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Experimental Studies On HLA Genotyping In Patients With Psoriasis Vulgaris In Chinese Han Population

Posted on:2003-11-20Degree:DoctorType:Dissertation
Country:ChinaCandidate:A P ZhangFull Text:PDF
GTID:1104360065460896Subject:Dermatology and Venereology
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Accumulative evidence of the genetic epidemiological investigation and twin studies indicate that psoriasis is characteristic of higher heritable predisposition and familial aggregation. A number of environmental factors, such as infection, skin injury and stress, contribute to the development of this disease. Animal model experiments and cellular tests in vitro have shown that abnormal activation of T lymphocyte may play a pivot role in triggering the pathogenesis of psoriasis. At present, most of researchers are inclined to this notion that psoriasis is a chronic, inflammatory, hyperproliferative skin disorder which is caused by T-cell dysfunction with the induction of the interplay of genetic and environmental factors, in that the genetic genes are considered to constitute one of main causes of susceptibility to psoriasis. However, the genetic background to this disease is very complex, because multifactorial or polygenic control is not only involved in the pathogenesis of this disease, but the genetic heterogeneity is greater between patients and families, and the distribution with prevalence varies according to race and geographical location. Therefore, searching some components associated with psoriasis, mapping susceptibility loci and identifying its genes have become the core of elucidating the etiology and molecular mechanism and determining the target of specific therapy.The genes encoding the HLA (human leukocyte antigens) are parts of the MHC (major histocompatibility complex) and are located on the short arm of chromosome 6, which have highly polymorphisms. HLA complex comprises class I determinants (HLA-A, -B and -C), class II determinants (HLA-DR, -DQ and -DP), and class III determinants such as tumor necrosis factor (TNF), B-associated transcript (BAT), and heat-shock protein (HSP). HLA antigens and some cytokines are known to play important roles in immune response and immunoregulation, or inflammation of the human body. It is evidenced that the association of HLA complex with many autoimmune diseases is the very tightest of all human genome, i.e. HLA complex is recognized to be a mainly heritable region of susceptibility to disorders.Since the correlation of HLA-B13 antigen with psoriasis was first conformed in the seven decades last century, subsequent studies on association of HLA antigens with psoriasis had become a hotspot in this aspect. But the early research was focused to the relationship of HLA phenotype to psoriasis because of using serological method in that time, and the etiology of psoriasis was not further recognized. Recently, HLA genotyping has been extensively carried out by PCR-based method so that the association of HLA genes with this dermatosis has been greatly developed on the level of DNA molecule, which provides the basis for exploiting the genetic susceptibility to psoriasis and mapping susceptibility loci to it by way of genome-wide scan.Psoriasis vulgaris (PV) is a common subtype of psoriasis, approximately accounting for 97 per cent of psoriasis, and has been extensively investigated. This program presented here aims at typing HLA genes systematically among 166 unrelated Han's patients withPV from Anhui province using by PCR-SSP (sequence-specific primers) and PCR-RFLP (restriction fragment length polymorphism) techniques. Our studies were divided into 4 parts as followings: 1. Studies on HLA-C Locus Alleles are Associated with Genetic Susceptibility to Psoriasis Vulgaris in Chinese Han PopulationHLA-C locus, one of traditional MHC class I region, is located on the tolemere to chromosome 6 short arm, nearing to HLA-B locus. This locus has highly genetic polymorphisms. At present, of association of HLA-C with PV, the largest and most consistently reported heritably relative risk (RR) factors for psoriasis have been shown for the HLA-Cw*0602 allele. This alleles has been considered to be a genetic marker of PV in most ethnic groups, where the linkage disequilibrium between PV and other HLA-C antigens varies significantly across racial an...
Keywords/Search Tags:Psoriasis vulgasris, HLA allele, PCR-SSP, PCR-RFLP, Class Ⅰ molecule, Class Ⅱ molecule, TNF-alpha, Class Ⅲ gene polymorphism
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