Genotype-Phenotype Correlation In Iranian Patients With Hb H Disease

Thalassemia is the most common genetic disorder in Iran. Some α-globin genotypes leading to Hb H disease may cause severe anemia and dependence on regular blood transfusions. In this study, 40 patients were analyzed for the molecular basis and the genotype-phenotype correlation of Hb H disease in Iran. α-Globin molecular analysis was performed by polymerase chain reaction (PCR) followed by agarose gel electrophoresis, reverse hybridization test strips or DNA sequencing. The most frequently observed α-globin genotypes were –α^3.7/– –^MED in 10 patients (25%), – –^20.5/α^–5ntα in six patients (15%) and – –^20.5/–α^3.7 in four patients (10%). A subset of the identified Hb H genotypes, including – –^MED/α^CSα, – –^MED/α^PolyA2α and α^CSα/α^CSα, was associated with a need for regular or irregular blood transfusions. Our findings provide a basis for predicting phenotype severity by identifying the Hb H genotype and making more selective decisions for prenatal diagnosis.     

HBeAg阳性慢性乙型肝炎患者HBV基因型和亚型与肿瘤坏死因子α的关系

目的探讨福建部分地区HBeAg阳性慢性乙型肝炎(CHB)患者HBV基因型、亚型的分布与血清肿瘤坏死因子α(TNF-α)水平及其基因启动子区-238、-308位点基因多态性的关系。方法选取福建部分地区203例HBeAg阳性CHB患者,采用HBV基因分型(B、C基因型)荧光定量PCR法检测HBV基因型或HBVS基因为直接测序法检测HBV基因型、亚型;聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)的方法检测TNF-α-238及-308位点基因多态性,酶联免疫吸附试验(ELISA)测定血清TNF-α水平,并对结果进行统计分析。结果 HBV基因型B、C分别占58.6%、41.4%,其中150例HBVS基因为直接测序,Ba亚型81例,Ce亚型69例;B基因型患者平均年龄和体重指数(BMI)小于C型(P=0.020)。HBV基因型B、C的TNF-α水平、TNF-α-238和-308位点基因多态性的分布无统计学差异(P0.05)。结论福建部分地区HBeAg阳性CHB患者HBV基因型以B型为主,其次是C型,仅见Ba和Ce亚型;B基因型患者较年轻,BMI小于C型;但HBV基因型B、C与TNF-α水平、TNF-α-238和-308位点基因多态性可能无关。     

OX40L基因变异与早发急性冠状动脉综合征风险关系的临床分析

目的 探讨OX40L基因变异与早发急性冠状动脉综合征风险之间的关系.方法 采用聚合酶链反应-序列特异性扩增(PCR-SSP)技术检测187例年龄≤55岁、早发急性冠状动脉综合征(ACS)患者和138例冠状动脉造影正常者m3850641位点M/G变异的基因型、等位基因及其分布频率;采用冠状动脉造影测量病变血管支数(DVN)和狭窄程度积分(SSI);应用ELISA法测试血浆sOX40L、血管细胞黏附分子(VCAM-1);应用散射比浊法测试血浆C反应蛋白(CRP)水平;分析OX40L基因变异与ACS风险、冠状动脉病变程度和血浆3个细胞因子之间的关系.结果 OX40L基因A/G变异与早发ACS风险显著关联,C等位基因比野生型早发ACS风险增高2.031倍(OR=2.03),变异型比野生型DVN、SSI、血浆OX40L、VCAM-1和CRP显著增高.结论 OX40L基因变异可能与早发ACS风险和冠状动脉病变程度有关:OX40L过度表达、细胞黏附和炎症反应可能是ACS发病的分子生物学基础.     

新疆伊犁地区食管鳞癌与儿茶酚-O-甲基转移酶基因Val158Met多态性的关联分析

目的 探讨儿茶酚-O-甲基转移酶(COMT)基因缬氨酸(Val)158甲硫氨酸(Met)(G→A转换)多态性在新疆伊犁地区人群中的分布及与食管鳞癌(ESCC)的关系.方法 采用以医院为基础的病例对照研究方法,研究对象共622名,包括214例ESCC患者,408名年龄、性别、民族相匹配的正常对照.以聚合酶链反应-限制性片段长度多态性方法分析COMT基因G/A多态性.结果 622名受试者COMT基因型频率分布依次为GG型占47.3%,GA型占42.3%,AA型占10.4%;等位基因G为68.4%,A为31.6%.食管癌组与正常对照组COMT基因型及等位基因频率分布差异无统计学意义(P＞0.05).分层分析显示,年龄≤60岁的食管癌组与正常对照组之间COMT基因型(x2=6.101)和等位基因频率(x2=4.493)差异有统计学意义(P值均＜0.05);哈萨克族、维吾尔族、汉族ESCC组间等位基因频率比较差异有统计学意义(x2=6.671,P＜0.05);三个民族正常对照组间COMT基因型(x2=13.567)及等位基因频率(x2=11.321)分布比较差异均有统计学意义(P值均＜0.05).将年龄及性别校正后,新疆伊犁地区食管癌组与正常对照组COMTVal158Met多态性在哈萨克族、维吾尔族、汉族之间差异均无统计学意义.结论 COMT基因Val158Met单核苷酸多态可能不是新疆伊犁地区食管鳞癌危险性的遗传标志.

Abstract：

Objective To explore the relationship between polymorphism of catechol-O-methyltransferase (COMT) gene valine (Val) 158 methionine (Met) (G to A transition)and the distribution in population and esophageal squamous cell carcinoma (ESCC) in Yili prefecture of Xinjiang.Methods A hospital based case-control study was adopted, a total of 622 subjects, which including 214 ESCC patients and 408 age, gender and ethnicity-matched normal control individuals.The polymorphism of COMT gene G to A transition was analyzed with PCR-restriction fragment length polymorphism approaches.Results The COMT genotype frequencies in 622 subjects in Yili prefecture were GG genotype accounted for 47.3%, GA type for 42.3% and AA type for 10.4%, G allele was 68.4% and A allele was 31.6%.There was no statistical difference in the COMT genotype and frequencies of allele distribution between ESCC group and control group.Furthermore, stratified analysis indicated that there was statistical difference between ESCC group and control group in subjects less than 60 years old.There was statistical difference in the allele distribution among Kazak,Uygur and Han ESCC groups.The COMT genotype and frequency of allele distribution among normal control groups of the three ethnic groups were statistically different.After corrected age and gender,there was no statistical difference in COMT Val158Met polymorphisms among Kazakh, Uygur and Han ethnic groups in both ESCC and control groups in Yili Prefecture of Xinjiang.Conclusion COMT gene Val158Met single nucleotide polymorphism may not be the genetic markers of ESCC risk in Yili Prefecture of Xinjiang.     

Hepatitis B virus: From diagnosis to treatment

During the next few decades, vaccination against hepatitis B virus (HBV) will dramatically change the epidemiological profile of this worldwide infection especially when Heath Policies encourage including HBV vaccination program for the newborns. However, it is still estimated that more than 2000 millions living people have met HBV. Symptomatic hepatitis with jaundice is less frequent than asymptomatic infection; however, as much as 350 millions of individuals remain chronically infected by HBV. In these cases, the need for efficient antiviral therapy remains clear when a viral replication is observed to control the risk of progression and the need for liver transplantation, which represents the only end-stage treatment. Indeed, patients having chronic hepatitis B (CHB) can now be successfully treated using nucleos(t)ide analogs (NA) or pegylated interferon (PEG-IFN). Therefore, beside vaccination, prevention of the progression of the disease to cirrhosis and liver decompensation, leading to end-stage liver disease and/or to hepatocellular carcinoma, by inhibiting viral replication seems to represent the best approach to improve survival. At last but not least, co-morbidities and other viral infections, leading also to chronic liver cirrhosis or liver inflammation such as the specific satellite delta virus (HDV), human immunodeficency virus (HIV) and/or hepatitis C (HCV) virus, are able to accelerate the progression and have to be taken in account. Interestingly, in treated infection, the dogma of the irreversibility of the liver fibrosis, when the cirrhosis is constituted, is tumbling down. In this review, we will focus on the clinical, virological and therapeutic aspects of hepatitis B infection in order to expose the proposals to follow-up and treat HBV-infected patients and the prevention of drug-resistant HBV mutants that frequently arise, leading to treatment failure and progression to liver disease.     

微卫星多态性和多位点序列分析技术在光滑念珠菌基因分型中的应用评估

目的评估微卫星多态性分析技术在临床光滑念珠菌基因分型中的作用。方法收集2011年1月至2012年12月仁济医院和东方医院临床分离的光滑念珠菌59株,采用多位点序列分析(MLST)和微卫星多态性分析技术进行基因分型,比较2种基因分型方法的结果和分辨力。结果 59株光滑念珠菌经MLST分型得到6个序列型,其中ST-7型43株、ST-10型7株、ST-15型和ST-55型各3株、ST-3型2株、ST-43型1株,鉴别力指数(DP)为0.456;经微卫星多态性分析方法分为10型,其中A型25株、B型10株、C型8株、D型6株、E型3株、F型和G型各2株、H~J型各1株,DP为0.770。结论微卫星多态性分析方法简便、快速,分辨力高于MLST技术,可作为实验室基因分型的首选方法。     

白介素18基因型及血清水平与2型糖尿病肾病的相关性

目的研究白介素18（IL-18）基因型及血清水平与2型糖尿病肾病（DN）的关系。方法采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术,检测360例2型糖尿病患者（160例伴DN）及180名正常对照组的IL-18的基因多态性,同时采用酶联免疫吸附试验（ELISA）检测血清IL-18水平。结果与对照组比较,糖尿病肾病组血清IL-18水平显著高于对照组（P〈0．01）。IL-18基因-137G／C多态性在两组人群中的分布差异有统计学意义（P〈0．05）,携带-137C等位基因的糖尿病肾病患者血清IL-18水平显著高于不携带者（P〈0．05）。结论IL-18基因-137G／C多态性与DN的发病可能具有相关性,其中C等位基因可能是DN发病的遗传易感基因;携带C等位基因的个体可能通过促进IL-18的高度表达进而增加了DN的发病风险。     

hMLH1．93G／A基因多态性与结直肠癌的相关性研究

hMLHl是DNA错配修复（MMR）系统的重要成员,在DNA复制过程中识别和修复错配碱基,其基因多态性对散发性结直肠癌（CRC）的诊断有重要价值。目的：探讨hMLHl启动子区-93G／A基因多态性与CRC的关系。方法：连续收集2008年1月-2010年10月的CRC患者312例,纳入同期正常对照300例。抽提所有人选者外周血白细胞DNA．以TaqManMGB探针荧光定量PCR检测hMLHl启动子区-93吲A基因多态性。结果：CRC组患者hMLHl-93G／A各基因型频率与正常对照组相比．差异无统计学意义（P=0．219）。对CRC组行分层分析示DukesCA期患者的A等位基因和AA基因型频率明显高于MB期患者（60．5％对48．1％,P=0．004;39．8％对23-3％,P=0．015）,淋巴结转移者的A等位基因和AA基因型频率亦明显高于无淋巴结转移者（60．5％对49．1％,P=0．010;39．5％对25．O％,P=0．031）。结论：hMLHl启动子区-93G／A基因多态性与CRC的发生无关,但A等位基因和AA基因型可能与CRC的进展有关。     

戊型肝炎病毒Ⅰ、Ⅱ与Ⅲ、Ⅳ基因型B细胞抗原表位的异同

目的：制备戊型肝炎病毒(HEV)缅甸株和墨西哥株ORF2重组蛋白(p166Bur和p166Mex)的单克隆抗体(McAbs)，用于分析HEV不同基因型B细胞抗原表位的特点。方法：将免疫BALB/C小鼠脾细胞与SP2/0骨髓瘤细胞融合，获得分泌抗-p166Bur和抗-p166Mex McAbs的杂交瘤细胞株，然后采用ELISA和免疫印迹法测定McAbs与不同基因型HEV ORF2编码蛋白p166的免疫反应性。结果：获得4株杂交瘤细胞株，即分泌抗-p166Bur McAbs的2G2、2B1以及分泌抗-p166Mex McAbs的D8G10和E5E12，其中2B1分泌的McAb仅能与第Ⅰ、Ⅱ基因型编码的重组蛋白结合，而其余3株分泌的McAbs既能与Ⅰ、Ⅱ基因型HEV的p166重组蛋白发生反应，也能与Ⅲ、Ⅳ基因型的p166蛋白反应。结论：HEV第Ⅰ、Ⅱ基因型与Ⅲ、Ⅳ基因型ORF2编码蛋白既有共同又有不同的B细胞抗原表位。     

云南省丙型肝炎病毒基因型及3b型遗传进化树分析

目的了解云南省丙型肝炎患者HCV基因型分布,对3b型进行遗传进化树分析。方法应用丙型肝炎非编码区ABC程序酶切分型法对云南省46例HCVRNA阳性血清标本进行HCV基因分型研究。从根据5′端非编码区(5′NCR)ABC分型结果判断为3b基因型10例标本中随机选择2例(A18、A32)进行HCV5′NCRcDNA双向测序。结果通过46例HCV5′NCRRNA阳性标本分型研究,云南省HCV感染基因型依次为1b型、3b型、3a、1a和2b型、2a/2b等混合型,各型所占比例分别为34.78%、21.74%、10.88%、6.52%、17.39%。2例(A18、A32)3b型进行HCV5′NCRcDNA双向测序,根据测序结果进行基因进化树分析,云南省HCV3b型与GenBank号中国HCV5′NCR3b株的同源性为99%~100%。结论云南省HCV主要流行基因型为1b型,其次为3b型;应用5′NCRABC分型法可得到准确分型结果。