Graves病低钾血症与HLA—DQA1等位基因的关联

目的:探讨天津地区汉族人Graves病(GD)低钾血症与HLA-DQA1等位基因多态性的关系.方法:采用PCR-限制性酶切片段长度多态性分析法(RFLP)测定GD患者及正常对照者的HLA-DQA1等位基因型,计算并比较GD和正常对照组的基因型频率;GD中周期性麻痹患者、非周期性麻痹低血钾患者和正常血钾患者的基因型频率.结果:GD患者HLA-DQA1*0301基因频率明显高于正常对照组(RR=1.577,P<0.05);而HLA-DQA1*0201和HLA-DQA1*0401基因频率明显低于正常对照组(RR=0.395,P<0.05;RR=0.113,P<0.01).GD中周期性麻痹患者、非周期性麻痹低血钾患者与正常血钾患者相比,HLA-DQA1等位基因的基因频率差异无统计学意义(P>0.05).结论:HLA-DQA1*0301可能是天津地区汉族人群GD甲亢的易感基因,而HLA-DQA1*0201和HLA-DQA1*0401可能是天津地区汉族人GD甲亢的保护基因;但未发现GD低钾血症与HLA-DQA1基因有关.     

Graves病甲亢白细胞减少与HLA-DQA1基因多态性的关联性

目的：研究天津地区汉族Graves病甲状腺功能亢进症（GD甲亢）白细胞减少与HLA-DQA1基因多态性的关联。方法：采用限制性片段长度多态性聚合酶链反应（PCR-RFLP）法检测60例GD甲亢白细胞减少患者、60例GD甲亢白细胞正常患者、100例正常对照者的HLA-DQA1基因型，计算和比较3组的HLA-DQA1等位基因频率。结果：（1）GD甲亢患者DQA1^＊0301频率高于对照组（P〈0．05，OR=1．528），而DQAI^＊0201频率和DQAI^＊0401频率低于对照组（P〈0．05，0R=0．474；P〈0．05，OR=0．333）。（2）GD甲亢白细胞减少组DAQI^＊0301高于对照组（P〈0．05，0R=1．737）。而DQAI^＊0201和DQAI^＊0401低于对照组（P〈0．05，OR=0．310；P〈0．05，OR=0．132）。GD甲亢白细胞正常组与对照组差别无统计学意义。结论：HLA-DQAI^＊0301等位基因可能是天津地区汉族人GD甲亢的易感基因，但并非GD甲亢白细胞减少的易感基因；HLA-DQAI^＊0201和HLA-DQAI^＊0401可能是天津地区汉族人GD甲亢的保护基因，但并非GD甲亢白细胞减少的保护基因。     

山西汉族人群HLA-DQ基因多态性分析

目的 分析山西汉族人群HLA-DQA1、HLA-DQB1基因多态性.方法 应用聚合酶链反应-序列特异性引物(PCR-SSP)法对100例山西汉族健康人进行HLA-DQA1、HIA-DQB1基因分型,并与国内部分地区汉族人群进行比较.结果 ①共检出9种HLA-DQA1等位基因型别,分别是:HLA-DQA1*0301/2(24.5%)、*0102(14.0%)、*0103(12.5%)、*0201(12.O%)、*0501(12.O%)、*0104(8.5%)、*0401(8.O%)、*0601(4.5%)、*0101(4.0%).②在100个健康人中共检出13种HIA-DQB1等位基因型别,分别是:HLA-DQB1*0301/4(21.0%)、*0201(18.5%)、*0303(14.5%)、*0302(12%)、*0603/8(9.0%)、*0501(5.5%)、*0401(4.5%)、*0602(4.5%)、*0604(3.5%)、*0503(2.5%)、*0601(2.0%)、*0502(1.5%)、*0402(1.0%).③山西汉族HLA-DQ等位基因分布与北方汉族接近,又有其自身特征.结论 山西汉族人群HLA-DQ基因具有丰富的多态性.其分布特征与北方汉族人群接近,但又有其独特性.     

抗心磷脂抗体阳性脑梗死与HLA-DQA1和HLA-DQB1基因多态性的关系

目的:探讨人类白细胞抗原(HLA)的DQA1和DQB1基因多态性与抗心磷脂抗体(ACA)阳性脑梗死的相关关系.方法:运用聚合酶链式反应-序列特异性引物(PCR-SSP)法对30例抗心磷脂抗体阳性(ACA+)脑梗死患者和90例抗心磷脂抗体阴性(ACA-)脑梗死患者HLA-DQA1和DQB1基因多态性进行分型.结果:2组共检出12对HLA-DQA1和HLA-DQB1等位基因,ACA+脑梗死组患者的DQA1*0301等位基因频率为35.0%,高于ACA-脑梗死组患者的17.7%(P < 0.05);ACA+脑梗死组患者的DQB1*0501等位基因频率为31.7%,高于ACA-脑梗死组患者的16.7%(P < 0.05).结论:DQA1*0301和DQB1*0501等位基因与ACA+脑梗死的易感性相关,可能是ACA+患者脑梗死的易感基因.     

细胞毒性T淋巴细胞相关抗原4基因多态性与抗甲状腺药物所致白细胞减少的相关性

目的:研究中国北方汉族弥漫性毒性甲状腺肿(GD)患者细胞毒性T淋巴细胞相关抗原4(CTLA-4)第1外显子49位点A/G多态性与抗甲状腺药物(ATD)所致白细胞减少的相关性.方法:收集2009年10月至2010年6月到青岛大学医学院附属医院内分泌科就诊的GD患者(GD组)和同期到体检中心查体的健康人群(健康对照组).GD组分为3个亚组:ATD治疗后白细胞减少组、ATD治疗后白细胞正常组和ATD治疗前白细胞减少组.收集所有研究对象外周非抗凝静脉血血凝块,提取基因组DNA,应用聚合酶链反应-限制性片段长度多态性技术测定CTLA-4基因第1外显子49位点基因型,抽取部分样本进行测序,并计算各组的基因型和等位基因频率.结果:GD组211例患者(ATD治疗后白细胞减少组73例,ATD治疗后白细胞正常组86例,GD合并白细胞减少组52例)、健康对照组85例纳入研究.GD组CTLA-4基因第1外显子49位点AA、AG和GG基因型频率分别为2.4％(5例)、38.8％(82例)、58.8％(124例),A、G等位基因频率分别为21.8％、78.2％;健康对照组AA、AG和GG的基因型频率分别为15.3％(13例)、32.9％(28例)和51.8％(44例),A和G的等位基因频率分别为31.8％和68.2％;2组的基因型和等位基因频率差异有统计学意义(x2 =17.74,P=0.000 1;x2 =6.48,P=0.01).CTLA-4基因第1外显子49位点基因型和等位基因频率在ATD治疗后白细胞减少组、ATD治疗后白细胞正常组和GD合并白细胞减少组之间差异均无统计学意义(均P ＞0.05).结论:中国北方汉族人群GD发病与CTLA-4基因第1外显子49位点A/G多态性相关,而ATD导致的白细胞减少似乎与其多态性无关.     

儿童Graves病与CTLA-4基因多态性研究

Graves病(简称GD)是一种常见的器官特异性自身免疫性甲状腺疾病.近年来儿童GD与成人GD一样有发病率逐渐增高的趋势,已成为一种危害儿童健康的常见病.其确切病因不明,但已肯定GD是一种多基因遗传的自身免疫性疾病.最新研究认为候选基因中HLA和CTLA-4 2个基因位点占GD遗传易感性的50%,而CTLA-H4基因作为T细胞活化的一种重要的负性调节因子,已成为导致自身免疫性内分泌疾病的一个非常重要的易感位点[1-2],也成为国内外学者研究的热点,儿童起病的GD与成人起病的GD在发病机制上截然不同,本研究旨在探讨CTLA-4基因第2外显子多态性与天津市儿童GD的相关性.     

Graves病白细胞减少与CTLA-4基因多态性的相关性

目的：探讨天津地区汉族人Graves病（GD）合并白细胞减少，与细胞毒性T淋巴细胞相关抗原-H4（CTLA-4）基因外显子1第49位点A／G和启动子-318位点C／T二态性的相关性。方法：运用PCR—RFLP技术分析40例GD白细胞减少患者、56例GD白细胞正常患者及60例正常人CTLA-4基因、外显子1第49位点和启动子-318位点基因型．计算并比较各组基因型和等位基因频率。结果：GD组第1外显子第49位点基因型GG和等位基因G的频率明显高于正常对照组，3组人群的CTLA-4基因启动子-318位点的基因型与等位基因的分布差别无统计学意义。GD白细胞减少组与GD白细胞正常组之间基因型、等位基因的分布差别无统计学意义。结论：CTLA-4基因外显子1G49可能是天津地区汉族人Graves病的易感基因，而其与启动子-318位点可能不是天津地区汉族人GD合并白细胞减少的易感基因。     

细胞间粘附因子1基因多态性与Graves病的相关性研究

目的探讨细胞间粘附因子1（Intercellular adhesion molecule,ICAM-1）基因第4外显子G241R（721G→A）与第6外显子K469E（1405A→G）多态性与中国北方汉族人Graves病（GD）的相关性。方法运用聚合酶链反应-序列特异性引物（PCR-SSP）技术,检测了202例中国北方汉族人的血清sI-CAM-1水平和ICAM-1基因第4外显子G241R（721G→A）与第6外显子K469E（1405A→G）多态位点的等位基因和基因型,其中初诊Graves病患者139例,按发病年龄分为早发GD组（发病年龄〈40岁,78例〉和晚发GD组（发病年龄≥40岁,61例）两个亚组;健康对照组63例。应用统计软件SPSS11.0分析,各组间的等位基因频率和基因型比较用卡方检验。结果①ICAM-1基因第4外显子721G→A多态位点存在G、A两种等位基因和GG、GA、AA三种基因型;②ICAM-1基因第6外显子1405A→G多态位点存在A、G两种等位基因和AA、AG、GG三种基因型;③ICAM-1基因第4外显子721G→A多态位点的A等位基因和GA基因型频率在早发GD组高于晚发GD组和健康成人组。结论①中国北方汉族人ICAM-1基因第4外显子存在721G→A多态,A等位基因可能是早发GD的易感等位基因;②中国北方汉族人ICAM-1基因第6外显子存在1405A→G多态,但这种基因多态变化与GD患者发病年龄无相关性。     

细胞毒性T淋巴细胞相关抗原4基因多态性与甲巯咪唑致Graves病患者肝损害的相关性

目的探讨细胞毒性T淋巴细胞相关抗原4(CTLA-4)基因多态性与甲巯咪唑(MMI)致山东地区汉族Graves病(GD)患者肝损害的相关性。方法研究对象选自2011年3月至2012年4月到青岛大学医学院附属医院内分泌科就诊或住院的GD患者(GD组)和同期到体检中心查体的健康人(健康对照组)。GD组分为3个亚组:单纯性GD组、MMI致肝损害组和甲亢性肝损害组。收集受试者外周非抗凝静脉血血凝块,提取基因组DNA,应用聚合酶链反应-限制性片段长度多态性技术测定CTLA-4基因第一外显子49位点和启动子区-318位点基因型,计算各组的基因型和等位基因频率。结果共收集到GD患者160例,其中单纯性GD组65例,男10例,女55例,平均年龄(40.4±14.4)岁;MMI致肝损害组40例,男11例,女29例,平均年龄(40.5±13.7)岁;甲亢性肝损害组55例,男9例,女46例,平均年龄(38.0±12.9)岁。健康对照组64例,其中男20例,女44例,平均年龄(40.7±10.7)岁。各组性别、年龄差异无统计学意义(P>0.05)。GD组和健康对照组CTLA-4基因第一外显子49位点AG+GG基因型频率分别为91.9%(147/160)和78.1%(50/64),G等位基因频率分别为74.4%(238/320)和59.4%(76/128),组间差异有统计学意义(χ2=8.153,P=0.004;χ2=6.259,P=0.012);启动子区-318位点的CT+TT基因型和T等位基因频率分布组间差异无统计学意义(P>0.05)。GD组的3个亚组之间两两比较,CTLA-4基因第一外显子49位点AG+GG基因型和G等位基因频率,启动子区-318位点CT+TT基因型和T等位基因频率差异均无统计学意义(均P>0.05)。结论 CTLA-4基因第一外显子49位点及启动子区-318位点多态性与山东地区汉族人群MMI所致肝损害无明显相关性,第一外显子49位点A/G多态性与GD的发生可能相关。     

功能性BRCA1启动子c.-2265C/T多态性与卵巢癌易感性的相关性

目的 探讨BRCA1基因功能性启动子c.-2265C/T多态性与卵巢癌易感性的关联性.方法 应用MGB-TaqMan探针等位基因分型技术对123例上皮性卵巢癌患者(病例组)和123例与之年龄相匹配的健康汉族妇女(对照组)的外周血基因组DNA进行BRCA1功能性启动子c.-2265C/T单核苷酸多态性(SNP)基因型的检测,并进行相关性分析.结果 病例组中,CC基因型44例(35.8％),CT基因型62例(50.4％),TT基因型17例(13.8％);对照组中,CC基因型45例(36.6％),CT基因型60例(48.8％),TT基因型18例(14.6％);组间比较无统计学差异(P＞0.05).与CC基因型相比,TT基因型与降低卵巢癌中低分化腺癌、子宫内膜样癌及浆液性腺癌发病风险均无明显相关性(P＞0.05).结论 与C等位基因比较,T等位基因的纯合型未降低上皮性卵巢癌的发病风险.     

抗流感病毒H1N1海绵放线菌的筛选及菌株HA10201的鉴定

目的从海绵中分离筛选具有抗H1N1活性的放线菌,并对活性菌株HA10201进行鉴定。方法采用CPE和MTT方法对从海绵中分离的放线菌进行抗H1N1活性筛选,对活性较强的菌株HA10201进行形态学和生理生化特性研究,测定其16SrDNA序列并进行系统发育分析。结果菌株HA10201发酵液稀释20倍后对H1N1抑制率达68.1%,HA10201与Streptomyces roseorubens的形态和生理生化特征最为接近,且与其16SrDNA序列相似性为99.40%,且在发育树上聚为一个分支。结论菌株HA10201鉴定为S.rose-orubens,其发酵液具有较强的体外抗H1N1活性,值得进一步研究。     

人类白细胞抗原-DQA1区基因多态性与血友病A患者凝血因子Ⅷ抑制物的相关性研究

目的探讨人类白细胞抗原（HLA）-DQA1区基因多态性与血友病A患者凝血因子Ⅷ（FⅧ）抑制物发生的相关性。方法采用聚合酶链反应一序列特异性引物技术（PCR—SSP）,对130例HA患者和90名健康对照者的HLA-DQA1区基因多态性进行检测。采用Bethesda法检测HA患者FⅧ抑制物活性。结果130例HA患者中．检出6例FⅧ抑制物阳性患者（全部为重型）,占重型患者的6．8％;对所检测FⅧ抑制物阳性患者HLA—DQA1区的各等位基因,占全部HA患者的等位基因阳性率及其在重型HA患者的等位基因阳性率作比较,差异无统计学意义（P值均〉0．05）。结论尚不能证明该区各等位基因与抑制物发生具有相关性。     

Abnormal gangliosides in the plasma of alcoholics

Gangliosides were isolated from plasma of alcoholics. The pattern of gangliosides was compared with that of healthy humans. Up to seven fractions of gangliosides could be detected. In healthy subjects the following pattern was found: GM3 38.2%, SPG 6.0%, GD3 30.2%, GD1a 10.6%, GD1b 4.8%, GT1b 7.9%, GQ1b 2.2%. In alcoholics, significant differences were observed in the main ganglioside fractions GM3 (52.6%) and GD3 (17.5%).     

Macrophage-derived soluble CD163 level in young patients with Gaucher disease: Relation to phenotypes,disease severity and complications

ObjectivesBone and lung involvement are two major causes of morbidity in Gaucher disease (GD). The soluble form of CD163 (sCD163) is a valuable diagnostic biomarker for monitoring diseases with increased macrophage activation. We determined sCD163 levels in 30 children and adolescence with GD compared with 30 healthy controls and assessed the relation to phenotypes, disease severity and complications.MethodsThirty GD patients (10 had type 1 and 20 had type 3) were studied stressing on skeletal, pulmonary or neurological manifestations, enzyme replacement therapy (ERT), hematological profile, plasma chitotriosidase activity, D-dimer and sCD163. Liver and spleen volumes and bone mineral density (BMD) were assessed.ResultssCD163 levels were markedly elevated in patients compared with controls. D-dimer, chitotriosidase activity and sCD163 levels were significantly increased in type 3 GD patients compared with type 1. sCD163 was significantly elevated in GD patients with dysphagia, developmental delay, pulmonary hypertension risk or abnormal BMD (osteopenia/osteoporosis) than those without. GD patients receiving ERT every 2 weeks had lower levels than those under ERT for more than 2 weeks. sCD163 was positively correlated with age, disease duration, severity score index, D-dimer and chitotriosidase activity. The cutoff value of sCD163 at 9400 ng/mL could differentiate GD patients with and without pulmonary hypertension risk with a sensitivity of 90% and specificity of 95%.ConclusionssCD163 is a biomarker for the clinical assessment of macrophage proliferation and activity that would help in risk prediction of bone and lung involvement and monitoring treatment response.     

Age-dependent changes in liver ganglioside levels

Gangliosides, sialic acid-containing glycosphingolipids, are found in the outer layer of the plasma membrane of all vertebrate tissue cells; the highest concentration is in the central nervous system. In recent years, there has been research on the distribution and quantity of gangliosides in extra-neuronal tissues, such as liver, kidney and intestine. Since liver is the main source of gangliosides that are carried by lipoproteins in the blood, we examined the effect of development and aging on gangliosides in liver tissue. The relationship was investigated between GM1, GD3, GD1a, GD1b, GT1b ganglioside fractions and the aging process in liver tissue of Wistar-Albino rats aged 3, 6, 12 and 24 months. HPLC analysis of liver gangliosides showed the following results: Compared to 3 month-old rats, the GM1 fraction was decreased by 50% in 6 month-old rats, increased in 12 month-old rats and decreased in 24 month-old rats. The GD3 and GD1b fractions increased until 12 months of age and were decreased significantly (p < 0.01) in 24 month-old rats. The GD1a ganglioside fraction was significantly increased in 6 and 24 month-old rats (p < 0.01). We concluded that the increment of the polar fractions, such as GD3 and GD1b, and the variations of the other fractions in the plasma membrane of the hydrophilic liver tissue during the first 12 months were important parameters.     

Diosgenin relieves goiter via the inhibition of thyrocyte proliferation in a mouse model of Graves＇ disease

Aim： To investigate the effects of diosgenin （Dio）, a naturally occurring steroid saponin, on goiter formation in a mouse model of Graves’ disease （GD） and the underlying mechanisms.
Methods： Female BALB/c mice were injected with adenovirus expressing the A subunit of thyrotropin receptor to induce GD. The mice were treated with Dio （20, 100 mg·kg-1·d-1, ip） for 12 or 24 d. The serum levels of TT4 and TRAb were examined using radioimmunoassay and electrochemiluminescence. The size and morphology of thyroid glands were examined. Thyrocyte proliferation was determined using BrdU incorporation assay. The expression of proliferation-associated proteins IGF-1, NF-κB, cyclin D1, and PCNA in thyroids was analyzed using immunohistochemistry and real-time PCR.

Results： The GD mice showed significantly high serum levels of TRAb and TT4 compared to the normal mice. Treatment of the GD mice with Dio for 24 d dose-dependently reduced the TT4 level and thyroid size, but did not affect the abnormal level of TRAb. Furthermore, Dio treatment dose-dependently reversed the morphological changes and reduced excessive thyrocyte proliferation in thyroids of the GD mice. Dio treatment also dose-dependently reduced the mRNA and protein levels of IGF-1, NF-κB, cyclin D1, and PCNA in thyroids of the GD mice.

Conclusion： Dio relieves goiter in a mouse model of GD through the inhibition of thyrocyte proliferation. The mechanisms involve the suppression of IGF-1, NF-κB, cyclin D1, and PCNA expression.     

Graves’ disease could increase polycystic ovary syndrome and comorbidities in Taiwan

Abstract

Background: To investigate the association between Graves’ disease (GD) and polycystic ovary syndrome (PCOS) and its comorbidities.

Methods: Logistic regression was performed to determine the association between the two conditions. Cumulative incidence curves were obtained using the Kaplan–Meier method and log-rank test. Hazard ratios were determined using the Cox proportional hazards regression model.

Results: We included 5399 patients with GD as the study group and 10,798 patients without GD as the control group. The cumulative incidence curve of PCOS in patients with GD was significantly higher than that in patients without GD (p?=?.02). The adjusted hazard ratio for PCOS in patients with GD compared with patients without GD was 1.47 (95%CI = 1.09–1.98). The adjusted odds ratio of hyperlipidemia in patients with GD and PCOS was 2.18 (95%CI = 1.14–4.17) higher than that in patients with GD only.

Conclusion: Our study demonstrated that women with GD could be at risk of developing PCOS; additionally, a higher incidence of comorbidities, including hyperlipidemia, was noted in women with GD and PCOS.