上海地区I型自身免疫性肝炎与HLA-DRB1等位基因的相关性研究

目的 分析 HLA—DRB1等位基因与上海地区I型自身免疫性肝炎（AIH）的相关性,探讨 AIH的遗传易感背景。方法 采用序列特异性多聚酶链反应（PCR—SSP）,对32例I型AIH患者和48例健康对照者进行HLA—DRB1等位基因及有关基因亚型的分析。结果HLA—DR4基因频率在I型AIH患者中较健康对照组显著增高[46.9％与20.8％;相对危险度（RR）=3.35,x2=5.99,P=0.014]。其他等位基因在两组间差异无显著性。进一步对HLA-DR4等位基因亚型的分析表明,I型AIH患者组DRB1＊0405的基因频率较健康对照组有增加趋势（21.9％与6.3％,x2=4.23,P=0.04,但 Pc=0.08）。HLA—DRβ分子的第3等位基因高变区第71位精氨酸残基的频率在I型AIH患者中显著增高（46.9％与 18.8％,x2=7.14,P=0.008）。结论 上海地区I型 AIH的发病与HLA—DR4以及HLA—DRB1第3高变区DR71位精氨酸残基相关。     

Genetic alterations of hepatocellular carcinoma by random amplified polymorphic DNA analysis and cloning sequencing of tumor differential DNA fragment

AIM: To study the genetic alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC), and to find the tumor related DNA fragments. METHODS: DNA isolated from tumors and corresponding noncancerous liver tissues of 56 HCC patients was amplified by random amplified polymorphic DNA (RAPD) with 10 random 10-mer arbitrary primers. The RAPD bands showing obvious differences in tumor tissue DNA corresponding to that of normal tissue were separated, purified, cloned and sequenced. DNA sequences were analyzed and compared with GenBank data. RESULTS: A total of 56 cases of HCC were demonstrated to have genetic alterations, which were detected by at least one primer. The detestability of genetic alterations ranged from 20% to 70% in each case, and 17.9% to 50% in each primer. Serum HBV infection, tumor size, histological grade, tumor capsule, as well as tumor intrahepatic metastasis, might be correlated with genetic alterations on certain primers. A band with a higher intensity of 480 bp or so amplified fragments in tumor DNA relative to normal DNA could be seen in 27 of 56 tumor samples using primer 4. Sequence analysis of these fragments showed 91% homology with Homo sapiens double homeobox protein DUX10 gene. CONCLUSION: Genetic alterations are a frequent event in HCC, and tumor related DNA fragments have been found in this study, which may be associated with hepatocarcin-ogenesis. RAPD is an effective method for the identification and analysis of genetic alterations in HCC, and may provide new information for further evaluating the molecular mechanism of hepatocarcinogenesis.     

Genetic variations in the SMAD4 gene and gastric cancer susceptibility

AIM:To explore the association between mothers against decapentaplegic homolog 4 (SMAD4) gene polymorphisms and gastric cancer risk.METHODS:Five tagging single nucleotide polymor-phisms (tSNPs) in the SMAD4 gene were selected and genotyped in 322 gastric cancer cases and 351 cancerfree controls in a Chinese population by using the polymerase chain reactionrestriction fragment length polymorphism method.Immunohistochemistry was used to examine SMAD4 protein expression in 10 normal gastric tissues adjacent to...     

先天性心脏病遗传学研究现状及挑战

先天性心脏病（先心病）是一类重要的有临床意义的出生缺陷,保守估计其发生率为50/1000活产儿。该病的遗传学机制相当复杂：染色体畸变,单基因突变和多基因突变都有可能导致先天性心脏畸形。本综述回顾了近年来该领域研究的现状及面临的挑战,并提出未来可能的研究方向。     

Black and White adults' perspectives on the genetics of nicotine addiction susceptibility

Aims

Emerging research may soon lead to improved quit rates via genetically-tailored smoking cessation treatment. The purpose of this study was to explore individuals' beliefs and attitudes about genetic testing in this context, and how these may differ across racial groups.

Design

Two site qualitative study.

Methods

Eleven focus groups were conducted in 2007 with 51 Black and 55 White adult participants in Montgomery, AL and Baltimore, MD.

Measurements

Questions were asked about smoking as an addiction, the role of genetics in nicotine addiction susceptibility, and undergoing genetic testing to receive tailored smoking cessation treatment. Data were analyzed using content analysis.

Findings

Most participants believed that smoking was an addiction yet were unwilling to endorse the notion that genetics played a role in nicotine addiction susceptibility. However, 91% of White participants and 62% of Black participants indicated that they would likely take a genetic test that would match them to their optimal smoking cessation treatment. The primary potential benefit was a vague sense that additional knowledge about oneself would be of value. Primary barriers included disinterest and skepticism about the test, unwillingness to believe that genetics played a role in nicotine addiction or treatment response, and concerns about psychological consequences.

Conclusions

The majority of participants, particularly Black participants, did not believe that genetics played a significant role in nicotine addiction susceptibility but were willing to undergo genetic testing. Participants identified some benefit to tailoring smoking treatment by genotype. However, participants also expressed skepticism about the test and concerns about its consequences; these issues would need to be addressed in the clinical encounter.     

Epistatic interaction of CREB1 and KCNJ6 on rumination and negative emotionality

G protein-activated K+ channel 2 (GIRK2) and cAMP-response element binding protein (CREB1) are involved in synaptic plasticity and their genes have been implicated depression and memory processing. Excessive rumination is a core cognitive feature of depression which is also present in remission. High scores on the Ruminative Response Scale (RRS) questionnaire are predictive of relapse and recurrence. Since rumination involves memory, we tested the hypothesis that variation in the genes encoding GIRK2 (KCNJ6) and CREB1 mechanisms would influence RRS scores. GIRK2 and CREB1 polymorphisms were studied in two independent samples (n = 651 and n = 1174) from the general population. Strongly significant interaction between the TT genotype of rs2070995 (located in KCNJ6) and the GG genotype of rs2253206 (located in CREB1) on RRS were found in both samples. These results were validated in an independent third sample (n = 565; individuals with personality disorders) showing significant main effect of the variants mentioned as well as significant interaction on a categorical diagnosis of Cluster C personality disorder (obsessional-compulsive, avoidant and dependent) in which rumination is a prominent feature. Our results suggest that genetic epistasis in post-receptor signaling pathways in memory systems may have relevance for depression and its treatment.     

5个家族性腺瘤样息肉病家系APC基因突变研究

目的探讨结肠腺瘤病（adenomatous polyposis coli,APC）基因在5个云南省家族性腺瘤样息肉病（Familial adenomatous polyposis,FAP）家系的突变情况。方法对昆明医科大学第一附属医院住院病例进行统计,查找FAP家系,绘制家系图谱。抽取该家系成员外周静脉血提取DNA,利用PCR方法扩增APC基因,应用DNA自动测序仪进行测序。结果 5个家系（2个白族家系,2个彝族家系,1个汉族家系）中,只有汉族家系查出APC基因1196S〉SX（1196号氨基酸由丝氨酸变为了终止密码子）的突变。其余家系均未查出APC基因的无义突变。结论通过对5个FAP家系进行APC基因测序,发现云南省少数民族家系APC基因的突变率不高,APC基因突变存在民族差异。     

CD38基因多态性与白血病生物学特征的相关性分析

目的本研究旨在通过检测中国西北人群白血病患者和健康对照组中CD38基因184位点的基因型分布特点,探讨CD38基因多态性与中国西北人群白血病易感的相关性,揭示白血病患者CD38基因多态性与白血病不同生物学特征的相关性以及对其预后的影响。方法采用病例对照设计,包含100例患者,100例正常对照,采用聚舍酶链反应一限制性片段长度多态性技术（PCR-RFLP）检测cD38基因184住点的多态性,应用x2检验和精确概率法比较各基因型频率在病例组与对照组之间的差异。结果白血病组与对照组相比,GG、GC、CC基因型频率无统计学差异（P=0．072）。初诊时WBC〉50×109／L、Hb〈100g／L、LDH〉450、脾脏肿大、伴有Ph染色体异常的患者与对照组GG、GC、CC基因型比较差异有统计学意义（P〈O．05）。结论CD38基因184位点多态性可能与白血病的发病风险无关,GG、GC变异基因型可能与白血病患者主要生物学特征有关。