Dissertation > Medicine, health > Internal Medicine > Systemic disease > Autoimmune diseases > Autoimmune diseases, connective tissue disease > Lupus erythematosus > Systemic lupus erythematosus

Genetic Variation in CD226 Gene and Systemic Lupus Erythematosus

Author DuYan
Tutor ShenLingXun
School Huazhong University of Science and Technology
Course Internal Medicine
Keywords PCR RFLP Systemic lupus erythematosus CD226 gene SNP Real-time PCR
CLC R593.241
Type Master's thesis
Year 2011
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Systemic lupus erythemtosus (SLE) is a chronic autoimmune disease associated with high titers of antinuclear antibodies and the clinical involvement of many organs and tissues. Epidemiological evidence, together with recent linkage and association studies, suggests that susceptibility to SLE in humans is strongly in?uenced by genetic factors. The major histocompatibility complex (MHC) and the human leukocyte antigen (HLA) system have been confirmed as important genetic risk factors associated with SLE. However, the HLA system constitutes 40% of the overall estimated genetic risk for SLE, and it has been suggested that a substantial proportion of SLE genetic susceptibility is encoded by non-HLA genes. The rs763361 single nucleotide polymorphism (SNP) within the CD226 gene has recently been reported as a novel susceptibility locus for multiple autoimmune diseases such as type 1 diabetes (T1D), rheumatoid arthritis (RA), autoimmune thyroid disease (AITD) and multiple sclerosis (MS) in European Caucasian populations.CD226 (also known as DNAX accessory molecule 1, DNAM-1) is a 67-kDa type I membrane protein involved in the adhesion and co-stimulation of T cells (6). It is constitutively expressed on the majority of natural killer (NK) cells, CD4+ and CD8+ T cells, monocytes, platelets and a subset of B cells. It has also been reported that CD226 expression deficiency causes high sensitivity to apoptosis in NK T cells obtained from patients with SLE, providing supporting evidence for the role of CD226 in autoimmune diseases.The research will identify CD226 gene variant that related to SLE in Han population in China for the first time .At the same time, whether the CD226 gene variant may affect the expression of CD226 and then cause many clinical manifestations will also be researched. The details are shown as the following two parts: Objective: rs763361 of CD226 gene will be inspected in the Chinese group. The purpose is to get the relationship of CD226 single nucleotide polymorphism with SLE affectability.Patients and Methods: Refer to 1982 amended ACR standard. 261 SLE patients are collected from clinic and in-patients, normal collators are 279 samples.rs763361 site of CD2226 gene will be inspected by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The Pearson chi-squared test, implemented using plink software (http://pngu.mgh.harvard.edu, version 1.06), was used to compute the P value and the corresponding odds ratios (ORs) with 95% confidence intervals (CIs) for allelic associations. The Hardy–Weinberg linkage disequilibrium test was also carried out using plink software in the case and control groups.Results: The genotype distribution did not deviate from the Hardy–Weinberg equilibrium in both groups (P=0.71 and P=0.18 for patients and controls, respectively). The SLE patients group showed an increased frequency of the T allele compared with the control group, and the OR for the T allele compared with the C allele was 1.34 (P=0.018). The frequency of the TT genotype was higher in SLE patients than in the control subjects (P=0.025, OR=1.79, 95%CI=1.07–3.01). In SLE patients with anti-dsDNA positive, the T allele and TT genotype were both higher than those with anti-dsDNA negative (P=0.003 and P=0.015 for T allele and TT genotype respectively).Conclusion: In Chinese Han population, rs763361 of CD226gene is associated with SLE, it is also associated with the production of anti-dsDNA, thus the functional study of this gene may provide clues to the mechanism of autoimmune diseases. Objective: To investigate the expression levels of CD226 mRNA in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE), the relation between the gene expression and disease activity is explored, and the relation between the gene expression and Gly307Ser polymorphism of CD226 is also examined.Methods: CD226 gene is measured using real-time polymerase chain reaction (qRT-PCR) in PBMCs. The expression levels of CD226 gene in PBMCs were compared between 90 SLE patients and 30 healthy individuals.Results: The expression level of CD226 in the PBMCs of SLE patients significantly decreased compared to healthy individuals (P<0.001), while there may be no difference among three different genotypes in the CD226 expression (P>0.05). No correlation between ESR, CRP, ANA, SLEDAI scores, C3 and the expression level of CD226 gene (P>0.05).Conclusion: In Chinese Han population, CD226Gly307Ser locus is associated with the development of SLE, while the role of CD226 gene in autoimmune diseases to be discussion in future.

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