HLA-DRB GENES POLYMORPHISM IN CHINESE NORTHERN PATIENTS WITH ATOPIC ASTHMA

Objective. Atopic asthma provides a useful model for evaluating the genetic factors that control human immune responsiveness. HLA class Ⅱ gene products are involved in the control of immune response. As HLA-DRB gene is the most polymorphic HLA class Ⅱ gene, we investigated whether susceptibility or resistance to the disease is associated with HLA-DRB. Methods. Blood samples were obtained from two groups of unrelated Chinese northern adults: （l） 50 atopic asthma （7 of them with familial aggregation） ;（2） 80 healthy controls without asthma or atopy and other HLA-associated diseases. Genomic DNA was extracted from peripheral venous blood leucocytes. The polymorphic second exon of HLA-DRB gene was amplified by sequence-specific primer polymerase chain reaction （SSP/PCR） methods. All patients had their serum IgE （total and specific） antibody levels by RAST, bronchial reactivity assessed by methacholine brocho-provocation test and/or bronchodilation test. Results. There was an increased gene frequency of DR6（13） and DR52 in asthmatic subjects compared with healthy subjects（17% vs 4. 3%, P<0.01; 50% vs 17. 5 %, P<0. 01 ）, and the decreased frequency of DR2（15） and DR51 in asthmatic patients（7% vs 18%, P<0. 05; 2 % vs 33 %, P<0. 01 ）. We found the positive association between DR6（13）-DR52 and sIgE antibody responsiveness to dl （from house dust mite al- lergen ）; negative association between HLA-DRB alleles and TIgE or BHR （bronchial hyperresponsiveness ）. Conclusion. The results suggested that HLA haplotype DR6（13）-DR52 was significantly implicated in sus- ceptibility to house dust mite induced-asthma, at least it would be more closely associated with atopic asth- ma. Conversely, alleles DR2（15） and DR51 might confer protection against the disease. HLA-DRB genes were particularly involved in regulating human atopic immune response in asthma.

THE POLYMORPHISMS OF HLA-DR AND TNF B LOCI IN NORTHERN CHINESE HAN NATIONALITY AND SUSCEPTIBILITY TO SYSTEMIC LUPUS ERYTHEMATOSUS

With the aid of methods of polymerase chain reaction / sequence specific primers (PCR/SSP) and polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP), the allelic polymorphism of HLA-DR and TNFB loci and susceptibility to systemic lupus erythematosus (SLE) in northern Chinese Han nationality were studied. The genetic analysis of 51 patients with SLE and 106 healthy controls indicated that frequencies of DR2 and DR3 alleles were significantly increased in SLE patients(P< 0.05 and <0. 005, relative risks of 1.77 and 4.01 respectively), which represent candidate susceptible genes or useful marker for SLE. The frequency of DR5 was found to decrease in SLE patients compared with control population (P<0. 025,relative risk = 0. 38). It might be an antagonistic or protective allelle or a marker for such allele. Analysis of 51 patients with SLE and 80 healthy control also revealed that the frequency of TNFB' 2 allele was significantly increased(P<0. 05,RR= 1. 70). Therefore TNFB' 2 gene may also be a susceptibility gene or a marker gene for SLE in northern Chinese Han nationality. It was also investigated the association between HLA-DR,TNF B alleles and Patient plasmic SC5b-9 levels,auto-antibodies (anti-SSA,SSB,Sm,RNP,ds DNA and ANA) and SLE complications (SLE nephritis,SLE pneu-monitis and SLE encephalopathy) ,no relationship was found.

HLA-DQA1 Polymorphism in Idiopathic Dilated Cardiomyopathy

To determine whether the possession of certain HLA-DQA1 alleles was associated with the risk of developing idiopathic dilated cardiomyopathy (IDC) and to substantiate the role of an autoimmunologic pathogenesis in IDC. Type the alleles of HLA-DQA1 by polymerase chain reaction with sequence-specific primers (PCR-SSP) technique in 38 patients of idiopathic dilated cardiomyopathy (7 women and 31 men), aged from 17 to 56 years old with diagnosis being according to World Health Organization criteria (IDC group), in 50 patients of end-stage heart failure of known etiology (18 women and 32 men), with ages ranging from 34 to 72(HF group), and in the control group consisting of presumably 100 healthy subjects (39 women and 61 men) from the health survey, aged from 30 to 59 years old. The frequency of HLA-DQA1*0501 in the DCM patients was significantly elevated than that in the HF and the control group. Molecular analysis of the DQA1 gene polymorphism performed in the three subgroups shows an increased frequency of DQA1*0501 among patients with less EF. The HF group carries a high frequency of HLA-DQA1*0301. An increased frequency of DQA1*0201 and DQA1*0103 was found in the control group. HLA-DQA1*0501 is an associated gene of idiopathic dilated cardiomyopathy and the possession of DQA1*0301 may be indicative of the known etiologic heart failure, suggesting that the mechanisms involved in the pathogenesis of IDC and otherwise heart failure are different. Immunologic abnormalities may be a major contributor to the susceptibility of developing of IDC.