Association between IKZF1 related gene polymorphism, DNA methylation and
rheumatoid arthritis in Han Chinese: A case-control study.
Abstract
Background: Rheumatoid arthritis (RA) is a systematic autoimmune disease
with evidence of genetic predisposition. The IKZF1 (IKAROS family zinc
finger 1 (Ikaros)) gene is located at chromosome 7, encodes a
transcription factor related tochromatin remodeling, regulates
lymphocyte differentiation, and is associated with some autoimmune
diseases. However, there were few studies reported the association
between IKZF1 and the risk of RA in China. For this, we determined to
investigate the possibility of association between the IKZF1 locus and
RA. Methods: we selected one single nucleotide polymorphisms (SNP) in
the IKZF1 locus, rs1456893, based on a detailed analysis of genome-wide
association study (GWAS) data and performed genotyping in 410 RA
patients and 421 healthy controls in Han Chinese. We studied the
systematic genome-wide interrogation of DNA methylation between RA group
and control group and we also studied the association between CpGs and
RA. Results: The results showed that the rs1456893 locus was correlated
with RA in different models(P<0.05). Through comparison with
methylation levels determined in their equivalent healthy counterparts
we have identified and validated a restricted set of CpGs that show
distinct methylation differences between patients with RA and control
group. The Multiple logistic regression results showed CpG_3
(OR=3.17,95%CI=1.05-9.60,P=0.041) and
CpG_13.14(OR=4.96,95%CI=1.77-13.86,P=0.002)were associated with RA.
Conclusion: IKZF1 can be used as a marker for the diagnosis of RA.
Higher CpG_3 and CpG_13.14 methylation levels would increase the risk
of RA.