YULIASIH (2010) SINGLE NUCLEOTIDE POLIMORPHISMS PROMOTER GEN IL-10 SEBAGAI PREDIKTOR AKTIVITAS PENYAKIT SYSTEMIC LUPUS ERYTHEMATOSUS. Disertasi thesis, UNIVERSITAS AIRLANGGA.

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Abstract

Background : Systemic Lupus Erythematosus is a complex diseases, signifying that genetic and environmental factors are involved in diseases development. Although the role of genetic factor in many populations have been studied, the genetic factor associated with diseases activity is yet to be identified. Several study reported the association between serum level of IL-10 with SLE disease activity. This study was performed to determined polymorphisms in the IL-10 gene promoter with diseases activity SLE in Javanese population. Methods : This study was performed in two procedures. The first procedure analyzed the genotype IL-10 gene proximal promoter in SLE patients using a pair of specific primer of the IL-10 gene proximal promoter and sequenced by Applied Biosystem method. The second procedure analyzed the influence of IL-10 in converting from anti-inflammatory into pro-inflammatory function using PBMC. This study enrolled 47 SLE patients (ACR criteria) in active diseases, dr Soetomo hospital Surabaya. Disease activity was evaluated using SLAM. The level of IL–10 was measured by Eliza kit. Result : This study showed that there is no significant association between level of IL-10 with ANA and dsDNA, but the level of IL-10 was significant association with low level complement. There were three locus SNP at -294 A-G, -296 A-T and -301 A-G of IL-10 gene proximal promoter, with three variant combination: -294 A-G, -296 A-A, -301 A-G; -294 A-G, -296 A-T, -301 A-G and -294 A-A, -296 A-A, -301 A-A. The serum level of IL-10 among three group were significantly difference. The patients with variant -294 A-G, -296 A-A, -301 A-G had more significantly higher score of disease activity (severe diseases) compare with the other groups of patient. The combination -294 A-A, -296 A-A, -301 A-A is similiar to the sequence IL-10 gene proximal promoter from GenBank NCBI. The result of the study showed that interferon significantly induced pro-inflammatory function of IL-10. Conclusion : This study result is Interleukin-10 proximal promoter SNP implicates diseases activity of Systemic Lupus Erythematosus by increasing the level of IL-10. Interferon converting the function of increasing level IL-10 as pro-inflammatory.

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