Associations of IRF7/KIAA1542 and STAT4 polymorphisms with systemic lupus erythematosus in Chinese Han population / 中华检验医学杂志

ABSTRACT

Objective To investigate genetic polymorphisms of IRF7/KIAA1542 (rs4963128, rs2246614) and STAT4 (rs7574865) and their relationships with lupus nephritis and various autoantibodies present in Chinese Han population of SLE patients. Methods A total of 748 SLE patients and 750 healthy controls belonging to the Chinese population were enrolled into this study. They were genotyped using MALDI-TOF-MS method. Autoantibodies including anti-SSA, anti-SSB, anti-Sm, anti-RNP and anti-dsDNA were determined either by indirect immunofluorescence or double immunodiffusion methods. Results In the healthy group, rs7574865 (STAT4) T/T, T/G, G/G genotype frequency and T, G allele frequencies were as follows: 9.4% , 45. 6% , 45. 0% , 32. 2% , 67. 8% , the corresponding case group as follows: 17.0% , 48.1%, 34.9%, 41.0%, 59.0%, genotype and allele frequencies were significantly different (x2 = 26.30, P<0.01). Compared with the control group, in the case group, T/T genotype frequency and T allele frequency were significantly increased, and in three genetic models ( additive model, dominant model, recessive model), the genotype frequencies were significant difference (P <0. 01). Two polymorphic loci of rs4963128 and rs2246614 (IRF7/KIAA1542) were not statistically significant (x2 =4.49,5.32,P>0.05) in case group and control group, but the rs2246614 genotype frequencies had a statistically significant in recessive model (P <0. 05) , whereas rs4963128 genotype frequencies was no significant difference in the three genetic model (P=0.068, 0.958, 0.067, respectively). In the clinical subphenotype analysis, IRF7/KIAA1542 (rs4963128) in lupus nephritis group (OR = 2. 69, 95% CI = 1. 89-3. 82, P < 0.01) ,anti-SSA antibody group ( OR = 0. 61, 95% CI = 0. 43-0. 87, P < 0. 05 ) and anti-SSB antibody group ( OR =0. 36, 95% CI = 0. 23-0. 56, P < 0.01) of the analysis were statistically significant. At the same time, IRF7/KIAA1542 (rs2246614) in the joint comparison of positive and negative symptoms were also statistically significant (OR=1.34, 95% CI = 1. 06-1. 69, P < 0. 05). Conclusions This findings provide strong evidence suggesting that STAT4 ( rs7574865 ) is the susceptible factor of SLE in Chinese Han population. However, there is not a significant relationships between IRF7/KIAA1542 (rs4963128, rs2246614) polymorphisms and the risk of SLE, but the associations of IRF7/KIAA1542 (rs4963128, rs2246614) with the a variety of clinical subphenotypes, such as lupus nephritis, joint symptoms and production of anti-SSA antibody and anti-SSB antibody implicates IRF7/KIAA1542 as a putative candidate gene of SLE.