Distribution of patients with Wilson disease carrying the H1069Q mutation in Austria

BACKGROUND/AIMS: More than 100 different mutations of the Wilson disease (WD) gene have been reported so far, but only the H1069Q mutation is frequently found in patients of North and East European origin. We wanted to know if there is a connection between the migration pattern in Central Europe and the geographical distribution of this mutation in Austria. METHODS: One hundred and nine patients (91 index patients and 18 asymptomatic siblings) with WD diagnosed in Austria were included in this study. Eighty-one of the 91 index patients were born in Austria. Evaluation criteria included the place of birth of each member of the study group, as well as of his parents and grandparents. RESULTS: Out of the 81 index patients born in Austria, 72 were tested for the H1069Q mutation. Twelve (16.7%) were homozygous carriers of the H1069Q mutation, 29 (40.3%) were compound heterozygous and 31 (43.0%) had an unknown mutation on both chromosomes. Eight of the twelve H1069Q homozygotes were born close to the northeastern border of Austria (neighboring the Czech Republic, Slovakia and Hungary). Compound heterozygous patients showed a more variable geographical distribution with respect to their birthplace. The patients with unknown mutation were scattered all over Austria. CONCLUSION: These data provide further evidence that the H1069Q mutation originates from Eastern Europe. In patients from these countries the PCR-based testing for this mutation may be useful for differential diagnosis and family studies.     

胱硫醚β合成酶基因多态性与脑卒中相关性的研究

目的　研究胱硫醚β合成酶 (CBS)基因 T2 7796 C多态性与脑卒中的遗传相关性。方法　采用限制性内切酶片段长度多态性方法 (PCR RFL P) ,对 5 9例脑卒中患者和 6 5例健康人 CBS基因 T2 7796 C多态性位点进行检测。结果　病例组 C等位基因占 5 6 .8% ,T等位基因占 4 3.2 % ;正常对照组 C等位基因占 5 1.5 % ,T等位基因占 4 8.5 % ;CBS基因 T2 7796 C多态性位点与脑卒中无明显相关 (P>0 .0 5 )。脑卒中组与正常对照组之间 3种等位基因型分布频率亦均无明显差异 ,其中 CC为 35 .6 %比 2 4 .6 % ;CT为 4 2 .4 %比 5 3.8% ;TT为2 2 .0 %比 2 1.5 % ;P>0 .0 5。缺血性卒中和出血性卒中组间 C、T等位基因及 3种等位基因型分布频率也均无显著性差异 (P均 >0 .0 5 )。结论　 CBS基因 T2 7796 C多态性位点与脑卒中无明显相关 ;T2 7796 C多态性位点与脑卒中的类型 (缺血性或出血性 )也无明显相关。     

拉米夫定耐药患者乙型肝炎病毒P区变异及其特点

【目的】观察使用拉米夫定抗病毒治疗患者乙肝病毒（HBV）P区变异及特点,为临床拉米夫定耐药的预防提供依据。【方法】对52例服用拉米夫定患者进行研究,对其HBV聚合酶逆转录酶区基因进行分析。采用荧光定量PCR试剂进行HBV基因分型。通过巢式PCR引物扩增P区,扩增产物经纯化后进行测序分析。【结果】在52例拉米夫定耐药患者中,其平均年龄（33．6±13．4）岁,共有30例发现了HBVP区耐药位点变异,检出率为57．3％。M204I为主要的突变类型。其中发现P区变异的在病毒学反弹的、治疗中应答不佳的及停药后复发的患者中分别19例,6例,5例,三者变异发生率分别为82．6％,42．9％,33．3％,其变异发生率有显著差异（P〈0．05）。疗程在1年,2年及2年以上的,P区突变检出率分别为26．3％,72．7％,81．8％,三组之间比较有显著差异。P区突变组用药时间明显长于无P区突变组,分别为（27．7±19．9）个月,（13．9±7．6）个月（P〈0．005）。【结论】拉米夫定治疗后耐药患者HBVP区变异发生率也随着时间的延长而增高。且有P区变异的平均用药时间明显长于未检测到P区变异组,故在拉米夫定长期治疗过程中,应定期观察其耐药的产生,及时调整治疗方案,以维持临床疗效的稳定性。     

C677T mutation in methylentetrahydrofolatereductase gene in patients with venous thromboses from the central region of Russia correlates with a high risk of pulmonary artery thromboembolism

AIM: To investigate genetic factors of risk (RF) to develop venous thrombosis and pulmonary artery thromboembolism (PATE) in population of central Russia. MATERIAL AND METHODS: We studied polymorphism of the genes of coagulation factor II (G20210A), factor V (G1691A) and methylentetrahydrofolatereductase (MTHFR) with polymerase chain reaction and restriction analysis of DNA amplified sites. We estimated prevalence of the mutations in healthy population and in patients with flebothrombosis as well as effects of the mutations on a PATE rate in patients with thrombosis. We examined 97 patients with documented flebothrombosis. PATE was detected in 54 of them. The control group consisted of 56 healthy volunteers matched by age and gender. RESULTS: G1691A mutation in the gene of coagulation factor V (Leiden mutation of factor V--LMFV) in healthy population occurred in 3.6%, in patients with flebothromboses--in 19.6% (OR = 6.58; 95% CI from 1.47 to 29.42; p = 0.006). Heterozygous mutation G20210A in prothrombine gene was detected in 8 (8.2%) patients (p = 0.027), while this mutation was registered in none controls. Polymorphism of MTHFR gene (C677T) was seen both in the control and patients (60.7 and 52.6%, respectively). LMFV occurrence in patients with flebothrombosis and PATE is less than in patients with flebothrombosis without TEPA (16.7 and 23%, respectively). The PATE risk is significantly higher in carriers of mutant allele 677CT and 677TT of MTHFR compared to patients free of this mutation (OR = 3.11; CI 95% from 1.35 to 7.15; p = 0.006). Homozygous inheritance of this mutation in males combined with PATE in 100% cases. Of 8 carriers of heterozygous mutation G20210A in prothrombin gene PATE was detected in 5 carriers. CONCLUSION: LMFV and mutation G20210A in prothrombin gene are genetic risk factors of venous thrombosis. LMFV is not a PATE risk factor. Mutation C677T in MTHFR gene has no influence on the risk of venous thromboses but makes PATE much more probable. This suggests that it may be a genetic risk factor of PATE in this disease.     

采用荧光定量PCR检测JAK2基因V617F突变

目的 建立荧光定量PCR检测JAK2基因V617F突变的方法,评估JAK2 V617F突变在诊断骨髓增殖性疾病和白血病中的临床意义.方法 选取71例慢性粒细胞性白血病(CML)、22例原发性血小板增多症(ET)、11例原发性骨髓纤维化(PMF)、9例真性红细胞增多症(PV)、7例嗜酸粒细胞增多症患者,分别采用荧光定量PCR、突变特异性扩增系统(ARMS)对JAK2 V617F突变进行检测,并采用基因测序对结果进行验证.将具有JAK2 V617F纯合子突变的人类红白血病细胞株(HEL)DNA作为阳性对照,比较荧光定量PCR和ARMS对JAK2基因V617F突变的检测敏感度.结果 采用荧光定量PCR检测,野生型的熔解温度(Tm)峰出现于(75.0±0.2)℃处,突变型的Tm峰出现于(76.6±0.2)℃处.JAK2基因V617F突变在PV、ET、PMF等骨髓增殖性疾病中的检出率分别为8例(88.9%)、12例(54.5%)、7例(63.6%),但在71例CML中只检出1例(1.4%).荧光定量PCR与ARMS的结果符合率为100%,结果经过测序证实.使用荧光定量PER法可在每106个正常自细胞中检出低至102个HEL细胞,而使用ARMS方法时要在每106个正常白细胞中HEL细胞达到104个时,方可检测出,前者比后者方法灵敏100倍.结论 成功地建立了荧光定量PCR检测JAK2基因V617F突变的方法,比ARMS更灵敏、简便,适合临床使用.JAK2基因V617F突变在骨髓增殖性疾病中有较高的检出率,可作为骨髓增殖性疾病特异性诊断指标.     

Is the common 677C-->T mutation in the methylenetetrahydrofolate reductase gene a risk factor for neural tube defects? A meta-analysis

The common 677C-->T mutation (+) in the 5,10-methylenetetrahydrofolate reductase gene, resulting in decreased activity of the enzyme, has been associated with spina bifida neural tube defects (NTD). We combined all known Dutch control groups, a total of 1273 individuals, and found a prevalence of the 677C-->T mutation of 8.4%. When compared with the frequencies in 55 SB patients and to mothers with a child with SB their parents, this gave an OR of 1.9 [95% CI 1.1-3.3] for mothers and an OR of 1.5 [95% CI 0.74-3.1] for patients. The frequency of this mutation and its associated risk for NTD may be population-dependent. However, the frequencies of the 677C-->T mutation in different national and international control groups are almost all in the same range. We therefore combined the observed frequencies of the 677C-->T mutation in all reported studies. The mutation was present in 9.2% of controls, resulting in ORs for all reported NTD patients and their parents of: 1.7 [95% CI: 1.1-2.6]; 1.8 [95% CI: 1.1-3.1] and 1.9 [95% CI: 1.3-2.8] for mothers (combined prevalence 14.5%), fathers (combined prevalence 15.5%) and NTD patients (combined prevalence 16.4%), respectively, vs. all international controls. This meta-analysis confirms that the 677C-- >T mutation is a genetic risk factor for NTD.      

Frequency of Factor V Leiden in Juvenile Migraine With Aura

Patients with migraine are known to be at risk for stroke. It has been reported that in a group of patients with cerebral ischemia and the Leiden mutation of factor V, 67% had classical migraine. We have studied the frequency of this mutation in a group of Italian children and adolescents affected by migraine with aura.
The Leiden mutation was detected in 2 (3.5%) of 57 patients and in 8 (3.7%) of 219 controls. The 2 patients carrying the mutation had no peculiar characteristics as compared with the rest of the migrainous population. In our study, the frequency of the Leiden mutation in patients was not different from that of controls. These data contrast with those collected in the Finnish population and in a group of northwestern Italian adult patients, but agree with results previously reported from The Netherlands.     

Frequency of factor V Leiden in juvenile migraine with aura

Patients with migraine are known to be at risk for stroke. It has been reported that in a group of patients with cerebral ischemia and the Leiden mutation of factor V, 67% had classical migraine. We have studied the frequency of this mutation in a group of Italian children and adolescents affected by migraine with aura. The Leiden mutation was detected in 2 (3.5%) of 57 patients and in 8 (3.7%) of 219 controls. The 2 patients carrying the mutation had no peculiar characteristics as compared with the rest of the migrainous population. In our study, the frequency of the Leiden mutation in patients was not different from that of controls. These data contrast with those collected in the Finnish population and in a group of northwestern Italian adult patients, but agree with results previously reported from The Netherlands.     

某地区结直肠癌患者KRAS基因及BRAF基因突变状态的检测分析

目的 检测某地区结直肠癌患者KRAS基因和BRAF基因的突变状态及其与年龄、性别的关系.方法 由某地区30例结直肠癌患者石蜡组织中提取DNA,通过直接测序法及荧光定量PCR法检测KRAS基因及BRAF基因突变状态.结果 KRAS基因突变率为43.3%,共发现6种突变类型,主要位于12、13密码子,其中以c.38G>A突变率最高(38.5%).单因素及多因素分析均提示KRAS突变与年龄或性别无相关性.BRAF基因突变率为0.结论 某地区结直肠癌患者KRAS基因突变率高,靶向治疗前进行突变状态检测具有重要临床价值.     

Mutation in the Hepatitis E Virus Polymerase and Outcome of Ribavirin Therapy

Hepatitis E virus (HEV) can lead to chronic infection in solid-organ transplant patients. Ribavirin is efficient for treatment of chronically infected patients. Recently, the1634R mutation in the HEV polymerase has been associated with treatment failure. However, it is unclear if this mutation can be used as a prognostic marker of treatment outcome. We studied the prevalence of the 1634R mutation in the HEV polymerase of patients starting ribavirin therapy, the influence of the 1634R variants on the viral response, the frequency of the 1634R mutation in patients whose treatment failed, and its impact on ribavirin retreatment. We analyzed pretreatment samples from 63 solid-organ transplant patients with chronic hepatitis E using deep sequencing; 42 patients had a sustained virologic response (SVR), and 21 were non-SVR patients. We detected the 1634R variant by deep sequencing in 36.5% (23/63) of the patients (proportions, 1.3 to 100%). The 1634R variant was detected in 31.0% (13/42) of baseline plasma samples from patients with SVR and in 47.6% (10/21) in the other patients (P = 0.2). The presence of this mutation did not influence the initial decrease in viral RNA. Lastly, a second prolonged ribavirin treatment led to SVR in 70% of the patients who initially did not have SVR, despite the presence of the 1634R variant. We conclude that the presence of the 1634R variant at ribavirin initiation does not lead to absolute ribavirin resistance. Although its proportion increased in patients whose treatment failed, the presence of the 1634R variant did not compromise the response to a second ribavirin treatment.     

98例原发性血小板增多症Jak2基因突变的定量分析及其临床意义

为研究JAK2V617F在原发性血小板增多症（ET）患者中的发生率和突变类型,定量分析突变转录本水平并初步探讨其临床意义,采用ARMS（amplification—refractorymutationsequencing）PCR法检测JAK2V617F突变的发生率及其突变类型,采用毛细管电泳法定量分析JAK2V617F突变转录本水平。结果显示：98例ET患者中59例JAK2V617F为阳性,其中纯合突变18例。纯合突变及杂合突变患者的平均年龄均较野生型为高（P值均〈0．05）;18例纯合突变患者的白细胞计数高于41例杂合突变者,且二者均高于野生型（P值均〈0．05）。毛细管电泳定量分析显示,纯合突变患者JAK2V617F突变转录本水平为（89．9±6．7）％,高于杂合突变患者的（57．1±6．7）％（P〈0．05）;年龄小于60岁患者的JAK2V617F突变转录本水平为（62．3±16．5）％,低于年龄大于60岁患者的JAK2V617F突变转录本水平为（72．4±15．8）％（P〈0．05）。JAK2V617F阳性组中血栓的发生率高于阴性组,其中纯合突变者高于杂合突变者,发生血栓者的JAK2V617FF转录本水平高于无血栓者（P值均〈0．05）。结论：JAK2V617F阳性与阴性ET患者有着不同的临床特征,分析其突变类型及检测其转录本水平对明确疾病状态、观察疾病进展及指导治疗有重要意义。     

成人T细胞急性淋巴细胞白血病中NOTCH1突变的特征研究

本研究旨在阐明NOTCH1突变在成人T细胞急性淋巴细胞白血病（T-ALL）中的特征及临床意义。通过对42例成人T-ALL患者外显子（exon）26／异二聚体N末端（HD-N）、exon27／异二聚体c末端（HD-C）、exon28和exon34／脯氨酸-谷氨酸-丝氨酸-苏氨酸（PEST）区域进行扩增、克隆和测序,研究NOTCH1突变的发生率、突变位点和类型、突变与临床和实验室指标的相关性及其预后意义。结果显示,本组成人T-ALL中NOTCH1突变率66．7％（28／42）,共发现45种NOTCH1突变,最多见于HD-N（48．9％,22／45）和PEST（40．0％,18／45）;HD-N结构域突变最多位于氨基酸位点1575（L1575P）（25．O％,7／28）,PEST结构域突变最多位于氨基酸位点2443（14．3％,4／28）;初诊时白细胞计数大于10×10^9／L者NOTCH1突变组显著高于无突变组（91．7％vs 54．5％,P=0．021）;骨髓原始及幼稚淋巴细胞比例超过50％者突变组显著高于无突变组（95．8％vs 57．1％,P=0．006）;流式免疫表型CDl0阳性表达率突变组显著高于无突变组（51．9％vs0％,P=0．006））,CD15和CD11b阳性表达率突变组显著低于无突变组（分别为5．3％vs 42．9％,P=0．047和0％vs57．1％,P=0．002）。结论：成人T-ALL的NOTCH1突变具有不同于儿童的突变特征和预后意义,而且中国成人T-ALL的NOCH1突变与西方国家相比可能存在差异。     

四引物扩增受阻突变体系快速检测Wilson病基因Arg778 Leu突变

目的 建立一种不需要限制性片段长度多态性或直接测序的新方法检测肝豆状核变性（WD）病人突变热点ATP7B基因的Arg778Leu突变基因型。方法 用四引物扩增受阻突变体系聚合酶链反应（tetra-primer amplification refractory mutation system-PCR,tetra-primer ARMS—PCR）检测47例WD患者和30例正常对照的ATP7B基因Arg778Leu突变,并用测序进行验证。结果 47例WD患者中检出Arg778Leu纯合突变4例,杂合突变14例,总检出率38．3％（18／47）;30例正常对照未发现突变;DNA测序结果与四引物ARMS—PCR结果完全一致。结论 ATP7B基因Arg778Leu突变是中国人WD突变热点;四引物ARMS—PCR法检测Arg778Leu突变有快速、简便、准确的优点,可以区分等位基因是否纯合,适于大样本的人群筛查。此法也可用于检测其他点突变。     

胸水细胞p53和K-ras基因突变对于肺癌的诊断价值

目的：研究p53和K-ras基因在良恶性胸水细胞中的突变情况。方法 研究组为34例伴有恶性胸水的肺癌患者，对照组为28例出现胸水的结核性胸膜炎和其他炎性胸膜炎患者。常规抽水胸水，提取胸水细胞DNA，采用PCR-SSCP方法，分别对p53基因第7、8外显子和K-raS基因第1、2外显子进行突变分析。结果 研究组p53基因突变率为41．2％，而对照组只有7．1％，明显低于肺癌患者（P〈0．05）；研究组K-ras基因突变率（32．4％）也明显高于对照组（3．6％）（P〈0．05）。联合应用p53和K-ras基因突变检测可将胸水细胞中肺癌阳性检出率提高至61．8％。结论 p53和K-ras基因突变是良恶性胸水鉴别诊断的潜在生物学指标。     

原发性骨弥漫性大B细胞淋巴瘤的临床病理特征、突变图谱及预后影响因素分析

目的 探讨原发性骨弥漫性大B细胞淋巴瘤（primary bone diffuse large B-cell lymphoma, PB-DLBCL）的临床病理特征、突变图谱及预后影响因素。方法 纳入2006年5月至2021年9月上海交通大学医学院附属瑞金医院收治的初治PB-DLBCL患者37例。采用淋巴瘤相关55个基因靶向测序描绘PB-DLBCL患者的突变图谱，采用单因素Cox回归模型评估临床因素和基因突变与无进展生存期（PFS）和总生存期（OS）之间的关系。结果 37例初治PB-DLBCL患者中，男性21例（56.8%），年龄>60岁21例（56.8%）,Ann Arbor分期为Ⅳ期22例（59.5%），非生发中心来源（non-GCB）亚型22例（59.5%），国际预后指数评分为3～5的患者18例（48.6%）。靶向测序结果显示，MYD88、PIM1、CCND3、CD79B、CIITA、HIST1H1E、KMT2C、PRDM1、TNFAIP3、ZFP36L1为常见突变，突变频率高于20%。单因素分析结果显示，BTG2基因突变（P=0.015）、MYD88基因突变（P=0.049）...     

p53基因突变在肺癌早期诊断中的应用

目的 探讨p53基因突变在肺癌早期诊断中的应用价值。方法 应用聚合酶链式反应——单链构象多肽性分析(PCR—SSCP)方法，对107例疑诊肺癌患者的纤支镜标本进行p53基因分析，分析结果与病理对照或随访以证实阳性的可信度。结果 43例病理诊断肺癌的患者中，25例p53基因发生突变，占58．2％。在64例疑诊肺癌但病理学阴性的患者中发生p53基因突变18例，无p53基因突变的46例，经过28个月的随访，p53基因突变组有8例诊断为肺癌，占44．4％，而无p53基因突变组仅有2例诊断为肺癌，占4．7％，两组之间差异显著。结论 通过对患者纤支镜标本p53基因分析，能对高危人群及个体危险度进行较准确的估计，有助于肺癌的早期诊断。     

Automated detection of the G20210A prothrombin mutation using the LCx microparticle enzyme immunoassay.

BACKGROUND: The prothrombin mutation, a G/A transition at position 20210 in the 3' untranslated region of the prothrombin gene, is associated with an increased risk of deep venous thrombosis and obstetrical complications. Several methods have been developed to detect the mutation; however, given the increased demand for this test in risk factor assessment, the development of simple and efficient screening methods has become necessary. METHODS: We have used a rapid, sensitive, and precise method developed by Abbott Laboratories to detect the prothrombin mutation. The method employs a polymerase chain reaction (PCR) amplification and the Abbot LCx microparticle enzyme immunoassay (MEIA) for detection. This method is able to detect and identify both homozygous and heterozygous genotypes. RESULTS: Two hundred ninety-six patients with a history of deep venous thrombosis, pulmonary embolism, preeclampsia, or cardiovascular disease and 163 control patients were included in this study. The prevalence of the mutation was 5.74% in the high-risk group and 3.06% in the control group. There was complete agreement between the results from the MEIA detection with those obtained using other detection methodologies, namely standard PCR and restriction fragment length polymorphism (RFLP) analysis. CONCLUSIONS: The MEIA detection method of the prothrombin mutation represents a simple, fast, and reliable alternative to standard methods of detection and is well suited for use in routine clinical laboratories. The results of our study confirm others' studies showing a greater incidence of G20210A prothrombin gene mutation in patients with an increased risk of venous thrombosis and pulmonary embolism as well as patients with cardiovascular disease and pregnant women with preeclampsia. It reinforces the necessity of including the screening for prothrombin mutation in populations at risk.     

Mutation of a 5,10-methylenetetrahydrofolate reductase gene in systemic lupus erythematosis and antiphospholipid syndrome

AIM: To study prevalence of mutation C677T in gene 5.10-MTHFR in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) as well as in persons free of symptoms of systemic diseases of the connective tissue. MATERIAL AND METHODS: 85 patients participating in the study were divided into three groups: those with SLE (n = 17), with SLE + APS (n = 42), with primary APS (n = 26). The control group consisted of 30 persons without SLE or APS. 55% of the examinees had thrombotic complications of different location. The diagnosis of the mutation was made using DNA isolated from the peripheral blood with standard methods and polymerase chain reaction. Allele (homozygous or heterozygous) condition of the mutation was confirmed by means of allele-specific primers. RESULTS: Mutation C677T in MTHFR gene was found in 40 of 85 patients (47%); 11(27.5%) had a homozygous variant, 29(72.5%)--heterozygous. C677T mutation occurred in 5 of 17 SLE patients (29%), it was in all the cases heterozygous. In primary and secondary APS mutation was detected in 51.5% (35 of 68 patients). Recurrent thrombosis occurred more frequently in patients with mutation MTHFR. Three and more episodes of thrombosis were registered in 17 of 40 patients with mutation C677T against 9 of 44 patients without the mutations (p = 0.04). CONCLUSION: Relationship between elevated blood levels of APL and MTHFR mutation points to the fact that this genetic marker is an additional thrombogenic factor in APS. Mutation C677T in MTHFR gene in APS patients correlates with recurrent thrombosis.     

急性髓系白血病cebpa基因突变研究

本研究旨在探讨急性髓系白血病(AML)患者中cebpa基因突变的发生率及突变情况。选取22例初发或复发的正常核型AML患者,其中M12例,M215例,M52例,M63例例,女性8例,中位年龄48岁(13-71岁)。以基因组DNA为模板,分两段扩增cebpa基因,PCR产物通过直接测序或克隆测序法检测cebpa突变情况。结果表明:22例AML患者中有4例检出cebpa基因突变,突变率为18.2%(4/22),均为M2,其中2例为初发AML患者,2例为复发AML患者。突变主要为N端的无义突变和C端的框内突变。结论:采用PCR扩增联合测序检测cebpa基因突变,主要见于M2型,其预后意义有待进一步研究。     

拉米夫定耐药慢性乙型肝炎患者HBVP区基因突变模式与临床特征

目的分析慢性乙型肝炎患者在拉米夫定（LAM）治疗过程中出现耐药后,HBVP区基因突变模式及临床特征。方法对2009年4月～2009年12月在石家庄市第五医院就诊的116例临床诊断为LAM耐药慢性乙型肝炎患者进行HBVP区基因序列测定。结果116例临床诊断为LAM耐药患者血清HBVDNA水平为（5．34±1．21）log10拷贝／mL,ALT为（135±89）U／L,60．7％（70／116）的患者出现ALT升高。116例患者均出现基因耐药突变,共有7种突变模式,94．8％（110／116）发生YMDD基序突变,其中单纯YMDD突变占22．4％（26／116）,YMDD联合rtLl80M突变占72．4％（84／116）,5．2％（6／116）发生单纯rtLl80M突变。rtM204V联合rtLl80M突变的发生率为87．5％（56／64）,rtM204I联合rtLl80M突变的发生率为69．4％（50／72）,差异有显著统计学意义（P=0．04）。LAM耐药时,4种突变类型即rtM204I、rtLl80M＋rtM204V、rtLl80M＋rtM2041和rtLl80M＋r[IⅥ204V／I患者血清HBeAg、HBVDNA、ALT水平之间差异无统计学意义,P值分别为0．63,O．72,0．82。结论YMDD基序突变是LAM耐药后HBVP区基因突变的主要模式,rtM204V多以联合rtLl80M突变的形式存在,LAM耐药后患者肝组织损伤程度以及病毒复制水平可能与HBVP区突变类型无关。