Presentation: Association Of DNase IV Polymorphism With Autoantibodies In Systemic Lupus Erythematosus Patients (2007)

813 Association Of DNase IV Polymorphism With Autoantibodies In Systemic Lupus Erythematosus Patients

PURPOSE: DNase IV is an important enzyme for DNA metabolism and also often called as flap endonuclease-1 (FEN1). Given that decreased activity of Crn-1 (C. elegans FEN1 homologue) has been shown to resist to DNA degradation in apoptotic cells, DNase IV (FEN1) may be associated with autoimmune diseases such as systemic lupus erythematosus similar to those observed in DNase I. Therefore, genetic polymorphism of DNase IV and relationship with SLE and autoantibody were investigated.
METHODS: A total of 532 SLE patients and 520 healthy controls in Korean population were enrolled. We sequenced whole coding sequence of the DNase IV gene, including the promoter region (~1.5 kb), to discover genetic variants in 24 Korean DNA samples. Multiple logistic regression analysis was performed to examine the genetic association with SLE and autoantibody (anti-Sm, anti-RNP, anti-Ro, anti-La, and anti-dsDNA Abs), using age, sex, and disease duration as covariates. P-values of codominant, dominant, and recessive models were also calculated.
RESULTS: We found three single-nucleotide polymorphisms (SNPs) [-2753G>A, +147T>G (Gly49Gly) and +1466G>T] and three haplotypes. Two of these polymorphisms (-2753G>A and +147T>G) were selected for a larger-scale genotyping (532 SLE patients and 520 healthy controls) on the basis of their allele frequencies, linkage disequilibria among SNPs, and haplotype-tagging status. -2753G>A was not associated with risk of SLE [codominant model odds ratios (95% confidential interval) 1.03(0.86-1.23), P=0.76; dominant model OR (95%CI) 1.07(0.84-1.37), P=0.58; recessive model OR (95%CI) 0.96(0.66-1.40), P=0.84], but show significant associations with an increased risk of anti-Sm [codominant model OR (95%CI) 1.89 (1.28 -2.79 ), P=0.001; dominant model OR (95%CI) 2.17 (1.20 -3.90 ), P=0.01; recessive model OR (95%CI) 2.62 (1.33 -5.17 ), P=0.006] and anti-RNP Abs [codominant model OR (95%CI) 1.34 (1.00 -1.79 ), P=0.05; dominant model OR (95%CI) 1.24 (0.83 -1.86 ), P=0.30; recessive model OR (95%CI) 2.04 (1.16 -3.59 ), P=0.01].
CONCLUSIONS: In conclusion, three SNPs were identified and -2753G>A was significantly associated with an increased risk of anti-Sm and anti-RNP Abs in SLE patients.

 I. Kim, None; H. Kim, None; H. Yun, None; H. Shin, None; B. Park, None; H. Cheong, None; S. Bae, None.