广西壮族自治区妊娠期糖尿病与人类白细胞抗原Ⅱ类基因多态性的关系

目的探讨广西壮族自治区人类白细胞抗原(HLA)-Ⅱ类基因多态性与妊娠期糖尿病的相关性。方法选取妊娠期糖尿病(GDM)孕妇100例作为试验组,100例糖耐量正常的孕妇作为对照组,采用序列特异性引物聚合酶链反应(PCR)对2组孕妇的HLA-Ⅱ类基因进行检测和分析。结果 2组孕妇经基因检测后,GDM组等位基因DQA1*0301、DRB1*0301和DRB1*1302的频率显著高于对照组,差异具有统计学意义(P<0.05);DQA1*0103、DQA1*0501和DQB1*0601等位基因的频率低于对照组,但差异无统计学意义(P>0.05),DQB1*0201、DQB1*0302、DQB1*0602等位基因的频率高于对照组,但差异也无统计学意义(P>0.05)。结论在广西壮族自治地区,HLA-Ⅱ类等位基因与GDM的发病存在相关的联系,等位基因DRB1*0301、DRB1*1302和DQA1*0301是妊娠期糖尿病的易感基因。     

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.     

HLA—DQB1等位基因与广东汉族人群系统性红斑狼疮相关性研究

应用微量序列特异性引物聚合酶链反应技术（Micro—PCR—SSP）,探讨我国广东籍汉族人群系统性红斑狼疮（SEE）与HLA-DQB1基因的相关性。对38例SEE患者和110例正常对照者的血样进行分析,实验表明,SEE患者DQB1＊0601等位基因频率显著升高（RR=2．19,P=0．0055）,可能是易感基因,而DQB1＊0301与DQB1＊0401基因频率则显著降低（DQB1＊0301,RR=0．1253,P=0．0001;DQB1＊0401,RR=0,P=0．0409）,可能为保护基因。     

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.     

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.     

K562白血病细胞系HLA-II等位基因型

目的:测定K562白血病细胞系HLA -II等位基因型。方法:采用聚合酶链反应 -限制性片断长度多态性技术对K562白血病细胞系HLA -II类抗原基因进行DNA分型。结果:K562细胞系的HLA -II基因型均为纯合子型 ,等位基因分别是 :DRB1*0301/*0301,DQB1*0201/*0201,DPB1*0402/*0402。结论:提高对K562白血病细胞系HLA -II基因型的认识,可为髓系白血病分子免疫遗传学基因型研究提供初步的检测资料     

K562 白血病细胞系HLA-Ⅱ等位基因型

目的：测定K562白血病细胞系HLA—Ⅱ等位基因型。方法：采用聚合酶链反应—限制性片断长度多态性技术对K562白血病细胞系HLA—Ⅱ类抗原基因进行DNA分型。结果：K562细胞系的HLA—Ⅱ基因型均为纯合子型，等位基因分别是：DRB1^*0301／^*0301，DQB1^*0201／^*0201，DPB1^*0402／*0402。结论：提高对K562白血病细胞系HLA—Ⅱ基因型的认识，可为髓系白血病分子免疫遗传学基因型研究提供初步的检测资料。     

HLA-DRB1、HLA-DQB1基因多态性与云南汉族人群耐多药肺结核病的关联研究

摘要：目的:探讨云南地区汉族人群HLA-DRB1、HLA-DQB1基因多态性与耐多药肺结核病发生的关系。方法:收集2017～2018年在我院就诊的云南省汉族耐多药肺结核（MDR-PTB）患者300例作为观察组;门诊体检健康人群300例作为对照组。应用聚合酶链式反应-直接测序基因分型法（PCR-SBT）,检测两组人群HLA-DRB1、HLA-DQB1等位基因分布频率。结果:共检测到25个HLA-DRB1等位基因,17个HLA-DQB1等位基因。其中观察组的HLA-DRB1*07:01等位基因频率显著性高于对照组[18.7%vs.13.5%,P=0.007,OR=1.471,95%CI（1.077,2.008）],观察组的HLA-DQB1*03:01等位基因频率显著性高于对照组[27.8%vs.20.3%,P=0.002,OR=1.511,95%CI（1.157,1.974）],其余等位基因两组间无明显差异（P>0.05）。结论:HLA-DRB1*07:01和HLA-DQB1*03:01等位基因可能是云南汉族人群耐多药肺结核的易感基因。     

新疆维吾尔族患者CYP2C9和VKORC1基因多态性分布及不同种族间的比较

目的:为建立适合新疆维吾尔族患者的华法林个体化给药模型提供研究基础。方法:检测200例新疆维吾尔族患者中CYP2C9和VKORC1的基因型,并与世界不同种族人群基因型及等位基因频率进行比较。结果:新疆维吾尔族CYP2C9*1/*1基因型频率低于韩国、日本、美国及中国汉族,高于土耳其;*1/*2杂合突变型频率低于土耳其、瑞典、英国,高于韩国、日本及中国汉族;*1/*3杂合突变型频率高于日本、韩国、中国汉族、英国、美国;*3/*3基因频率高于上述人群(P<0.05)。新疆维吾尔族*1等位基因频率低于中国汉族、日本、韩国、美国,高于土耳其;*2等位基因高于中国汉族、日本、韩国,低于土耳其、瑞典、英国;*3等位基因高于中国汉族、日本、韩国、瑞典、英国和美国(P<0.05)。VKORC1-1639AA型频率高于美国、瑞典、英国,低于新加坡、日本、中国台湾、中国汉族;AG型频率高于新加坡、日本、中国台湾、中国汉族;GG型频率高于新加坡、日本、中国台湾、中国汉族,低于美国、瑞典、英国(P<0.05)。新疆维吾尔族A型等位基因频率低于中国汉族、中国台湾、日本、新加坡,高于美国、瑞典和英国;G型等位基因高于中国汉族、中国台湾、日本、新加坡,低于美国、瑞典、英国(P<0.05)。结论:新疆维吾尔族患者CYP2C9和VKORC1基因多态性分布与亚洲及欧美人群均存在明显差异。     

副肿瘤性天疱疮患者人类白细胞抗原-Ⅱ类基因易感性研究

目的 寻找中国汉族副肿瘤性天疱疮(paraneolastic pemphigus,PNP)患者是否存在HLA-Ⅱ类易感基因.方法 共收入PNP患者19例作为研究对象,采用颜色标记的序列特异性寡核苷酸技术(SSOP)对其HLA-DRB1, DQB1位点进行分型,并与正常人资料进行对比,并进行统计学处理.结果 PNP患者中HLA-DQB1*0301,DRB1*08 和 DRB1*11等的基因频率高于正常人群组,但经过组间校正后,校正的Pc值＞0.05,2组间差异无统计学意义.结论 19例PNP患者中未发现HLA-Ⅱ类易感基因.     

Human leukocyte antigen class I and class II genes polymorphisms might be associated with interferon α therapy efficiency of chronic hepatitis B

Certain host genetic polymorphisms in human leukocyte antigen (HLA) genes are reported to be associated with response to interferon α (IFNα) therapy. Two hundred and eighteen IFNα treatment-na?ve chronic hepatitis B (CHB) patients were enrolled in the present study. HLA-A, B, C and DQA1, DQB1, DRB1 gene alleles were detected by polymerase chain reaction-sequencing based typing (PCR-SBT) and PCR-sequence specific primer (PCR-SSP), respectively. Frequencies of HLA-DQB1*0303 and DRB1*08 in response group were clearly lower than those in nonresponse group (P=0.019, OR=1.81, 95%CI=1.07-3.15; P=0.031, OR=2.43, 95%CI=1.02-5.98, respectively). Frequencies of haplotype *1101-*4601-*0102 (HLA-A, B, C) and haplotype *0302-*0303-*09 (HLA-DQA1, DQB1, DRB1) were clearly lower than those in nonresponse group (P=0.009, OR=4.84, 95%CI=1.29-19.48; P=0.031, OR=1.94, 95%CI=1.01-3.73, respectively). These results suggest that patients with HLA-DQB1*0303 or DRB1*08 alleles, and haplotype *1101-*4601-*0102 (HLA-A, B, C) or haplotype *0302-*0303-*09 (HLA-DQA1, DQB1, DRB1), might be less responsive to IFNα treatment.     

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。     

Helicobacter pylori, parietal cell antibodies and autoimmune gastropathy in type 1 diabetes mellitus

BACKGROUND: Fifteen to 20% of type 1 diabetic patients exhibit parietal cell antibodies (PCA), which are associated with autoimmune gastritis, hypochlorhydria, iron deficiency and pernicious anaemia. AIM: To examine whether Helicobacter pylori infection could explain the high prevalence of PCA and autoimmune gastropathy in diabetes. If so, H. pylori eradication could prevent autoimmune gastritis. METHODS: In 229 type 1 diabetics (M/F: 135/94; age: 41 +/- 12 years) PCA were measured. H. pylori infection was assessed by serology, urea breath test in all and by histology (updated Sydney system) in 88 subjects. Pentagastrin tests were performed in 42 patients. RESULTS: Sixty-nine patients were PCA-positive. H. pylori infection was present in 72 patients and was negatively associated with HLA-DQA1*0103-B1*0603 (OR=0.12, P=0.015) and positively with DQA1*0501-B1*0201 (OR=1.9, P=0.032). PCA-positivity was linked to HLA-DQA1*0501-B1*0301 (OR=3.9, P=0.017). A link between H. pylori and PCA was observed when PCA-positivity was defined as a titre > or = 1/20 (OR=2.0, P=0.03), but not if > or =1/40 was the cut-off point. PCA-positivity, but not H. pylori infection, was associated with iron deficiency anaemia (OR=2.7, P=0.008), pernicious anaemia (OR= 33.5, P < 0.0001), hypochlorhydria (OR=12.1, P=0.0008) and autoimmune gastritis (OR=12.5, P < 0.0001). CONCLUSIONS: The HLA-bound susceptibility of H. pylori and PCA differed. PCA-positivity but not ongoing H. pylori infection is associated with autoimmune gastritis. Low titres of PCA might reflect H. pylori infection rather than autoimmune gastropathy.     

用核酸序列测定法对1型糖尿病HLA-DPB1、DQB1基因分析

目的　研究山东地区汉族人 1型糖尿病与HLA -DPB1和HLA -DQB1等位基因的相关性。方法　采用基于核酸序列测定的基因分型技术对 5 2例 1型糖尿病患者及 3 8名正常对照者进行了DPB1和DQB1基因分析。结果　DPB1 2 2 0 1(P <0 .0 1)和DQB1 0 2 0 1(P <0 .0 1)、 0 3 0 3 (P <0 .0 5 )及 0 60 4 (P <0 .0 5 )等位基因频率在糖尿病患者组显著高于对照组 ,而DPB1 0 4 0 2 (P <0 .0 1)和DQB1 0 3 0 1(P <0 .0 1)等位基因在糖尿病患者组显著低于对照组。结论　DPB1 2 2 0 1和DQB1 0 2 0 1、 0 3 0 3及 0 60 4等位基因可能是山东地区汉族人 1型糖尿病的易感性等位基因 ,而DPB1 0 4 0 2和DQB1 0 3 0 1等位基因可能是山东地区汉族人 1型糖尿病的保护性等位基因     

中国人群TGFβ1基因多态性与乙型肝炎肝硬化关系的Meta分析

目的 探索转化生长因子（Transforming growth factor β1, TGFβ1）基因多态性与我国人群乙型肝炎肝硬化的关系。方法 计算机检索中国生物医学文献数据库、重庆维普中文科技期刊全文数据库,清华CNKI数据库、万方科技期刊全文数据库、Pubmed,检索时间范围为建库到2013年7月。按纳入、排除标准选择TGFβ1基因509位点、869位点基因多态性与乙型肝炎肝硬化关系的病例对照研究。应用RevMan 5.1软件对纳入的研究进行定量分析。结果 共纳入6个病例对照研究。Meta分析结果显示509位点携带T等位基因的乙型肝炎肝硬化的合并OR值为1.02,95%CI为（0.67~1.54）,CT和TT基因型者乙型肝炎肝硬化的合并OR值为0.80,95%CI为（0.36~1.78）;869位点携带C等位基因的乙型肝炎肝硬化的合并OR值为1.05,95%CI为（0.69~1.62）,TC和CC基因型者乙型肝炎肝硬化的合并OR值为0.98,95%CI为（0.48~2.00）。未发现显著发表偏倚。结论 未发现中国人群中TGFβ1 基因多态性与乙型肝炎肝硬化有联系。     

Positive and negative associations of HLA class I alleles with allopurinol-induced SCARs in Koreans

Recent investigations suggest genetic susceptibility of allopurinol-induced severe cutaneous adverse reactions (SCARs). However, the strength of association was variable according to phenotypes and ethnic backgrounds. To explore genetic markers for allopurinol-induced SCARs in Koreans, we genotyped human leukocyte antigen (HLA) class I alleles of 25 cases of allopurinol-induced SCARs (20 cases of drug-induced hypersensitivity syndrome and five cases of Stevens-Johnson syndrome/toxic epidermal necrolysis) and 57 patients tolerant to allopurinol. Frequencies of B*5801 [92.0 vs. 10.5%, P(c)=2.45×10(-11), odds ratio (OR)=97.8], Cw*0302 (92.0 vs. 12.3%, P(c)=9.39×10(-11), OR=82.1), and A*3303 (88.0 vs. 26.3%, P(c)=3.31×10(-6), OR=20.5) were significantly higher in SCARs compared with tolerant controls. In contrast, A*0201 was not found in SCARs patients despite relatively high frequency in tolerant controls (29.8%). We found strong positive association of HLA-B*5801 and negative association of HLA-A*0201 with the development of allopurinol-induced SCARs in the Korean population.     

An investigation of the catalytic activity of CYP2A13*4 with coumarin and polymorphisms of CYP2A13 in a Chinese Han population

CYP2A13 has been identified as an efficient catalyst for the metabolisms of coumarin, aflatoxin B(1) (AFB(1)), and several tobacco-specific carcinogens. The reported CYP2A13 polymorphisms with missense variations have been studied for their functional consequences, and CYP2A13*4 (R101Q) variant was found to be a null enzyme in metabolizing 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), AFB(1), and 5-methoxypsoralen. In the present study, CYP2A13*4 was expressed in Sf9 cells and evaluated for coumarin 7-hydroxylation activity. Our results demonstrated that CYP2A13*4 showed no activity in coumarin 7-hydroxylation. Furthermore, computer modeling studies were conducted to probe the mechanisms underlying the loss of catalytic activity of CYP2A13*4. The results suggested that the R101Q alteration may result in the absence of several hydrogen bonds involved in heme binding and thus lead to the loss of function in CYP2A13*4. In addition, for the first time, the distribution frequencies of all eight known CYP2A13 missense alleles were examined in a Chinese Han population. The distribution frequencies of CYP2A13*3 allele and CYP2A13*4 allele in the Chinese Han population were statistically significantly different from the reported values in Japanese. Considering that the two variants of CYP2A13 are incapable of metabolic activation of NNK and AFB(1), the susceptibility to NNK or AFB(1) exposure between the Chinese Han population and Japanese can be different.     

Phenotyping and genotyping study of thiopurine S-methyltransferase in healthy Chinese children: a comparison of Han and Yao ethnic groups

AIMS: Ethnicity is an important variable influencing drug response. Thiopurine S-methyltransferase (TPMT) plays an important role in the metabolism of thiopurine drugs. Previous population studies have identified ethnic variations in both phenotype and genotype of TPMT, but limited information is available within Chinese population that comprises at least 56 ethnic groups. The current study was conducted to compare both phenotype and genotype of TPMT in healthy Han and Yao Chinese children. METHODS: TPMT activity was measured in healthy Chinese children by a HPLC assay (n = 213, 87 Han Chinese and 126 Yao Chinese). Allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP) were used to determine the frequency of TPMT mutant alleles (TPMT*2, TPMT*3 A, TPMT*3B and TPMT*3C) in these children. RESULTS: There was no significant difference in the mean TPMT activity between Han and Yao Chinese children. A unimodal distribution of TPMT activity in Chinese children was found and the mean TPMT activity was 13.32 +/- 3.49 U ml(-1) RBC. TPMT activity was not found to differ with gender, but tended to increase with age in Yao Chinese children. TPMT*2, TPMT*3B and TPMT*3A were not detected, and only one TPMT*3C heterozygote (Han child) was identified in 213 Chinese children. Erythrocyte TPMT activity of this TPMT*3C heterozygote was 12.36 U ml(-1) RBC. The frequency of the known mutant TPMT alleles was 0.2%[1/426] in Chinese children. CONCLUSION: The frequency distribution of RBC TPMT activity was unimodal. The frequency of the known mutant TPMT alleles in Chinese Children is low and TPMT*3C appears to be the most prevalent among the tested mutant TPMT alleles in this population.