有较差的移植肾长期生存率 ,发生 1次且抗排斥治疗能完全逆转的患者其移植肾长期生存率与无排斥患者的肾生存率无明显差异。     

线粒体NDUFB6基因单核苷酸多态与2型糖尿病关系的研究

目的:通过对线粒体基因NDUFB6[NADH dehydrogenase (ubiquinone) 1 beta subcomplex]进行单核苷酸多态性(single nucleotide polymorphism, SNP)的检测,对高频率SNP进行基因分型,研究NDUFB6基因与2型糖尿病的相关性?方法:使用PCR+测序方法,以15个2型糖尿病患者和9个正常人为样本,对NDUFB6基因的启动子?外显子以及临近的内含子进行测序以确定该基因的SNP;对高频率的SNP,仍使用PCR+测序方法分别在192个2型糖尿病患者与正常人中进行基因分型?结果:总共发现NDUFB6基因的6个SNP,其中3个SNP出现频率较高?NDUFB6基因启动子的1个SNP(-1211C > T)在2型糖尿病人群与正常人群有显著差异(P < 0.05)?结论:NDUFB6基因启动子的-1211C > T多态性可能与2型糖尿病的发病有关?     

Polymorphisms in cytokine genes and their association with acute rejection and recurrence of hepatitis B in Chinese liver transplant recipients

BACKGROUND: Acute rejection (AR) and hepatitis B virus (HBV) recurrence after liver transplantation (LT) are the two major complications leading to chronic graft dysfunction. Genomic polymorphisms in interleukin (IL)-10, tumor necrosis factor (TNF)alpha and transforming growth factor (TGF)beta1 genes have been found to affect the susceptibility to certain diseases. However, the relationship between cytokine gene polymorphisms and risk of AR as well as HBV recurrence after LT in Han Chinese has not been reported. The objective of the present study was to investigate the association of polymorphisms within these cytokine genes with the risk of AR as well as HBV recurrence. METHODS: One hundred eighty six Chinese LT recipients in which 41 patients developed AR and 29 patients experienced HBV recurrence were enrolled; 151 age- and gender-matched healthy individuals were selected as controls. Single-nucleotide polymorphisms (SNPs) at loci of IL-10 -1082, -819, -592, and TNFalpha -308, -238, as well as TGFbeta1 -988, -800, -509, +869, and +915 were determined by using DNA sequencing and then confirmed by restriction fragment length polymorphism (PCR-RFLP). Analyses of linkage disequilibrium and haplotype frequency were performed using Haploview program. RESULTS: The -819 and -592 polymorphisms in the IL-10 gene were in complete linkage (r(2) = 1). Another linkage was found at -509 and +869 in the TGFbeta1 gene (r(2) = 0.66). A significant difference was observed in the distribution of allelic frequencies at position -819 and -592 in the IL-10 gene between ARs and non-ARs (p = 0.036, OR = 1.134, 95% CI 0.999-1.287 and p = 0.036, OR = 1.134, 95% CI 0.999-1.287, respectively). After adjustment for a Bonferroni correction, there was no significant difference between the polymorphism and AR (p >0.05). Furthermore, the overall genotype distribution between HBV recurrence patients and non-HBV recurrence patients was also not significantly different (p >0.05). CONCLUSIONS: Our study suggests that gene polymorphisms of IL10, TNFalpha, and TGFbeta1 do not have a major independent role in AR and HBV recurrence after LT and may not be risk factors of AR and HBV recurrence after LT in Chinese liver transplant recipients.     

Searching for a schizophrenia susceptibility gene in the 22q11 region

Objective To investigate a genetic association for schizophrenia within chromosome 22ql 1 in a Chinese Han population.Methods The PCR-based restriction fragment length polymorphism (PCR-RFLP) analysis was used to detect three singlen ucleotide polymorphisms (SNPs), rs165655 (A/G base change) and rs165815 (C/T base change) present in the ARVCF(armadillo repeat gene deletion in velocardiofacial syndrome) locus, and rs756656 (A/C base change) in the LOC128979(expressed sequence tags, EST) locus, among 100 Chinese family trios consisting of fathers, mothers and affected offspring with schizophrenia. Genotype data were analyzed by using linkage disequilibrium (LD) methods including haplotype relative risk (HRR) analysis, transmission disequilibrium test (TDT) and haplotype transmission analysis. Results The genotype frequency distributions of three SNPs were all in Hardy-Weinberg equilibrium (P＞0.05). Both the HRR and the TDT analysis showed that rs 165815 was associated with schizophrenia (22=6.447, df=- 1, P=0.011 and X^2=6.313, df=1, P=0.012, respectively),whereas the other two SNPs did not show any allelic association. The haplotype transmission analysis showed a biased transmission for the rs165655-rs165815 haplotype system (X2=17.224, df=3, P=0.0006) and for the rs756656-rs165655-rs165815 hapoltype system (X^2=20.965, df=7, P=0.0038). Conclusion Either the ARVCF gene itself or a nearby locus may confer susceptibility to schizophrenia in a Chinese Han population.     

利用二代测序数据探索SPRY基因家族与中国人群非综合征型唇腭裂的关联

目的 探索SPRY基因家族中的单核苷酸多态性及亲源效应与中国人群非综合征型唇腭裂发病风险的关联。方法 研究基于病例-双亲设计,以2016—2018年于北京大学口腔医院募集的 183个中国人群非综合征型唇裂合并或不合并腭裂(non-syndromic cleft lip with or without cleft palate,NSCL/P)核心家系(549人)为研究对象。利用其二代测序数据中的SPRY基因家族相关信息,展开单核苷酸多态性和亲源效应分析。该测序研究采用二阶段设计,第一阶段对24个家系进行全外显子组测序探索潜在阳性信号,第二阶段在159个家系的独立样本中对第一阶段结果进行验证。采用问卷调查收集NSCL/P患者及其父母的基本情况、患病情况、临床特征及孕期环境暴露等信息。收集患儿及其父母的血液并提取DNA进行基因检测以获取遗传信息。单核苷酸多态性分析采用传递不平衡检验,亲源效应分析采用Z检验,统计分析使用PLINK(v1.07)软件完成。第一阶段的多位点分析采用以家系为基础的序列核心关联检验方法,由R软件(v3.5.1)famSKAT-RC包完成。采用Bonferroni法对验证结果进行多重检验校正。结果 经过质量控制,第一阶段共有22个SPRY基因家族的位点纳入分析,结合位点的注释、功能预测结果及统计检验结果,纳入rs1298215244 (SPRY1)和rs504122 (SPRY2)两个位点进入二阶段验证。二阶段传递不平衡检验发现,rs1298215244: T>C、rs504122: G>C两种常见变异以及rs504122: G>T罕见变异与NSCL/P的关联达到Bonferroni多重检验校正后的显著性水平,位于SPRY1的rs1298215244: T>C其亲源效应矫正前具有统计学意义,但未能通过多重检验校正。结论 发现SPRY基因家族中的单核苷酸多态性与中国人群NSCL/P的发病风险存在关联,但未发现SPRY基因家族具有亲源效应。     

冠心病妇女绝经后雌激素替代治疗对趋化因子受体CXCR2的影响

目的：探讨经雌激素替代治疗后的绝经后冠心病妇女外周血单核细胞趋化因子受体CXCR2的变化。方法：选22例已绝经的冠心病妇女为观察组,20例绝经后健康妇女作为对照组,两组受试又随机分为干预组和安慰剂组,干预组口服结合型雌二醇（倍美力）,每日0．625mg,连续3个月,安慰剂组口服安慰剂（维生素C）,观察对象均分别于用药前及用药3个月末抽血测血清雌二醇（E2）水平,外周血单核细胞趋化因子受体CXCR2蛋白表达水平。结果：（1）治疗前冠心病组血清E2,CXCR2蛋白水平显低于正常对照组（P＜0．01）;（2）经过雌激素干预治疗3个月后,绝经后妇女血清E2水平均显上升（P＜0．01）,外周血单核细胞趋化因子受体CXCR2水平均显下降（P＜0．01）,且冠心病组较对照组变化更明显;（3）血清E2水平与CXCR2水平变化呈显负相关（r=-0.46).结论：雌激素替代治疗后的绝经后妇女外周血单核细胞趋化因子受体CXCR2下调,且有冠心病变化更明显,提示与雌激素的心脏保护作用有关。