广西汉族妊娠期糖尿病与HLA-DQA1基因相关性研究

目的探讨广西地区汉族妊娠期糖尿病（GDM）与HIA-DQA1等位基因的相关性。方法采用聚合酶链反应-序列特异性引物法检测50例GDM孕妇和50例正常孕妇的HLA．DQAI基因型。结果GDM孕妇与正常孕妇相比较,HLA-DQA1＊0501基因频率明显升高,差异有显著性（P=0．006）。HLA—DQA1＊0101、0104、0201、0601等位基因频率在GDM孕妇中有增高趋势,但差异没有显著性（P均〉0．05）。GDM孕妇中HLA—DQA1＊0102、0103、0301、0302和0401基因频率有降低趋势,差异亦无著性（P均〉0．05）。结论广西地区汉族GDM与HLA—DQA1基因相关,HLA—DQA1％0501基因可能为广西地区汉族GDM的易感基因,未发现与HIA—DQA1相关的GDM保护基因。     

儿童期1型糖尿病与HLA—DQB1等位基因的关联研究

目的 研究哈尔滨市儿童期1型糖尿病与HLA－DQB1等位基因的关联关系。方法 选取49例0－14岁发病的1型糖尿病患者和75名健康儿童对照,运用PCR－SSOP技术对部分HLA－DQB1等位基因进行了分型。结果 发现在HLA－DQB1位点上,病例组的DQB1＊0201、＊0303、＊0401频率显著高于对照组,而DQB1＊0301、DQB1＊0501和＊0601频率是显著下降的。结论 研究提示：HLA－DQB1位点的＊0201、＊0303和＊0401对儿童期1型糖尿病具有强易感性,而DQB1＊0301、＊0501和＊0601具有保护性。但未证实DQB1＊0602具有保护作用。     

蒙族和汉族人群HLA-DQA1基因多态性与支气管哮喘的关系

目的 研究蒙族和汉族人群HLA-DQA1基因多态性与支气管哮喘的关系.方法 采用引物序列特异性聚合酶链反应（PCR-SSP）方法对祖籍三代居住在内蒙古地区无血缘关系、异族通婚史,无高血压、糖尿病、免疫系统疾病、炎性肠病等与HLA相关病史及家族史的汉族哮喘患者32例、蒙古族哮喘患者34例进行HLA-DQA1等位基因频率的检测,并分别与符合以上标准、长期居住在内蒙古地区的33例健康汉族和30例健康蒙古族对照者进行比较分析.结果 汉族哮喘组DQA1 ＊ 0501、0301、0302、0201等位基因频率分别为35.93%、46.88%、43.75%和40.63%,较汉族健康组（19.70%、36.37%、6.06%和6.06%）明显增高（P〈0.05）;蒙古族哮喘患者DQA1 ＊ 0501、0302、0104等位基因频率分别为22.06%、36.77%和16.18%,较健康蒙古族（5.00%,5.00%和5.00%）明显增高（P〈0.05）;健康汉族人群DQA1 ＊ 0501等位基因频率高于健康蒙古族人群（P〈0.05）;DQA1 ＊ 0201和0301等位基因却在汉族哮喘患者中明显增高,在健康蒙古族与蒙古族患者之间分布无差异.结论 DQA1 ＊ 0501、0302是汉族和蒙古族哮喘患者共同的易感基因;DQA1＊ 0201、0301等位基因是汉族哮喘患者发病特有的易感基因;DQA1 ＊ 0501等位基因是蒙古族人群中的一个少见基因;DQA1 ＊ 0104等位基因是蒙古族哮喘患者发病的易感基因;该研究进一步证明HLA-DQ基因的种族差异性和在哮喘发病方面的多态性.     

中国HLA-DQ基因多态性与重症肌无力相关性的系统评价

目的运用循证医学系统评价我国人类白细胞抗原(HLA)-DQ基因多态性与重症肌无力(MG)之间的相关性。方法计算机检索Pubmed、Ovid、Embase、CBM、CNKI、万方数据库、VIP等,查找2016年6月前发表的关于我国HLA-DQ基因多态性与MG之间关联的文献。按Cochrane系统评价的方法,由两名研究者独立进行质量评价和资料提取,采用RevMan5.2软件进行Meta分析。结果共纳入15篇文献,样本量为2 364例,其中病例组(MG组)1 073例,健康对照组1 291例。Meta分析结果示:增加重症肌无力风险的HLA-DQ等位基因有:HLA-DQA1*0102[OR=1.43,95%CI(1.14,1.81)]、HLA-DQB1*0301[OR=1.62,95%CI(1.29,2.03)]、HLA-DQB1*0501[OR=1.53,95%CI(1.16,2.01)];降低重症肌无力风险的HLA-DQ等位基因有:HLA-DQA1*0201[OR=0.61,95%CI(0.45,0.83)]、HLA-DQB1*0601[OR=0.55,95%CI(0.44,0.69)]、HLA-DQB1*0602[OR=0.49,95%CI(0.38,0.62)]。结论中国人群,重症肌无力的易感基因HLA-DQA1*0102、HLA-DQB1*0301、HLA-DQB1*0501,而HLA-DQA1*0201、HLA-DQB1*0601、HLA-DQB1*0602为重症肌无力的保护基因。     

中国北方汉族人群人类白细胞抗原-DQA1及-DQB1基因第二外显子多态性与扩张型心肌病遗传易感性研究

目的:研究人类白细胞抗原(human leukocyte antigen,HLA)-DQA1,HLA-DQB1基因第二外显子多态性与我国北方汉族人群特发性扩张型心肌病(idiopathic dilated cardiomyopathy,IDC)的相关性及连锁关系。探讨特发性扩张型心肌病发病的免疫学机制及遗传易感性。 方法:采用聚合酶链反应-序列特异性引物法对68例特发性扩张型心肌病患者和15例特发性扩张型心肌病家系成员(n=83,IDC组)及100名健康个体(正常对照组)行HLA-DQA1,HLA-DQB1第二外显子基因分型;IDC组均接受超声心动图检测射血分数并据此分层:射血分数0.35-0.5者(n=21),射血分数0.15-0.34者(n=36)及<0.15者(n=26)。 结果:HLA-DQA1*0501基因和HLA-DQB1*0303基因频率在IDC组明显高于正常对照组。且该趋势随射血分数降低而愈趋明显,表现为HLA-DQA1*0501及HLA-DQB1*0303基因型在射血分数<0.15(阳性基因数分别为41和21)的特发性扩张型心肌病患者中分布高于射血分数≥0.15(阳性基因数分别为27和15)者。IDC组HLA-DQA1*0201基因频率和HLA-DQB1*0502、*0504基因频率明显低于正常对照组(P<0.05)。HLA-DQA1,HLA-DQB1基因与特发性扩张型心肌病家系连锁分析Lod值<1。 结论:HLA-DQA1*0501和HLA-DQB1*0303与我国北方汉族特发性扩张型心肌病患者遗传易感性相关;而HLA-DQA1*     

湖北食管癌HLA-DQB1的基因多态性

目的从基因水平探讨湖北地区汉族人食管癌HLA-DQB1等位基因的遗传易感性.方法运用序列特异性引物聚合酶链反应技术,检测无亲缘关系湖北汉族健康人136例、食管癌组42例患者的HLA-DQB1等位基因.SAS system统计软件数据处理.结果湖北汉族人食管癌患者与正常人比较,HLA-DQB1*0301基因频率显著增高(0.2976vs0.1875),P=0.046,OR=1.835,病因分数=0.1354);两组间HLA-DQB1其余各等位基因分布频率的比较,HLA-DQB1*0201(0.0833 vs 0.1016),*0301(0.2976 vs 0.1875),*0302(0.0595 vs 0859),*0303(0.2381 vs 0.1875),*0304(0.0000 vs 0.0039),*0401(0.0714 vs 0.0469),*0402(0.0119 vs 0.0156),*0501(0.0357 vs 0.0703),*0502(0.0595 vs 0.0664),*0503(0.0119 vs 0.0195),*0504(0.0000 vs 0.0039),*0601(0.0595 vs 0.0781),*0602(0.0476 vs 0.0742),*0603(0.0000 vs 0.0078),*0604(0.0238 vs 0.0508),差异均无显著性.结论 HLA-DQB1*0301等位基因与湖北汉族人食管癌正关联,为其易感基因.林军,邓长生,孙洁,周燕,熊平,汪亚平.湖北食管癌HLA-DQB1的基因多态性.世界华人消化杂志,2000;8(9):965-968     

1型糖尿病与HLA—DQB1基因及自身抗体相关性研究

采用基因分型技术,确定32例1型糖尿病患及23例正常对照的HLA-DQB1等位基因。用酶联免疫吸附法测定血清中谷氨酸脱羧酶抗体（GADA）、胰岛细胞抗体（ICA）及胰岛自身抗体（IAA）。结果在1型患中,DQB1*0201、*0303、*0604等位基因频率显高于对照（P＜0.05),DQB1*0301则低于对照（P＜0.05),其余DQB1等无显性差异。等位基因为DQB1*0201的患中GADA阳性率显高于阴性率。结论：在中国汉族人群中,DQB1*0201、*0303、*0604是1型糖尿病易感性等位基因,DQB1*0301是1型糖尿病保护性等位基因。DQB1*0201可能对GADA的产生起允许作用。     

扩张型心肌病心力衰竭患者HLA-DQA1及-DQB1基因多态性研究

目的研究人类白细胞抗原(HLA)-DQA1,-DQB1基因多态性对扩张型心肌病(IDC)心力衰竭患者心功能的影响.探讨IDC发病的免疫学机制及遗传易感性.方法采用PCR-SSP方法对68例无血缘关系、长期居住在中国北方地区的汉族IDC患者和4个IDC家系成员及100名健康者进行HLA-DQA1,-DQB1基因分型;IDC组所有研究对象均接受超声心动图检测心脏射血分数(EF值)并据此进行分层EF值35%～50%者为亚组1,EF值15%～35%者为亚组2,＜15%者为亚组3.结果HLA-DQA1*0501基因和HLA-DQB1*0303基因频率在IDC组(分别为0.3889和0.1806)明显高于正常对照组(分别为0.0900和0.0364),OR值分别为5.20(95%CI3.60-8.50)和4.85(95%CI2.56-9.39).且该趋势随射血分数降低而愈趋明显,表现为HLA-DQA1*0501及HLA-DQB1*0303基因型在EF值＜15%的IDC患者中分布高于EF值≥15%者.相反,IDC组HLA-DQAl*0201基因(0.2000比0.0139)和HLA-DQB1*0502(0.0727比0.0139)、*0504(0.1091比0.0417)基因明显低于正常对照组(P＜0.05).IDC组中HLA-DQAI*0501基因型患者与IDC组中其他基因患者相比,临床心力衰竭症状较重,EF值明显降低(P＜0.01).HLA-DQB1各基因型间EF值未见统计学差异.HLA-DQA1,-DQB1基因与IDC家系连锁分析LOD值＜1.结论HLA-DQA1*0501和HLA-DQB1*0303与我国北方汉族IDC患者遗传易感性相关;而HLA-DQA1*0201和-DQB*0502、*0504则是IDC的保护基因.DQB1基因外显子第57位的丝氨酸对IDC具有保护性,其缺失或取代有可能造成IDC易患倾向.HLA-DQ基因多态性可作为IDC的遗传标记.     

HLA-DQ等位基因与哮喘相关性研究

目的探讨在中国汉族哮喘家系中,HLA-DQ基因与哮喘的相关性。方法对98例哮喘家系成员,用PCR-序列特异性引物(PCR-SSP)技术对HLA-DQA1和B1进行基因分型,并与正常对照进行比较。结果发现DQA1*0101和DQA1*0601等位基因频率在哮喘患者组(40.0%,45.0%)较正常对照组(16.4%,13.4%)显著升高(χ2=6.1860,P<0.05,RR=3.39;χ2=11.6090,P<0.01,RR=5.27);DQB1*0303和DQB1*0601等位基因频率在哮喘患者组(55.0%,47.5%)较正常对照组(13.7%,13.7%)显著升高(χ2=15.7400,P<0.01,RR=7.68;χ2=10.9300,P<0.01,RR=5.69)。同时发现HLA-DQB1*0201等位基因频率在对屋尘螨抗原特异性IgE反应哮喘家系成员(39.4%)较家系中非特应症者（12.0％）显著高频表达(t=2.3825,P<0.05)。结论HLA-DQA1*0101,*0601和DQB1*0303,*0601是哮喘遗传易感等位基因;HLA-DQB1*0201限定对屋尘螨抗原特异性IgE反应。     

人类白细胞抗原-DQA1*0301等位基因与腔隙性脑梗死的相关性研究

目的 针对腔隙性脑梗死多基因致病的特点,进行人类白细胞抗原(HLA)-DQA1等位基因分型,分析腔隙性脑梗死的遗传易感性。方法采用聚合酶链反应-序列特异性引物(PCR-SSP)联合技术对62例腔隙性脑梗死患及64名正常对照组进行HLA-DQA1等位基因的基因分型。结果 HLA-DQA1*0301基因频率在腔隙性脑梗死组明显高于正常对照组,原发性高血压阳性家族史的患组明显高于具有阴性家族史的患组,而DQA1*0103基因频率在正常对照组却明显增高。结论 8LA-DQA1*0301基因与腔隙性脑梗死的遗传易感性相关,与具有原发性高血压阳性家族史患的腔隙性脑梗死的发病相关;HLA-DQA1*0103基因可能是腔隙性脑梗死的保护性基因。     

HLA ASSOCIATIONS IN SUBJECTS WITH RHEUMATOID ARTHRITIS AND BRONCHIECTASIS BUT NOT WITH OTHER PULMONARY COMPLICATIONS OF RHEUMATOID DISEASE

We have examined HLA-DR, DQA and DQB variants in 72 controls,153 subjects with RA without extra-articular features and insubjects with the rheumatoid pulmonary complications of interstitialfibrosis (23) peripheral airways disease (13) and in 41 subjectswith RA and bronchiectasis. Subjects with RA alone showed theexpected association with HLA-DR4 (79%) but those with RA andco-existent pulmonary fibrosis were less likely to be DR4 positive(61%). No other HLA-DR variants were significantly increasedin the different disease groups. HLA which types serologicallyas DQw1 was increased in subjects with RA and peripheral airwaysdisease as compared to rheumatoid subjects with normal lungfunction, but these differences were not statistically significant.DQBI*0601 was increased in subjects with bronchiectasis withor without RA (but only significantly so in RA-BR subjects)DQBI*0301, DQBI*020l and DQAI*0501 frequencies were also increasedin subjects with RA and bronchiectasis as compared to thosewith RA alone. KEY WORDS: Rheumatoid arthritis, Pulmonary fibrosis, Obstructive airways disease, Bronchiectasis, HLA-DR, HLA-DQ, HLA-Dw, C4     

HLA class II distribution in Congolese with hyperthyroidism: preliminary results

OBJECTIVE: Incidence of the hyperthyroidism is continuously increasing, whereas our knowledge concerning the facilitating or etiologic factors of this increase are still partial. To evaluate some of these unknown factors, we started this preliminary study, in order to identify HLA genes in hyperthyroid Congolese, and to determine their susceptibilty in the appearance and development of hyperthyroidism at the Hospital Clinic of Kinshasa. MATERIALS AND METHODS: Nine Congolese women with hyperthyroidism, and thirteen healthy controls (3 women and 10 men) were examined and compared for HLA-DR and HLA-DQ genes analyses, from August 2000 to August 2002. DRB1 and DQB1 alleles were identified, using the Polymerase Chain Reaction (PCR) and immobilized sequence-specific oligonucleotide (SSO HLA-DRB1 and DQB1 test) probes assays. RESULTS: In the group with hyperthyroidism, three alleles (HLA-DR1, HLA-DR2, HLA-DR3) and an allele group (HLA-DR11,13,14) were found for DRB1 locus, while only one allele (HLA-DQB1*0602) was identified for DQB1 locus; allele group HLA-DR11,13,14 was the most frequent (allele frequency=0.50), followed by HLA-DR3 allele (allele frequency=0.222); 6 haplotypes were observed, with predominance of haplotype DR3/DR11,13,14 (genotype frequency=0.333), followed by haplotype DR11,13,14/DR11,13,14-DQB1*0602 (genotype frequency=0.222). In the group of healthy controls, three alleles (HLA-DR2, HLA-DR3, HLA-DR4) and an allele group (HLA-DR11,13,14) were identified for DRB1; HLA-DR2 allele was predominant (allele frequency=0.615), followed by allele group HLA-DR11,13,14 (allele frequency=0.231); a statistic significant difference was observed between the frequencies of DR2 allele and allele group DR11,13,14 in the healthy controls compared to those of hyperthyroid patients (p=0.02); 6 haplotypes were also detected in this group, the most frequent haplotype being HLA-DR2/DR2-DQB1*0602 (genotype frequency=0.540 versus 0.333 in the hyperthyroid group) (p=0.048). HLA-DQB1*0602 was dominant in the healthy controls group (allele frequency=0.890), versus HLA-DQB1*0302 (allele frequency=0.110). CONCLUSIONS: HLA-DR2, HLA-DQB1*0602 and DR2/DR2-DQB1*0.602 would play a protective role against the hyperthyroidism, while DR3 allele, allele group DR11,13,14 and haplotype HLA-DR3/DR11,13,14 would predispose to this disease or to Graves' exophtalmopathy. A large and profound study is needed to confirm our preliminary results.     

MHC class II, tumour necrosis factor alpha, and lymphotoxin alpha gene haplotype associations with serological subsets of systemic lupus erythematosus

OBJECTIVE: To conduct a case-control study to investigate whether there are independent tumour necrosis factor alpha (TNFalpha) or lymphotoxin alpha (LTalpha) haplotype associations with SLE or with any of the major serological subsets of SLE. METHODS: 157 patients with SLE were genotyped for HLA-DRB1, HLA-DQB1, TNFalpha, and LTalpha alleles by polymerase chain reaction and compared with 245 normal white controls. For TNFalpha, six single nucleotide polymorphisms (SNPs) at positions -1031, -863, -857, -308, -238, and +488 and for LTalpha three SNPs at positions +720, +365, and +249 were studied to assign six TNFalpha haplotypes (TNF1-6) and four LTalpha haplotypes (LTA1-4). All SLE patients had full serological profiles on serial samples. RESULTS: The most significant association with SLE overall was with HLA-DR3 (p<0.001; odds ratio (OR) = 2.5 (95% confidence interval, 1.6 to 3.8)) and the extended haplotype HLA-DQB1*0201;DRB1*0301;TNF2;LTA2 (p<0.001; OR = 2.3 (1.4 to 3.7)). Associations were strongest in the anti-La positive group (13%) of SLE patients (HLA-DR3, OR = 71 (9 to 539); HLA-DQB1*0201, OR = 35 (5 to 267); TNF2, OR = 10 (2.8 to 36), and LTA2, OR = 4.9 (1.1 to 21)). There was an increase in the HLA-DR2 associated extended haplotype (HLA-DQB1*0602;DRB1*1501;TNF1;LTA1) in patients with anti-Ro in the absence of anti-La (p<0.005; OR = 3.9 (1.5 to 10)). The HLA-DR7 extended haplotype (HLA-DQB1*0303;DRB1*0701/2;TNF5;LTA3) was decreased in SLE overall (p<0.02; OR = 0.2 (0.05 to 0.8)). CONCLUSIONS: The strongest association in this predominantly white population with SLE was between HLA-DR3 and anti-La, which seemed to account for any associations with TNFalpha alleles on an extended DR3 haplotype.     

The clinical and immunogenetic characteristics of adult-onset type 1 diabetes mellitus in Korea

Although the HLA class II alleles and immunological abnormalities are associated with type 1 diabetes mellitus (T1DM) in all racial groups, there are considerable variations in the genotypes and the prevalence of autoantibodies. In order to investigate the characteristics of the immunogenetic patterns and to use these as an early diagnostic tool and guideline for a therapeutic plan, we examined the clinical characteristics and the patterns of anti-GAD antibody (GADA), IA-2 antibody (IA-2A), HLA-DR and HLA-DQ in Korean adult-onset T1DM patients. Adult-onset patients had higher serum C-peptide levels than child-onset patients. In adult-onset patients, the prevalence of GADA and IA-2A were 59.5% and 15.3% respectively, and increased frequencies of HLADR4 and-DR9 were found. The frequencies of HLADQA1,-DQB1 and-DQ heterodimers were similar to those of the control, but child-onset patients had high frequencies of the HLA-DR3,-DR4,-DR9, DQA1*0301, DQA1*0501 and DQB1*0201 genotypes. In conclusion, Korean adult-onset T1DM patients had a lower prevalence of GADA, which was comparable to that found in Caucasian patients. The detection of GADA might help to predict the insulin dependency of adult-onset diabetes. Difference in the frequencies of diabetes associated with HLA type suggests that there might be a heterogeneity in the pathogenesis of diabetes according to the age of onset.     

Analysis by the polymerase chain reaction of histocompatibility leucocyte antigen-DR9-linked susceptibility to insulin-dependent diabetes mellitus.

DNA sequence analysis of class II HLA from Caucasian and black patients with type 1 (insulin-dependent) diabetes mellitus has suggested that aspartic acid at position 57 (Asp 57) of the DQ beta chain provides protection against insulin-dependent diabetes mellitus (IDDM). In contrast, most Japanese patients with IDDM have Asp 57-positive alleles. To determine the reason for the differences and to localize the HLA-linked diabetogenic gene in Japanese, we studied the DQA1 and DQB1 genes of Japanese patients with IDDM and control subjects by the polymerase chain reaction in combination with restriction fragment length polymorphism analysis. Associations of DQA1*0301 and DQB1*0303 with IDDM were observed. DQA1*01 was associated negatively with IDDM. The HLA-DR9 haplotype, which is associated positively with IDDM in Japanese, was associated with DQA1*0301 and DQB1*0303, indicating that the Japanese DR9 haplotype is the same as that in caucasians but different from that in blacks. Of the loci on Japanese DR9 haplotypes, the DQA1*0301 allele showed the highest association with IDDM. DQB1*0303 was also positively associated with IDDM. Since DQB1*0303 is identical to DQB1*0302 except that it contains Asp 57, the data suggests that an Asp 57-positive allele confers susceptibility to IDDM when the whole molecule of the DQ beta chain is similar to other susceptible DQ beta chains. DQA1*0301 appears to be a marker of IDDM in all these populations: Japanese, caucasian, and black.     

中国人群1型糖尿病HLA-DQ基因多态性的Meta分析

目的　综合评价中国人群HLA DQ基因多态性与 1型糖尿病 (DM)的关联性。方法　以 1型DM组和健康对照组的各HLA DQ等位基因频数(基因型频数、单倍型频数 )分布的OR值为统计量,全面检索相关文献;应用Meta分析软件包REVMAN4. 2,在基因分型水平上,对各研究的结果进行一致性检验和数据合并,并评估发表偏倚。结果　等位基因DQA1* 0301、DQA1* 0501、DQB1* 0201、DQB1* 0303、DQB1* 0401和DQB1* 0604是中国人群 1型DM的危险基因 (均P<0. 05), 他们的合并OR值分别为2. 83、2. 90、4. 17、1. 65、2. 00和 3. 00;基因型 (或单倍型 )DQA1* 0301 /DQB1* 0201、DQA1* 0301 /DQB1*0302、DQA1* 0501 /DQB1* 0201、DQA1* 0301 /DQB1* 0201 /DRB1* 0301和DQB1* 0302 /DRB1* 0405是中国人群 1型DM的危险基因型(或单倍型,均P<0. 05),他们的合并OR值分别为 8. 95、3. 09、6. 01、6. 57和 14. 85。而等位基因DQA1* 0101、DQA1* 0102、DQA1* 0103、DQA1* 0104、DQA1* 0201、DQA1* 0401、DQA1* 0601、DQB1* 0301、DQB1* 0501、DQB1* 0503、DQB1* 0601和DQB1* 0602是中国人群 1型DM的保护等位基因(均P<0. 05),他们的合并OR值分别为 0. 47、0. 38、0. 21、0. 07、0. 44、0. 39、0. 44、0. 19、0. 33、0. 32、0. 42和 0. 28; 基因型     

Genetic analysis of HLA class II alleles and susceptibility to Type 1 (insulin-dependent) diabetes mellitus in Japanese subjects

Summary Although HLA-DQB1 alleles encoding aspartic acid at position 57 (Asp-57) are protective against Type 1(insulin-dependent) diabetes mellitus in Caucasians, most Japanese Type 1 diabetic patients carry at least one Asp-57 DQB1 allele. We analysed the DRB1, DQA1 and DQB1 genes of 99 Japanese patients and 86 control subjects with polymerase chain reaction and sequence-specific oligonucleotide hybridization. We found that (1) the DQA1*0301 allele was significantly increased in Type 1 diabetic patients (RR 7.8,pc < 0.0001); (2) the DRB1*0405 (Dw15) allele, which is a subtype of DR4 haplotype, was significantly increased in DR4-positive patients (RR 12.0,pc < 0.001); and (3) although the DRw8-DQw8 haplotype was positively associated with Type 1 diabetes, the DRBl*0406-DQw8 haplotype was decreased in the diabetic patients. These data indicate that DRB 1 and DQA1 genes also confer susceptibility to Type 1 diabetes in Japanese.     

Inheritance of MHC class II genes in IDDM studied in population-based affected and control families

Summary The transmission of HLA-DR and DQ was compared between 46 families with at least one child affected by insulin dependent diabetes mellitis (IDDM) and 43 healthy control families. In the patient families, there was an increased transmission of DR4 (p<0.025) and DQB1*0302 (p<0.01) from both parents to the index patient. There was an increased transmission of DQB1*0302 (p<0.03) from the mothers only. The non-inherited maternal haplotypes showed a significantly decreased frequency (p<0.01) of positively associated haplotypes (DR4-DQA1* 0301-DQB1*0302, DR3-DQA1*0501-DQB1*0201) compared to all parental haplotypes in the control families. In the control families neither transmission rates nor frequencies of non-inherited haplotypes differed from those expected in the control families. In conclusion, the observed reduction of IDDM-positively associated haplotypes in patient non-inherited maternal haplotypes, but not in non-inherited paternal haplotypes, suggests that tolerance during fetal life to maternal non-inherited HLA molecules may be important to diabetes development.Abbreviations HLA Human Leucocyte antigen - NIMH non-inherited maternal haplotype - NIPH non-inherited paternal haplotype - MHC major histocompatibility complex - RPE relative predispositional effect - RFLP restriction fragment length polymorphism - w/v weight volume     

Distribution and frequency of HLA alleles and haplotypes in Brazilians with type 1 diabetes mellitus

The genetic predisposition to type 1 diabetes (DM1) is associated with genes of the human leukocyte antigen (HLA) system, specially the HLA-DR and -DQ. In Caucasians, the HLA-DR3 and -DR4 antigens are associated with susceptibility and the -DR2, with protection. In Brazil, a country with a large miscegenation of European Caucasians, Native Amerindians and African Blacks, the genetic basis of DM1 has not been adequately studied. The aim of this paper is to present a critical review of articles indexed in the MEDLINE and LILACS-BIREME data basis about the association of HLA with DM1 in Brazilians. Eight papers, all of them from the Southeast region, were found. Immunogenetic susceptibility to DM1 in Brazilians was associated with HLA-DRB1*03, -DRB*04, -DQB1*0201, -DQB1*0302 alleles, and protection against DM1 was associated with HLA-DQB1*0602, -DQB1*0301 alleles and -DR2 and -DR7 antigens. Since the Brazilian population is not racially homogeneous, it is not possible to extrapolate studies from a single region to the remainder of the country. It is necessary to study populations from different regions to identify new associations or to strengthen associations with the ones already identified. This knowledge will contribute to future prophylactic or therapeutic interventions in the group of Brazilians at risk of developing DM1.