Molecular genetics of migraine headaches: a review

Following the recent discovery of neural calcium channel mutations in familial hemiplegic migraine, genetic linkage and association studies have been performed world‐wide in an effort to unveil the genetic basis of the more common types of migraine too. Mutations in neural calcium channels, rnitochondrial DNA, serotonin receptors and transporter, dopamine receptors and genetic prothrombotic risk factors have been especially investigated and are discussed here. No unambiguous conclusions have, however, been reached. FHM remains an isolated success story in the quest for the genetic basis of migraine.     

A review of the genetic relation between migraine and epilepsy

A possible relation between migraine and epilepsy has been a matter of debate for many decades. Clinical, epidemiological and therapeutic similarities may be coincidental and are no proof of a common aetiological background. However, a genetically determined dysfunction of ion channels seems to point to a common underlying mechanism for both paroxysmal disorders. For example, mutations in the three known genes for familial hemiplegic migraine can cause epilepsy. It is likely that the development of specific drugs aimed at restoring ion-channel function and/or related cellular signalling pathways might benefit patients with epilepsy as well as those with migraine. This review will briefly summarize the clinical, epidemiological, pathophysiological and therapeutic similarities between migraine and epilepsy. Most attention will be paid to the genetic relationship between these two paroxysmal disorders.     

Effect of glucose/insulin infusion and magnesium supplementation on serum and muscle sodium and potassium and muscle [3H]ouabain binding capacity in Type 1 diabetes mellitus

Glucose has recently been found to decrease muscle potassium content. The aim of this study was to evaluate the effect of the infusion of glucose and insulin and the effect of magnesium supplementation on serum and muscle sodium and potassium and muscle [³H]ouabain binding capacity in patients with Type 1 diabetes mellitus and in controls. Muscle potassium and sodium content, muscle [³H]ouabain binding capacity and serum potassium and sodium concentrations were determined in 10 patients with Type 1 diabetes mellitus and in 5 controls before and after an euglycaemic, hyperinsulinaemic clamp, and after an intravenous magnesium load test. Nine of the patients with Type 1 diabetes mellitus were restudied after 24 weeks of oral magnesium oxide supplementation. Basic serum and muscle sodium and potassium and muscle [³H]ouabain binding capacity did not differ between groups. The infusion of glucose and insulin reduced muscle potassium content, whereas muscle sodium content was unchanged. There were no differences between groups. Oral magnesium oxide supplementation increased muscle potassium content by 6%. Muscle [³H]ouabain binding capacity was unchanged. In patients with Type 1 diabetes mellitus, the intravenous infusion of magnesium increased serum potassium concentration before but not after oral magnesium oxide supplementation. In controls, the infusion of magnesium did not affect serum potassium concentration. It was found that intravenous infusion of glucose and insulin decreases muscle potassium content, probably by shifting potassium from the muscle cells to the splanchnic organs. Oral magnesium oxide supplementation increases muscle potassium content in patients with Type 1 diabetes mellitus. The increase in serum potassium concentration owing to the intravenous infusion of magnesium could be used in the evaluation of magnesium status in patients with Type 1 diabetes mellitus. This, however, requires further investigation.     

Migraine headache: a review of the molecular genetics of a common disorder

This tutorial summarises the state-of-the-art on migraine genetics and looks at the possible future direction of this field of research. The view of migraine as a genetic disorder, initially based on epidemiological observations of transmission of the condition within families, was subsequently confirmed by the identification of monogenic forms of “syndromic” migraine, such as familial hemiplegic migraine. We are currently witnessing a change in the way genetic analysis is used in migraine research: rather than studying modalities of inheritance in non-monogenic forms of migraine and in the persistent modalities of migraine headache, researchers are now tending to focus on the search for genetic markers of dysfunction in biological systems. One example of the evolution of migraine genetic research is provided by the recent efforts to shed light on the pharmacogenomic mechanisms of drug response in migraineurs. In addition, novel molecular approaches about to be introduced are expected to further increase knowledge on this topic and improve patient management.     

Protection against β adrenoceptor agonist reduction of plasma potassium in severe but not in moderate hypokalemia

K-depleted and control rats were anesthetized and infused with terbutalin. In controls, plasma K concentration (pK) decreased by 0.7 mm (P = 0.01). In moderate hypokalemia terbutalin-induced decrease in pK was reduced by 0.3 mm for each 1 mm decrease in pK (n = 8, R(2) = 0.82, P = 0.002) and by 0.2 mm for each 10 mmol/g wet wt. decrease in muscle K content (n = 8, R(2) = 0.66, P = 0.01). Hence, for baseline pK of 4, 3 and 2 mm, decrease in pK was 0.7, 0.4 and 0.1 mm, respectively. In severe hypokalemia (1.7 mm), terbutain induced no further reduction in pK. The combined infusion of insulin and terbutalin showed no additive effect. Normalization of pK by KCl infusion in severe hypokalemia immediately abolished protection against terbutalin induced further pK reduction. Hence, terbutalin clamped pK at around 4 mm, whereas it continued to increase to around 5 mm without terbutalin infusion. Major new findings are: Protection against terbutalin induced further reduction in pK in severe pre-existing hypokalemia (<2 mm) and blunted but nevertheless severe further reduction in pK in more moderate pre-existing hypokalemia; immediate abolishment of protection by normalization of pK; protection against additive reduction in pK by terbutalin and insulin in severe hypokalemia. It may be advisable to avoid hypokalemia when using β adrenoceptor agonists and to maintain pK in the upper normal range if at the risk of arrhythmia.     

The evolving understanding of the analgesic mechanism of action of flupirtine

What is known and Objective: Flupirtine is a widely known analgesic drug that is approved for the treatment of acute and chronic pain, particularly musculoskeletal pain. However, it is neither an NSAID nor an opioid. Given pending trials of flupirtine for the treatment of fibromyalgia pain, an understanding of flupirtine’s (unique?) mechanism of analgesic action is of both clinical and basic science interest. Our objective was to trace the evolution of the understanding of flupirtine’s mechanism of analgesic action to its current status. Methods: Information was gathered from various bibliographic sources, such as PubMed and others, and integrated for insight into postulated mechanism(s) of analgesic action of flupirtine. Results and Discussion: The major site of action of flupirtine appears to be the central nervous system (both spinal and supraspinal). Initial studies suggested involvement of descending adrenergic pathways, followed by a postulated (indirect) action at N‐Methyl‐D‐aspartate (NMDA) receptors, to the present view of activation of a G‐protein regulated inwardly rectifying K⁺ (GIRK) ion channel. The mechanism and relative contribution of metabolites (such as the active acetylated moiety) has not been fully defined. What is new and Conclusion: Flurpirtine might represent a novel class of analgesic agent. As such, it could be useful for the treatment of types of pains normally not amenable to conventional (NSAID or opioid) pharmacotherapy. It could also spawn new avenues of analgesic drug discovery efforts.     

Neuropharmacological effects of lipoic acid and ubiquinone on δ‐aminolevulinic dehydratase,Na+, K+‐ATPase,and Mg2+‐ATPase activities in rat hippocampus after pilocarpine‐induced seizures

In this study, we investigated the effects of lipoic acid (LA) in the hippocampus oxidative stress caused by pilocarpine‐induced seizures in adult rats. Wistar rats were treated with 0.9% saline (i.p., control group), LA (10 mg/kg, i.p., LA group), ubiquinone [20 mg/kg, i.p., ubiquinone (UQ) group], pilocarpine (400 mg/kg, i.p., P400 group), and the association of LA (10 mg/kg, i.p.) plus pilocarpine (400 mg/kg, i.p.) or UQ (20 mg/kg, i.p.) plus pilocarpine (400 mg/kg, i.p.), 30 min before of administration of P400 (LA plus P400 group and UQ plus P400 group, respectively). After the treatments, all groups were observed for 1 h. The enzyme activities (δ‐aminolevulinic dehydratase (δ‐ALA‐D), Mg²⁺‐ATPase, and Na⁺, K⁺‐ATPase) were measured using spectrophotometric methods, and the results compared to values obtained from saline and pilocarpine‐treated animals. Protective effects of LA and UQ were also evaluated on the same parameters. We reported here for the first time that Na⁺, K⁺‐ATPase and δ‐ALA‐D activities inhibition and Mg²⁺‐ATPase stimulation in the pilocarpine model are probably attributed to the oxidative stress caused by seizures in the rat hippocampus. The addition of the antioxidants LA and UQ may reverses the previously mentioned Na⁺, K⁺‐ATPase and δ‐ALA‐D inhibitions and Mg²⁺‐ATPase stimulation. Conclusions: The oxidative stress plays an important signaling role in pilocarpine‐induced seizures, and antioxidant drugs might be considered as therapeutical tools in this pathology.     

α-甘露糖苷贮积症的分子遗传学及其在临床诊断与防治方面的意义

MAN281基因突变导致α-甘露糖苷酶缺乏或活性降低是引起α-甘露糖苷贮积症的根本内因。对MAN2BI基因、LAMAN酶的结构和功能的研究、基因型与表现型的相关性研究以及诊防治方面的研究近年来都取得了诸多新进展。本文重点围绕这几方面作一综述。     

The unique contribution of ion channels to platelet and megakaryocyte function

Summary. Ion channels are transmembrane proteins that play ubiquitous roles in cellular homeostasis and activation. In addition to their recognized role in the regulation of ionic permeability and thus membrane potential, some channel proteins possess intrinsic kinase activity, directly interact with integrins or are permeable to molecules up to ≈1000 Da. The small size and anuclear nature of the platelet has often hindered progress in understanding the role of specific ion channels in hemostasis, thrombosis and other platelet‐dependent events. However, with the aid of transgenic mice and ‘surrogate’ patch clamp recordings from primary megakaryocytes, important unique contributions to platelet function have been identified for several classes of ion channel. Examples include ATP‐gated P2X1 channels, Orai1 store‐operated Ca²⁺ channels, voltage‐gated Kv1.3 channels, AMPA and kainate glutamate receptors and connexin gap junction channels. Furthermore, evidence exists that some ion channels, such as NMDA glutamate receptors, contribute to megakaryocyte development. This review examines the evidence for expression of a range of ion channels in the platelet and its progenitor cell, and highlights the distinct roles that these proteins may play in health and disease.     

The target-specific transporter and current status of diuretics as antihypertensive

The currently available diuretics increase the urinary excretion of sodium chloride by selective inhibition of specific sodium transporters in the loop of Henle and distal nephron. In recent years, the molecular cloning of the diuretic-sensitive sodium transporters at distal convoluted tubule has improved our understanding of the cellular mechanisms of action of each class of diuretics. Diuretics are tools of considerable therapeutic importance. First, they effectively reduce blood pressure. Loop and thiazide diuretics are secreted from the proximal tubule via the organic anion transporter-1 and exert their diuretic action by binding to the Na(+)-K(+)-2Cl(-) co-transporter type 2 in the thick ascending limb and the Na(+)-Cl(-) co-transporter in the distal convoluted tubule, respectively. Recent studies in animal models suggest that abundance of these ion transporters is affected by long-term diuretic administration. The WHO/ISH guidelines point out that diuretics enhance the efficacy of antihypertensive drugs and will most often be a component of combination therapy.     

软骨发育不全植入前遗传学诊断的方法学研究

目的：针对软骨发育不全（ACH）高危家系的 FGFR3基因的突变类型（c.1138G 〉 A, p.G380R）,建立多种快速特异、行之有效的植入前遗传学诊断（PGD）方法,为实施该 ACH 家系的 PGD创造必要的前提条件。方法在确诊该 ACH 患者特定突变类型的基础上,首先用外周血建立各种PGD方法,包括： A.直接测序法; B. ARMS法; C.酶切鉴定法;D. ARMS／RE法。然后对单个卵裂球的全基因组扩增（WGA）产物进行相应方法学的研究。最后,对各种方法进行优化优选。结果 A.直接测序法：正常对照c.1138为G 纯合子,而患者为G／A 杂合峰; B. ARMS 法：正常对照扩增阴性,而患者有445 bp 的特异扩增条带。 C.酶切鉴定法：正常对照酶切后仍为513 bp,而患者酶切后产生205 bp、308 bp、513 bp三条带; D. ARMS／RE法：正常对照扩增阴性,无法做酶切鉴定。而患者有445 bp扩增产物,经SfcI酶切后可产生27 bp和418 bp两个片段。结论本研究已成功建立针对c.1138 G 〉 A 杂合错义突变的直接测序法、ARMS 法、酶切鉴定法和ARMS／RE 法。所建立的4种方法快速、特异,但各有利弊,同时使用可相互弥补,结合STR 连锁分析可把误诊风险降到最低程度。在正常情况下,可在24 h 内完成对ACH高危胚胎的PGD。     

Mass spectroscopic characteristics of low molecular weight proteins extracted from calcium oxalate stones: preliminary study

It is believed that boundary compositions of matrix proteins might play a role in stone formation; however, few proteomic studies concerning matrix proteins in urinary stones have been conducted. In this study, we extracted low molecular weight proteins from calcium oxalate stones and measured their characteristic patterns by mass spectroscopy. A total of 10 stones were surgically removed from patients with urolithiasis. Proteins were extracted from the stones and identified by one-dimensional electrophoresis (sodium dodecyl sulfate buffer [SDS]-polyacrylamide gel electrophoresis [SDS-PAGE]). After in-gel digest, samples were analyzed by the surface-enhanced laser desorption ionization-time of flight (SELDI-TOF) technique. The peptide sequences were analyzed from the data of mass spectroscopy. Proteins were identified from Database Search (SwissProt Protein Database; Swiss Institute of Bioinformatics; http://www.expasy.org/sprot) on a MASCOT server (Matrix Science Ltd.; http://www.matrixscience.com). A total of three bands of proteins (27, 18, and 14 kDa) were identified from SDS-PAGE in each stone sample. A database search (SwissProt) on a MASCOT server revealed that the most frequently seen proteins from band 1 (27 kDa) were leukocyte elastase precursor, cathepsin G precursor, azurocidin precursor, and myeloblastin precursor (EC 3.4.21.76) (leukocyte proteinase 3); band 2 (18 kDa) comprised calgranulin B, eosinophil cationic protein precursor, and lysozyme C precursor; band 3 (14 kDa) showed neutrophil defensin 3 precursor, calgranulin A, calgranulin C, and histone H4. The modifications and deamidations found from the mass pattern of these proteins may provide information for the study of matrix proteins. Various lower molecular weight proteins can be extracted from calcium oxalate stones. The characteristic patterns and their functions of those proteins should be further tested to investigate their roles in stone formation.     

A contemporary perspective on the molecular characteristics of mitochondrial autoantigens and diagnosis in primary biliary cholangitis

Primary biliary cholangitis (PBC) is an autoimmune hepatobiliary disease characterized by immune mediated destruction of the intrahepatic small bile ducts and the presence of antimitochondrial antibodies (AMAs). The mitochondrial autoantigens have been identified as the E2 subunits of the 2-oxo-acid dehydrogenase complex, including the E2 subunits of pyruvate dehydrogenase, branched-chain 2-oxo acid dehydrogenase complex, oxoglutarate dehydrogenase complex, E3 binding protein and PDC E1 alpha subunit. The AMA epitope is mapped within the E2 lipoic acid binding domain, which is particularly important for oxidative phosphorylation. In addition, lipoic acid, which serves as a swinging arm to capture electrons, is particularly susceptible to an electrophilic attack and may provide clues to the etiology of PBC. This review emphasizes the molecular characteristics of AMAs, including detection, immunochemistry and the putative role in disease. These data have significance not only specifically for PBC, but generically for autoimmunity.     

Elucidation of molecular mechanism involved in neuroprotective effect of Coenzyme Q10 in alcohol‐induced neuropathic pain

The aim of the present investigation was to evaluate the effect of Coenzyme Q10 and its combination with vitamin E in alcohol‐induced chronic neuropathic pain. Male Wistar rats were orally treated with alcohol (10 g/kg, 35% v/v, b.i.d.) for 10 weeks. Coenzyme Q10 (25, 50, and 100 mg/kg) and vitamin E (100 mg/kg) were coadministered orally for 1 h after ethanol administration for 10 weeks. Various nerve functions, biochemical, and molecular parameters were assessed. Chronic administration of ethanol for 10 weeks resulted significant development of neuropathic pain. Treatment with Coenzyme Q10 (50 and 100 mg/kg) for 10 weeks showed significant and dose dependently increased in level of nociceptive threshold, endogenous antioxidant, and Na,K‐ATPase enzyme. Coenzyme Q10 (50 and 100 mg/kg) significantly restored the levels of motor nerve conduction velocity and sensory nerve conduction velocity. It also showed significant decrease in levels of endogenous calcium, oxidative–nitrosative stress, TNF‐α, IL‐1β, and IL‐4 level. Alteration in protein expression of polymerase gamma (pol γ) was significantly restored the Coenzyme Q10 treatment. The important finding of the study is that, Coenzyme Q10 (100 mg/kg) and α‐tocopherol (100 mg/kg) combination‐treated rats showed more significant prevention of behavioral, biochemical, and molecular neurotoxic effect of alcohol administration than Coenzyme Q10 or α‐tocopherol alone treated group. It is evident from the finding of present investigation that plethora of mechanism including inhibition of oxido‐nitrosative stress, release of pro‐inflammatory cytokine, modulation of endogenous biomarker, and protection of pol γ protein expression simultaneously orchestrate to exhibits neuroprotective effect of Coenzyme Q10, vitamin E and their combination.     

伴t(8;21)M2型急性髓系白血病患者c-kit和JAK2基因突变分析

目的 研究伴t(8;21)M2型成人急性髓系白血病(AML)患者蛋向酪氨酸激酶家族中c-kit和JAK2基因突变的发生情况、临床特征与预后的关系.方法 采用PCR扩增产物直接测序法检测78例伴t(8;21)M2患者中c-kit基因8号与17号外显子的突变情况;采用等位基因特异性PCR方法 检测患者JAK2 V617F的发生情况.结果 ①78例伴t(8;21)M2患者中27例(34.6%)检测出c-kit基因突变(mac-kit),6例(7.7%)检出JAK2 V617F突变,未见同一患者同时发生mac-kit和JAK2V617F突变. ②c-kit/JAK2 V617F突变型患者的外周血白细胞中位数为23.0(4.4～167.0)×109/L,明显高于野生型c-kit和JAK2患者[14.4(1.6-97.4)×109/L](P<0.05),两组的血红蛋白水平、血小板计数、骨髓原始细胞比例、CD117表达水平以及年龄、性别差异均无统计学意义(P>0.05);c-kit突变型组患者的外周血白细胞中位数为23.1(4.4-167.0)×109/L,与野生型组[16.0(1.6-97.4)×109/L]患者相比,差异有统计学意义(P<0.05);由于JAK2 V617F突变患者仅6例,未单独进行统计学分析. ③c-kit/JAK2 V617F突变组患者的完全缓解率与野生型组相近(分别69.6%与80.0%,P>0.05),但c-kit/JAK2 V617F突变组患者的2年持续完全缓解(CCR)率低于野生型组(分别26.7%与56.1%,P<0.05);两组患者2年总生存率的差异无统计学意义(分别为34.8%与58.6%,P>0.05).结论 蛋白酪氨酸激酶家族的c-kit和JAK2基因突变在伴t(8;21)M2型AML患者中较常见,并且与白细胞数量增高相关;其中c-kit突变更为频繁,但同一类的两种突变一般不会同时出现于同一患者;伴有此类基因突变的患者复发率高,预后较差;筛查此类基凶突变对于今后的靶向治疗以及了解临床预后将有重要意义.     

游离钙和氧合指数联合快速序贯器官衰竭评分在识别成人脓毒症中的诊断效能

目的研究游离钙(iCa)和氧合指数(PaO₂/FiO₂)联合快速脓毒症相关序贯器官衰竭评分(qSOFA)在识别成人脓毒症患者中的诊断效能。方法回顾性分析2019年10月至2021年3月就诊于东部战区总医院抢救室的147例脓毒症患者及158例主要诊断为非脓毒症的感染性疾病患者,收集患者临床资料(包括iCa、PaO₂/FiO₂、qSOFA等指标),通过倾向性评分匹配(PSM)校正患者年龄、性别、感染部位等混杂因素,得到脓毒症组(n=93)和非脓毒症组(n=93)患者,比较PSM前后两组间的临床资料,将匹配后数据集(n=186)作为训练集,采用Logistic回归分析感染性疾病患者发生脓毒症的独立危险因素,通过受试者工作特征曲线下面积(AUC)进行诊断效能分析,比较新发低钙血症、PaO₂/FiO₂、qSOFA及三者联合模型在识别成人脓毒症患者中的诊断效能,将原数据集(n=305)作为验证集代入联合模型进行验证,并比较联合模型与脓毒症相关序贯器官衰竭评分(SOFA)间的差异和一致性。结果PSM前后脓毒症患者iCa、PaO₂/FiO₂均低于非脓毒症组(PSM前:Z=-5.138,Z=-7.743;PSM后:Z=-3.505,Z=-4.817,P<0.001),qSOFA分值高于非脓毒症组(PSM前:Z=-7.089;PSM后:Z=-4.149,P<0.001),iCa与降钙素原(PCT)、C-反应蛋白(CRP)、白细胞介素-6(IL-6)、SOFA及急性生理与慢性健康状况评分系统Ⅱ(APACHEⅡ)呈负相关(r=-0.338、-0.243、-0.271、-0.281、-0.269,P<0.05),联合模型在训练集(n=186)中识别成人脓毒症患者的AUC为0.777,95%CI为0.711~0.835,敏感度为74.19%,特异度为73.12%,阳性似然比为2.76,阴性似然比为0.35,在验证集(n=305)中识别成人脓毒症患者的AUC为0.836,95%CI为0.790~0.876,敏感度为77.55%,特异度为77.85%,阳性似然比为3.50,阴性似然比为0.29,联合模型在训练集及验证集中的AUC大于新发低钙血症、PaO₂/FiO₂及qSOFA分值(P<0.001),与SOFA进行McNemar检验提示P=0.904、一致性检验Kappa值为0.554(P<0.001)。结论新发低钙血症、PaO₂/FiO₂、qSOFA分值与感染性疾病患者发生脓毒症有回归关系,其中新发低钙血症是独立危险因素,与iCa、PaO₂/FiO₂及qSOFA单独使用相比,三者联合模型在识别成人脓毒症中的诊断效能更高。     

乙型肝炎病毒基因型与YMDD基因区序列突变及BCP突变关系探讨

目的 对湘潭地区HBV感染者的基因型、YMDD基因区序列突变及BCP区突变情况进行研究,并对三者之间的关系进行探讨.方法 针对湘潭地区952例不同类型的HBV感染者的样本同时进行基因型、YMDD基因区序列突变及BCP区突变检测,并对检测结果进行统计分析.结果 湘潭地区HBV各种基因型分布比例为:B型698例、占73.32%,C型115例、占12.08%,B、C型混合感染139例、占14.60%.YMDD基因区序列突变结果显示:YMDD野生型844例、占88.66%,其余为YMDD突变型,其中YVDD 54例、占5.67%,YIDD 53例、占5.57%,1例为YMDD与YVDD混合感染.BCP区突变结果显示:1762A/1764G(野生型)672例、占70.59%,1762T/1764A(突变型)188例、占19.75%,其余92例为1762T/1764A和1762A/1764G混合型、占9.66%.基因型、YMDD基因区序列突变及BCP区突变三者相关性分析显示:HBV B型和C型YMDD基因区序列突变率分别为10.04%、10.43%,差异无统计学意义(χ2=0.017,P＞0.05),HBV B型和C型YMDD基因区序列突变类别差异有统计学意义(χ2=4.836,P＜0.05),HBV C型YVDD突变率(9.57%)要高于B型(5.88%).HBV B型和C型BCP区突变率分别为27.36%、46.09%,差异有统计学意义(χ2=16.478,P＜0.01),C型BCP区突变率要高于B型.HBV YMDD野生型和突变型的BCP区突变率分别为2 8.67%、35.51%,差异无统计学意义(χ2=2.139,P＞0.05),但YVDD BCP区突变率(61.11%)要高于其他类别.结论 (1)湘潭地区流行的HBV基因型主要为B型和C型,其中B型为优势基因型,具有南方地区的特点.(2)拉米夫定治疗前通过HBV基因型检测来预测抗病毒应答可能并无实际意义.(3)HBV基因分型、YMDD基因区序列突变、BCP区突变检测的应用,将有助于临床上对乙肝患者的预后和转归进行正确评价,为及时合理的实施干预措施提供了重要依据.

Abstract：

Objective To investigate the relationship between HBV genotypes and YMDD motif mutations or BCP mutations in Xiangtan of Hunan Province. Methods HBV genotypes, YMDD motif mutations and BCP mutations were analyzed in 952 HBV infected patients. Results HBV genotyping showed that 698 HBV type B patients and 115 HBV type C patients accounted for 73.32% and 12.08% respectively of all the participants. The rest 139( 14.60% )were genotype B and C mixed infection( B + C ). The analysis of YMDD motif mutations showed that 844 YMDD wild-type which accounted for 88.66% of all the subjects and the remainder were YMDD mutation types, of which 54( 5.67% ) carried YVDD, 53( 5.57% ) YIDD,and 1 YVDD and YIDD mixed infection. Basic Core Promoter mutations showed that 1762A/1764G ( wild type )accounted for 70.59% and 1762T/1764A( mutant ) accounted for 19.75%. The rest 92 patients were 1762T/1764A and 1762A/1764G mixed infection. This study showed no significant difference in the rate of YMDD mutation( 10.04% vs 10.43% ,χ2 =0.017,P＞0.05 ) ,but a significant difference in the types of YMDD mutation(χ2 = 4.836, P ＜ 0.05 )between HBV types B and C. The YVDD mutation was more commonly seen in genotype C( 9.57% ) than in genotype B( 5.88% ). The BCP mutation rate showed a significant difference( 27.36% vs 46.09%, χ2 = 16.478, P ＜ 0.01 ). Genotype C was more frequent than genotype B. The BCP mutation rate showed no significant difference between YMDD Wild-type and YMDD mutation types( 28.67% vs 35.51%, χ2 = 2.139, P ＞ 0.05 ), but most of BCP mutations happened in YVDD mutant type( 61.11% ). Conclusions ( 1 ) The predominant HBV genotypes in Xiangtan were genotype B and genotype C, the major genotype was type B, which display the characteristics of epidemiology in Southern China. ( 2 ) Determination of HBV genotypes before lamivudine therapy was probably not an important pretreatment investigation to predict antiviral responses. ( 3 ) Detection of HBV genotypes, YMDD motif mutations and BCP mutations will contribute to the correct evaluation of prognosis and timely proper management of HBV patients.