| Summary: | 碩士 === 國立臺灣大學 === 醫學檢驗暨生物技術學研究所 === 96 === Growth arrest specific gene 6, a member of vitamin K-dependent protein family, is expressed in endothelial cells, macrophage, lung, intestine and bone marrow in a secreted form. Gas6 can function as bridging molecule between phosphatidylserine (PtdSer) on the apoptotic cells and Mer receptor on macrophages.Systemic lupus erythematosus(SLE) is an autoimmune disease characterized by chronic systemic inflammation resulted from autoreactive lymphocytes, autoantibodies and immune complexes. Ineffective clearance of apoptotic cells which leads to the release of self-antigen, may be important in the development of lupus-like autoimmune disease in mice. In this study, we intend to investigate whether serum Gas6 level and genetic variation in Gas6 are associated with prevalence or disease activity of human SLE.
Seral Gas6 level and the single nucleotide polymorphisms (SNPs) on Gas6 gene were investigated in 83 SLE patients and 40 non-lupus control subjects. Elevated serum Gas6 level was noted in 40.96% of SLE patients as compared with the non-lupus control.(SLE: 24.51±14.06ng/mL versus non-lupus control: 18.44±6.29 ng/mL, p≦0.0001). Correlation between serum Gas6 and ESR/CRP was also analysed. Serum Gas6 level is unlikely to be associated with inflammatory states in SLE. Furthermore, SLE patients with high disease activity index (SLEDAI>6), lupus nephritis or vasculitis showed higher serum Gas6 level than the other SLE patients. (high SLEDAI group: 25.65±14.77ng/mL versus low SLEDAI group: 20.89±8.70ng/mL, p=0.0092; nephritis group: 27.40±14.70ng/mL versus non-nephritis group: 23.52±13.51ng/mL, p=0.0286; vasculitis group: 28.55±14.54ng/mL versus non-vasculitis group: 23.71±13.69ng/mL, p=0.0287).Two single nucleotide polymorphisms (SNPs), intronic Gas6 834+7G/A and synonymous Gas6 1332C/T were studied. The genotyping results indicate that Gas6 834+7 A allele is positively associated with thrombocytopenia in SLE patients (odds ratio=3.05, 95% CI: 1.02-9.13, p= 0.047) and Gas6 1332 T allele was positively associated with vasculitis in SLE patients (odds ratio=3.07, 95% CI: 1.25-7.56, p=0.013). Furthermore, SLE patients with Gas6 834+7GA/AA genotype showed higher serum Gas6 level as compared to the SLE patients with a GG genotype (834+7GA/AA group: 27.03±16.44ng/mL, 834+7GG: 22.94±11.43ng/mL, p=0.0168). Conclusion: 1. Elevated serum Gas6 level was noted in some of SLE patients and did not completely result from inflammation. Elevated serum Gas6 level may be associated with SLE development. 2. SLE patients with lupus nephritis or vasculitis showed higher serum Gas6 level than the other SLE patients. 3. Gas6 SNP 1332C/T and 834+7G/A are positively associated with vasculitis and thrombocytosis, respectively.
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