Associated Study Between Polymorphisms Of STAT4 And Systemic Lupus Erythematosus In The Han Population Of Yunnan Province

Objective To investigate the association between single nucleotide polymorphism(SNP) in STAT4(signal transducer and activator of transcription) gene and systemic lupus erythematosus (SLE) susceptibility in Chinese Han population of Yunnan. To investigate the STAT4 mRNA expression levels, the serum level of IL-12 and IFN-y in peripheral blood of patients and normal individuals, and to explore its possible role in the pathogenesis of SLE.Methods The Sequenom MassArray system was used to genotype 20 single nucleotide polymorphism of the STAT4 genes(rs10168266, rs10181656, rs11889341, rs13017460, rs1551443, rs16833249, rs2459611, rs3024879, rs3024886, rs3024894, rs3024895, rs3024933, rs3821236, rs4555370, rs6712821, rs7568275, rs7574865, rs7599504, rs8179673, rs932169)in 378 SLE cases and 389 normal controls. STAT4 expression of SLE patients and normal controls were analyzed with QPCR technique. ELISA was applied to determine the serum level of IFN-y and IL-12. The data was analyzed with the Plink 1.06 software and spss 16.0.Results 1. The six SNPs of STAT4 gene tested here were significantly associated with SLE, particularly rs10181656 (P=5.41E-09), and the association with SLE was significantly higher than that of European.2. When patients were distribute in subgroup according to arthritis, butterfly rash, kidney damage, oral ulcers, anti-dsDNA, ANA, hematological and serositis, the G-allele frequencies of SNP rs10181656 was significant differences between SLE patients and controls (P<0.0001).3. The expression level of STAT4mRNA of SLE patients was significantly higher than that of control groups (P< 0.01). There was correlation between STAT4 and SLEDAI(r=0.385, P<0.05).4. The G-allele of rs10181656 increased the expression of STAT4mRNA.5. The levels of IFN-y and IL-12 of SLE patients were significantly higher than that of normal controls (P<0.01), The level of IFN-y and IL-12 positive correlated to SLEDAI (P<0.05).6.The expression level of STAT4mRNA show a positive correlation with IFN-r (r=0.335,P=0.009) and IL-12 (r=0.401,P=0.002), and show a positive correlation with serositis, hematological, kidney damage and butterfly rash(P<0.05).Conclusion 1. It suggests that polymorphism of STAT4 gene may be related to susceptibility of SLE in Chinese Han population of Yunnan. The G-allele of rs10181656 increases the risk of SLE patients with arthritis, butterfly rash, kidney damage, oronasal ulcers, anti-dsDNA, ANA, hematological and serositis.2. The level of STAT4 mRNA of SLE increases and correlates with SLEDAI, so the level of STAT4 might be used as a referential indicators, which suggested that they may take part in development of SLE and correlate with the severity of SLE.3. The serum level of IFN-r and IL-12 increase, and show a positive correlation with SLEDAI. It suggests that IFN-r, IL-12 may be as a parameter of SLE activity. According to the mRNA expression level of STAT4 associated with IFN-r and IL-12, we conclude that STAT4 may have active effect on IFN-r and IL-12 in the gene level. STAT4 may regulate IFN-r, IL-12 and enhance the mRNA expression of tow cytokines.