HLA-DRB1等位基因与中国北方地区汉族人2型糖尿病大血管病变的相关性研究

目的 :探讨HLA DRB1基因多态性与 2型糖尿病 (type 2diabetesmellitus,T2DM)大血管病变的关系。方法 :采用序列特异性引物聚合酶链反应技术 (polymerasechainreactionwithsequence specificprimers ,PCR SSP)检测了中国北方地区汉族人88例T2DM患者 ( 5 2例无并发症 ,36例合并大血管病变 )HLA DRB1等位基因多态性。结果 :T2DM患者至少存在 11种HLA DRB1等位基因 ,T2DM伴大血管并发症组HLA DRB1 0 3、HLA DRB1 0 90 12基因频率明显高于无并发症组 (P <0 .0 5 )。结论 :HLA DRB1基因中DRB1 0 3、DRB1 0 90 12等位基因或其连锁不平衡基因可增高T2DM发生大血管并发症的危险性     

用核酸序列测定1型糖尿病HLA-DPB1和DQB1第2外显子基因

目的 研究山东省汉族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52例1型糖尿病患者及38例正常对照进行了DPB1和DQB1基因分析。结果 DPB1＊2201（P＜0．01）和DQB1＊0201（P＜0．01）、＊0303（P＜0．05）及＊0604（P＜0．05）等位基因频率在糖尿病患者组显著高于对照组,而PB1＊0402（P＜0．01）和DQB1＊0301（P＜0．01）等位基因在糖尿病患者组显著低于对照组。结论 DPB1＊2201和DQB1＊0201、＊0303及＊0604等位基因可能是山东省汉族1型糖尿病的易感性等位基因,而DPB1＊0402和DQB1＊0301等位基因可能是山东省汉族1型糖尿病的保护性等位基因。     

HLA-DRB1等位基因与中国北方汉族多发性肌炎/皮肌炎的相关性

目的　探讨HLA DRB1等位基因与中国北方汉族多发性肌炎 (PM) 皮肌炎 (DM)的相关性。方法　采用聚合酶链反应 序列特异性引物 (PCR SSP)技术 ,检测中国北方汉族PM DM患者的HLA DRB1等位基因。结果　与 16 8例正常对照组比较 ,在 5 2例PM DM患者中HLA DRB1 0 40x和DRB1 12 0x等位基因频率明显增高 ,且差异有非常显著性 ( χ2 =2 9.80 ,RR =6 .6 1,Pc <0 .0 1;χ2 =2 2 .2 2 ,RR =5 .82 ,Pc<0 .0 1) ;DRB1 0 70x的基因频率也明显高于正常对照组的基因频率 ,且差异有显著性 ( χ2 =10 .6 8,RR =4.48,Pc<0 .0 5 )。 38例DM患者中HLA DRB1 0 40x和DRB1 12 0x等位基因频率明显增高 ,差异有非常显著性 ( χ2 =2 6 .33,Pc<0 .0 1;χ2 =2 0 .82 ,Pc<0 .0 1) ;DRB1 0 70x的基因频率也明显高于正常对照组的基因频率 ,且差异有显著性 ( χ2 =9.6 2 ,Pc<0 .0 5 )。 14例PM患者HLA DRB1 0 40x基因频率也明显增高 ,但经P值校正后无统计学意义 ( χ2 =6 .12 ,Pc>0 .0 5 )。 10例伴间质性肺炎型患者HLA DRB1 12 0x等位基因频率较正常对照组的基因频率明显增高 ,且差异有非常显著性 ( χ2 =12 .5 6 ,Pc<0 .0 1)。结论　PM DM与HLA DRB1 0 40x、 0 70x和 12 0x有显著性相关 ,为揭示PM DM的发病机制中免疫遗传学机制所起的     

HLA-DQB1等位基因与皮肌炎/多发性肌炎相关性研究

目的　探讨 HL A- DQB1等位基因与皮肌炎 /多发性肌炎 (dermatomyositis/polymyositis,DM/PM)的相关性。方法　采用聚合酶链反应 -序列特异性引物技术 ,检测了 DM/PM患者的 HL A- DQB1等位基因。结果　与 16 0名正常对照比较 ,在 5 2例 DM/PM患者中 HL A- DQB1* 0 4 0 1等位基因频率明显增高 ,且差异有显著性 (RR=3.5 6 ,P=1.79× 10 - 3,Pc<0 .0 5 ) ;HL A- DQB1* 0 30 3的检出频率在 DM/PM患者组中有降低倾向 ,但两组差异无显著性。结论　DM/PM与 HL A- DQB1* 0 4 0 1基因有显著性相关 ,为揭示 DM/PM的发病中免疫遗传学机理所起的作用提供了重要线索和依据。     

谷氨酸脱羧酶抗体、胰岛细胞自身抗体联合检测早期诊断成人迟发性自身免疫性糖尿病

目的 探讨谷氨酸脱羧酶抗体(GADA)与胰岛细胞自身抗体(ICA)的联合检测,早期诊断成人迟发性自身免疫性糖尿病.方法 采用ELISA法对358例糖尿病患者的血清进行GADA与ICA的联合检测.将患者分为两组,A组为胰岛素依赖性(1型)糖尿病患者组,B组为2型糖尿病患者组,比较两组患者的检测结果.结果 1型糖尿病患者组GADA阳性率为52.34%,ICA阳性率为30.84%(P<0.005)明显高于2型糖尿病组(GADA阳性率为26.77%,ICA阳性率为13.39%).GADA与ICA联合检测,则1型糖尿病组的阳性率为69.56%,2型糖尿病组为24.62%.结论 GADA在1型糖尿病患者血清中有较高的阳性率,可作为1型糖尿病的免疫诊断指标,GADA与ICA的联合检测可提高1型糖尿病的检出率.对2型糖尿病而言,GADA、ICA各有一定的阳性率,其联合检测,可提高成人隐匿性自身免疫性糖尿病(LADA)的及早筛出与治疗,并为临床及早应用胰岛素治疗,以保护残存的胰岛β细胞功能提供了依据.     

儿童1型糖尿病外周血Foxp3+调节T细胞和细胞因子变化及相关分析

目的 探讨初发儿童1型糖尿病(T1DM)外周血CD4+ CD25+ Foxp3+调节性T细胞(Foxp3+ Treg)及相关细胞因子的表达水平与自身抗体和胰岛细胞功能的关系.方法 45例儿童T1DM(T1DM组)患儿根据有无并发酮症酸中毒(DKA)和是否出现自身抗体分为DKA组、非DKA组、自身抗体阳性组、自身抗体阴性组,30例正常健康儿童作为对照组.采用流式细胞术检测外周血Foxp3+ Treg百分率,ELISA法检测血清IL-18、IL-10的表达水平,免疫印迹法(IB)检测血清谷氨酸脱羧酶抗体(GADA)、胰岛素瘤相关蛋白2自身抗体(IA-2A)和胰岛素自身抗体(IAA);电化学发光法(ECLIA)检测血清空腹C肽(FC-P)水平.结果 T1DM组外周血Foxp3+ Treg百分率、血清IL-10水平和FCP含量明显低于正常对照组(P＜0.01),而血清IL-18水平则显著高于正常对照组(P＜0.01);DKA组、自身抗体阳性组外周血Foxp3+ Treg百分率和FCP含量明显低于非DKA组和自身抗体阴性组(P＜0.01),血清IL-18水平则显著高于非DKA组和自身抗体阴性组(P＜0.01),IL-10在T1 DM各组间差异无统计学意义.T1DM组患者GADA、IA-2A和IAA的检出率明显高于正常对照组(P＜0.01,P＜0.05).相关分析显示,Foxp3+Treg百分率与IL-10、FC-P水平呈正相关,而与IL-18水平及自身抗体呈负相关;IL-18与自身抗体呈正相关,而与IL-10、FC-P呈负相关;IL-10水平与FC-P含量及胰岛自身抗体无明显相关性.结论 初发儿童1型糖尿病外周血Foxp3+ Treg百分率减低及相关细胞因子的表达水平失衡可能参与了儿童T1DM的发生和发展,并与自身抗体和胰岛细胞功能相关.     

CDKAL1基因rs4712523多态性与内蒙古地区汉族人群2型糖尿病相关

目的 研究内蒙古地区汉族人群CDKAL1基因rs4712523单核苷酸多态性(SNP)的等位基因和基因型频率分布与2型糖尿病(T2DM)的相关性.方法 采用等位基因特异性聚合酶链式反应(AS-PCR),对382例内蒙古地区汉族人(其中T2DM组192例,对照组190例)rs4712523进行基因分型.结果 T2DM组中rs4712523的G等位基因频率和GG基因型频率分别为47.4％和6.3％,均显著高于对照组的35.3％和3.2％(P＜0.05).G等位基因携带者患T2DM的风险是A等位基因的1.654倍(OR=1.654,95％ CI=1.237-2.212).结论 CDKAL1基因rs4712523多态性位点的G等位基因可能是内蒙古地区汉族人T2 DM的易感基因之一.     

妊娠糖尿病患者血清TGF-β1基因多态性预测产后T2DM发病风险相关性研究

目的 探究妊娠糖尿病(GDM)患者血清转化生长因子-β₁(TGF-β₁)基因多态性在预测产后2型糖尿病(T2DM)发病风险的价值。方法 选取保定市妇幼保健院1352例GDM患者,进行前瞻性研究,根据产后2年内是否发生T2DM分为T2DM组、无T2DM组。比较两组基线资料、TGF-β₁基因-509C/T和+869T/C位点多态性,分析TGF-β₁基因多态性与产后T2DM发病风险相关性。结果 完成随访的1346例GDM患者产后2年内T2DM发生率为6.17%(83/1346);T2DM组糖尿病家族史占比、产后口服葡萄糖耐量试验(OGTT)2 h、母乳喂养占比、产后胰岛素抵抗指数(HOMA-IR)均高于无T2DM组;基因分型检测结果显示,-509C/T位点基因型为CC、CT、TT,+869T/C位点基因型为TT、TC、CC,均存在多态性;产后OGTT 2 h、母乳喂养、产后HOMA-IR、+869T/C基因型TC、CC与C等位基因均是GDM患者产后T2DM发病的影响因素。结论 GDM患者产后T2DM发病与...     

HLA-DRB1、DQB1基因与汉族人群寻常型天疱疮的相关性研究

目的　探讨 HL A- DRB1、DQB1位点基因在汉族人群寻常型天疱疮易感性中的作用。方法用序列特异性引物 -聚合酶链反应方法 ,对 6 1例寻常型天疱疮 (pemphigus vulgaris,PV)患者和 5 7名正常对照进行了 HL A- DRB1、DQB1等位基因的分型 ,并分析了 DRB1、DQB1基因在两组中的分布。结果　与正常对照组比较 ,PV组 DR4、DRB1* 14 (* 14 0 1、* 14 0 4、* 14 0 5 )基因频率明显增高 (Pc分别 <0 .0 5及P<0 .0 1) ,差异有显著性 ;PV组 DQB1* 0 5 0 3、DQB1* 0 30 2基因频率明显增高 (Pc均 <0 .0 5 ) ,差异有显著性。对 DR4阳性样本的组内基因亚型分型结果发现 ,PV组中 DRB1* 0 4 0 3、DRB1* 0 4 0 6频率显著增高(Pc<0 .0 5 ) ,差异有显著性。 PV患者组单倍型 HL A- DRB1* 0 4 ,DQB1* 0 30 2和 HL A- DRB1* 14 ,DQB1* 0 5 0 3频率明显增高 (P<0 .0 5 )。结论　HL A- DRB1* 0 4 ,DQB1* 0 30 2和 HL A- DRB1* 14 ,DQB1* 0 5 0 3可能是汉族人 PV推测的易感单倍型。     

2型糖尿病性骨质疏松与血清胰岛素样生长因子-1、骨碱性磷酸酶、1,25羟维生素D3水平的关系

目的 研究2型糖尿病性骨质疏松与血清胰岛素样生长因子-1 (IGF-I)、骨碱性磷酸酶(BAP)、1,25羟维生素D3[1,25(OH)D3]水平的关系.方法 选择2013年1月至2017年12月于我院就诊的60例2型糖尿病伴骨质疏松患者(T2DM+OP组),另选取我院同期就诊的60例2型糖尿病不伴有骨质疏松症患者(T2DM组),再选取同期我院体检的60例健康者(对照组).分析2型糖尿病性骨质疏松与IGF-1、BAP、1,25(OH) D3水平的关系.结果 与对照组比较,T2DM+ OP组和T2DM组IGF-1、l,25(OH) D3和骨密度(BMD)水平均明显降低,且T2DM+ OP组降低程度比T2DM组大,差异有统计学意义(P＜0.05);与对照组比较,T2DM+ OP组和T2DM组BAP水平均明显升高,且T2DM+ OP组升高程度比T2DM组大,差异有统计学意义(P＜0.05);T2DM+ OP组患者BMD水平与IGF-1(γ=0.823,P=0.022)、1,25(OH)D3(γ =0.751,P=0.033)呈正相关,与BAP(γ=-0.721,P=0.023)呈负相关;多元逐步回归分析结果显示,IGF-1(P =0.035,OR =20.599)和1,25 (OH) D3(P=0.016,OR=30.188)是2型糖尿病骨质疏松的保护因素.而BAP(P=0.034,OR=18.362)为危险因素.结论 IGF-1、BAP、1,25(OH) D3水平变化与糖尿病性骨质疏松的发生密切相关,低水平IGF-1和1,25 (OH) D3,高水平BAP是2型糖屎病患者并发骨质疏松的危险因素.     

Polymorphisms of HLA Class II Predispose Children and Adolescents with Type 1 Diabetes Mellitus to Autoimmune Thyroid Disease

To determine the prevalence of autoimmune thyroid disease (AITD) in children and adolescents with type 1 diabetes mellitus (DM), and assess whether the development of AITD is correlated with specific DQ-A and DQ-B loci of the HLA class II antigens, we analyzed thyroid function using anti-thyroid antibodies and HLA-DQ-A and -DQ-B polymorphisms in 69 patients with type 1 DM, in 75 normal healthy controls, and in 21 patients with AITD but without type 1 DM. Eighteen patients (26%) in the diabetic patients had AITD. In the diabetic patients, DQA1*0301 and DQB1*0302 occurred more frequently than in controls [DQA1*0301: OR=1.939, 95% CI=1.210–3.109 (P=0.008, P^c (corrected P) <0.05); DQB1*0302: OR=2.558, 95% CI=1.354–4.832 (P=0.005, P_c>0.05)]. Compared with controls, non-diabetic subjects with AITD showed higher frequency of DQA1*0301 (P_c<0.05) and DQB1*0601 (P_c>0.05), but these alleles were not contributing factors in the development of AITD in diabetic patients. In diabetic patients, DQB1*0201, known as susceptible allele of type 1 DM was not a contributing factor in the development of AITD in diabetic patients. Unlike DQB1*0201, DQB1*0401 was more frequently found in diabetic patients with AITD than in controls [OR=4.053, 95% CI=1.607–10.221 (P=0.0017, P_c<0.05)] or than in non-diabetic AITD patients [OR=15.769, 95% CI=1.905–130.530(P=0.002, P_c<0.05)]. In non-diabetic subjects, DQB1*0401 did not provide susceptibility for AITD.

Our results suggest that HLA DQB1*0401 is a predisposing genetic marker for the development of AITD in patients with type 1 DM in Korea.     

Polymorphisms of HLA class II predispose children and adolescents with type 1 diabetes mellitus to autoimmune thyroid disease

To determine the prevalence of autoimmune thyroid disease (AITD) in children and adolescents with type 1 diabetes mellitus (DM), and assess whether the development of AITD is correlated with specific DQ-A and DQ-B loci of the HLA class II antigens, we analyzed thyroid function using anti-thyroid antibodies and HLA-DQ-A and -DQ-B polymorphisms in 69 patients with type 1 DM, in 75 normal healthy controls, and in 21 patients with AITD but without type 1 DM. Eighteen patients (26%) in the diabetic patients had AITD. In the diabetic patients, DQA1*0301 and DQB1*0302 occurred more frequently than in controls [DQA1*0301: OR = 1.939, 95% CI = 1.210-3.109 (P = 0.008, P(c) (corrected P) < 0.05); DQB1*0302: OR = 2.558, 95% CI = 1.354-4.832 (P = 0.005, P(c), > 0.05)]. Compared with controls, non-diabetic subjects with AITD showed higher frequency of DQA1*0301 (P(c), < 0.05) and DQB1*0601 (P(c) > 0.05), but these alleles were not contributing factors in the development of AITD in diabetic patients. In diabetic patients, DQB1*0201, known as susceptible allele of type 1 DM was not a contributing factor in the development of AITD in diabetic patients. Unlike DQB1*0201, DQB1*0401 was more frequently found in diabetic patients with AITD than in controls [OR = 4.053, 95% CI = 1.607-10.221 (P = 0.0017, P(c) < 0.05)] or than in non-diabetic AITD patients [OR = 15.769, 95% CI = 1.905-130.530(P = 0.002, P(c) < 0.05)]. In non-diabetic subjects, DQB1*0401 did not provide susceptibility for AITD. Our results suggest that HLA DQB1*0401 is a predisposing genetic marker for the development of AITD in patients with type 1 DM in Korea.     

Islet autoantibodies are associated with HLA-DQ genotypes in Han Chinese patients with type 1 diabetes and their relatives

The objective of this study was to explore the relationship between islet autoantibodies of glutamic acid decarboxylase (GADA), islet antigen-2A (IA-2A), insulin autoantibody (IAA), and human leukocyte antigen (HLA)-DQ genotypes in type 1 diabetes (T1D) patients and their first-degree relatives (FDRs). Cross-sectional and case-control study. Four hundred and ninety-five T1D patients, 419 FDRs, and 376 control subjects in Han Chinese populations were recruited and tested for GADA and IA-2A, while 71 cases, all FDRs and 300 controls were tested for IAA. The 338 T1D patients (including 187 antibody-positive and 151 antibody-negative patients), 173 FDRs and 278 controls were genotyped for HLA-DQ with polymerase chain reaction sequencing-based method. Compared with the control, the frequency of DQA1*03-DQB1*0303, DQA1*05-DQB1*0201, and DQA1*03-DQB1*0401 haplotypes was higher (P < 0.05-0.01) but DQA1*0102-DQB1*0602 haplotype was lower (P < 0.01) in T1D patients. DQA1*03 allele was less in the FDRs than in their probands (P < 0.05). GADA was more prevalent in T1D patients carrying DQA1*05-DQB1*0201 or DQA1*03-DQB1*0401 haplotype (55.8% vs 41.0%, 65.5% vs 40.3%, P < 0.05-0.01), whereas IA-2A presented more in the patients carrying DQA1*03-DQB1*0303 haplotype (27.0% vs 7.9%, P < 0.05-0.01), both GADA and IA-2A showed frequently in the patients with DQA1*03-DQB1*0303/DQA1*05-DQB1*0201 haplotypes (34.5% vs 9.7%, P < 0.01). GADA positivity was lower in the patients with DQA1*0102-DQB1*0602 haplotype (16.7% vs 45.9%, P < 0.05). The frequency of IAA was not different between patients with and without susceptible DQ haplotypes (P > 0.05). GADA, IA-2A or IAA presented frequently in FDRs with DQA1*03-DQB1*0303 haplotype. The findings in the study indicate that some of specific HLA-DQA1/-DQB1 genotypes and haplotypes not only confer susceptibility to T1D but also are associated with the presence of the islet autoantibodies in the Han Chinese population.     

江浙沪地区HLA-DQB1基因对重症肌无力的遗传易感性研究

探讨中国汉人ＭＧ易感性与ＨＬＡ－ＤＱＢ１基因多态性的相关。方法：运用ＰＣＲ－ＲＦＬＰ法进行ＨＬＡ－ＤＱＢ１基因分型。结果：ＭＧ病例组与对照组比较都有ＤＱＢ＊０３０３频率的明显增高,ＤＱＢ＊０６０１和ＤＱＢ１＊０．６０２频率的明显降低,差异都有显著性。结论：ＤＱＢ１＊０３０３参与中国汉人ＭＧ的易感性,而ＤＱＢ１＊０６０１和ＤＱＢ１＊０６０２是保护基因。     

The HLA-DRB, -DQB polymorphism and anti-insulin antibody response in Slovenian patients with type 1 diabetes.

A combination of specific HLA class II antigens and the presence of type 1 diabetes (T1D)-related antibodies has a high positive predictive value for T1D but low sensitivity. The aim of the present study was to determine the frequencies of HLA-DRB-DQB deduced haplotypes associated with susceptibility and protection in Slovenian patients with established T1D, to evaluate the relationship between the HLA-DRB1-QBP-DQB1 haplotypes and the presence of insulin autoantibodies (IAA) and glutamic acid decarboxylase antibodies (GADA), and to access the possible impact of polymorphic QBP promoters on this relationship. A cohort of 135 patients with T1D (age 17.5 +/- 7.0 years, duration of T1D 9.14 +/- 6.3 years) was investigated. HLA-DRB1 and DQB1 alleles were typed using the polymerase chain reaction (PCR)-reverse line blot method. QBP promoter region alleles were determined using PCR-sequence-specific oligonucleotide hybridization (SSO) and PCR-sequence-specific primers (SSP). IAA and GADA antibodies were determined by enzyme-linked immunosorbent assay (ELISA). The chi-square test with Yates' correction was used for statistical analysis. Deduced haplotypes DRB1*0301-DQB1*0201 (P = 0.0001, OR = 3.4), DRB1*0401-DQB1*0302 (P = 0.0001, OR = 29.8), and DRB1*0402-DQB1*0302 (P = 0.008, OR = 4.7) were significantly more common, and DRB1*1501-DQB1*0602 (P = 0.0001, OR = 0.03) significantly less common in the investigated cohort than in a Slovenian control group. The highest risk and the strongest protective HLA-DR-DQ haplotypes found in Slovenian patients with T1D did not differ from those found in other Caucasian populations. While the DRB1*0301-QBP2.1-DQB1*0201 haplotype, where QBP2.1 did not help to further distinguish DQB1*0201-possessing haplotypes in IAA-positive and IAA-negative patients, was strongly associated with the presence of IAA, the DRB1*0101-QBP5.12-DQB1*0501 haplotype, although not protective compared to the control population, was associated with an absence of IAA in the investigated cohort. It is suggested that there may be a combined influence of the QBP5.12 promoter and the DQB1*0501 functional molecule on reduced IAA production.     

Human leukocyte antigen-DRB1*1501 and DQB1*0602 alleles are cervical cancer protective factors among Uighur and Han people in Xinjiang,China

Human papillomavirus (HPV) infection is a major risk factor for cervical cancer. However, only some high risk human papillomavirus (HR-HPV)-infected women progress to cervical cancer, host immunogenetic factors human leukocyte antigen (HLA) may account for viral antigens presenting individually or together in the progression to cervical cancer. This study examined the association between the development of invasive cervical cancer (ICC) and the determinant factors including HLA-DRB1*1501 and DQB1*0602, HR-HPV infection among Chinese Uighur and Han populations. Blood samples, cervical swabs and biopsies were obtained from 287 patients with ICC (192 Uighurs and 95 Hans) and 312 healthy controls (218 Uighurs and 94 Hans). HPV DNA was detected by PCR and HLA-DRB1*1501 and DQB1*0602 alleles were performed using PCR-SSP method. HPV16 infection rates was significantly higher among Uighur and Han with ICC as compared to healthy controls (OR = 58.317; 95% CI: 39.663-85.744; OR = 33.778; 95% CI: 12.581-90.691; P < 0.05 for all). HLA-DRB1*1501 (OR = 0.305; 95% CI: 0.115-0.813; P < 0.05) and HLA-DRB1*1501-DQB1*0602 haplotype frequencies (OR = 0.274; 95% CI: 0.086-0.874; P < 0.05) were significantly reduced in Han ICC. The HLA-DQB1*0602 frequency significantly decreased among Uighur women with ICC (OR = 0.482; 95% CI: 0.325-0.716; P < 0.05). Similar tendencies were observed for DQB1*0602 with HPV16-positive ICC (OR = 0.550; 95% CI: 0.362-0.837; P < 0.05). This study suggests that HLA-DRB1*1501 and DQB1*0602 alleles may influence the immune response to HPV16 infection and decrease the risk of ICC among Uighurs and Hans in Xinjiang, China.     

云南汉族系统性红斑狼疮的易感及抵抗单体型研究

目的：探讨云南汉族系统性红斑狼疮（SLE）在HLA－DRB1、DQA1、DQB1等座位的易感抵抗单体型,方法：采用多聚酶链反应－序列特异性引物（PCR－SSP）技术对63例动态汉族SLE患者及54名同民族健康对照进行DRB1、DQA1、DQB1基因分型。结果：与正常对照组比较,SLE病人中有5个单体型频率显著升高;11个单体型频率在病例组中明显降低。结论：云南汉族SLE的易感单体型为DQA1^*0102-DQB1^*0601,DR15-DQA1^*0102-DQB1^*0601,DR15-DQA1^*0102-DQB1^*0602,DR15-DQA1^*0101-DQB1^*0601,DR15-DQA1^*0103-DQB1^*0601;其余均为低抗单体型。     

家族性重症肌无力与HLA-DQB1等位基因多态性的相关性

目的探讨中国北方地区家族性重症肌无力（myasthenia gravis，MG）与HLA-DQB1等位基因多态性的相互关系。方法应用聚合酶链反应．序列特异性引物方法对中国北方地区15例家族性MG、49例散发性MG和51名健康对照组的HLA-DQB1基因多态性进行分析。结果在家族性MG中DQB1＊0501等位基因频率明显高于散发MG（P〈0．05，OR：3．08）和对照（P=0．001，OR=4．439），尤其是眼型患者更加显著有统计学意义（P〈0．01，OR=7．67）。结论DQB1＊0501等位基因是家族性MG尤其是眼型患者的易感基因；遗传因素与重症肌无力发生密切相关。家族性MG有其独特的临床特点。     

The HLA‐DRB, ‐DQB polymorphism and anti‐insulin antibody response in Slovenian patients with type 1 diabetes

A combination of specific HLA class II antigens and the presence of type 1 diabetes (T1D)‐related antibodies has a high positive predictive value for T1D but low sensitivity. The aim of the present study was to determine the frequencies of HLA‐DRB‐DQB deduced haplotypes associated with susceptibility and protection in Slovenian patients with established T1D, to evaluate the relationship between the HLA‐DRB1‐QBP‐DQB1 haplotypes and the presence of insulin autoantibodies (IAA) and glutamic acid decarboxylase antibodies (GADA), and to access the possible impact of polymorphic QBP promoters on this relationship. A cohort of 135 patients with T1D (age 17.5 ± 7.0 years, duration of T1D 9.14 ± 6.3 years) was investigated. HLA‐DRB1 and DQB1 alleles were typed using the polymerase chain reaction (PCR)–reverse line blot method. QBP promoter region alleles were determined using PCR–sequence‐specific oligonucleotide hybridization (SSO) and PCR–sequence‐specific primers (SSP). IAA and GADA antibodies were determined by enzyme‐linked immunosorbent assay (ELISA). The chi‐square test with Yates’ correction was used for statistical analysis. Deduced haplotypes DRB1*0301‐DQB1*0201 (P = 0.0001, OR = 3.4), DRB1*0401‐DQB1*0302 (P = 0.0001, OR = 29.8), and DRB1*0402‐DQB1*0302 (P = 0.008, OR = 4.7) were significantly more common, and DRB1*1501‐DQB1*0602 (P = 0.0001, OR = 0.03) significantly less common in the investigated cohort than in a Slovenian control group. The highest risk and the strongest protective HLA‐DR‐DQ haplotypes found in Slovenian patients with T1D did not differ from those found in other Caucasian populations. While the DRB1*0301‐QBP2.1‐DQB1*0201 haplotype, where QBP2.1 did not help to further distinguish DQB1*0201‐possessing haplotypes in IAA‐positive and IAA‐negative patients, was strongly associated with the presence of IAA, the DRB1*0101‐QBP5.12‐DQB1*0501 haplotype, although not protective compared to the control population, was associated with an absence of IAA in the investigated cohort. It is suggested that there may be a combined influence of the QBP5.12 promoter and the DQB1*0501 functional molecule on reduced IAA production.     

Association of HLA-DR and -DQ genes with narcolepsy in Koreans: comparison with two control groups, randomly selected subjects and DRB1*1501-DQB1*0602--positive subjects

The purpose of this study was to investigate the association of human leukocyte antigen (HLA) class II alleles with narcolepsy-cataplexy susceptibility in Koreans. The distribution of HLA-DRB1 and -DQB1 alleles and presence or absence of DRB3/4/5 alleles were examined in 60 narcoleptic patients with clear-cut cataplexy, and the results were compared with two groups of healthy controls: 200 randomly selected controls and 144 DRB1*1501-DQB1*0602 positive controls. All of the narcoleptic patients were DRB1*1501 and DQB1*0602 positive, and their frequencies were significantly higher in patients than in random controls (100% vs 17.0%, p(c) = 2.3 x 10(-30), OR = 583.96; 100% vs 16.5%, p(c) = 3.9 x 10(-31), OR = 605.00). The HLA association in Koreans was as tight as that reported in Japanese. Several DRB1 (*0101, *0405, *0901) and DQB1 alleles (*0303, *0401, *0501, *0601, *0604) were found to have weak protective effects against narcolepsy. DRB4 showed strong protective effect, and this was also significant when compared with DRB1*1501-DQB1*0602 positive controls (18.3% vs 44.4%, p(c) = 0.001, OR = 0.28). DRB3 (OR = 1.86) and DQB1*0301 (OR = 2.45) were found to have weak predisposing effect, when compared with DRB1*1501-DQB1*0602 positive controls. The protective effect of DRB4 has to be further studied in other populations.