Systemic lupus erythematosus: genetic variants in Xq28 region

Noha A Doudar; Sanaa S Abdelshafy; Shaimaa A K Rady; Asmaa M Mokhtar

doi:10.5114/reum.2019.89517

Systemic lupus erythematosus: genetic variants in Xq28 region

Reumatologia. 2019;57(5):264-270. doi: 10.5114/reum.2019.89517. Epub 2019 Oct 31.

Authors

Noha A Doudar¹, Sanaa S Abdelshafy¹, Shaimaa A K Rady², Asmaa M Mokhtar¹

Affiliations

¹ Department of Clinical and Chemical Pathology, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt.
² Department of Rheumatology, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt.

Abstract

Objectives: Methyl-CpG-binding protein 2 (MECP2) and interleukin-1 receptor-associated kinase (IRAK1) are encoded by adjacent X-linked genes and recognized for their role in regulation of inflammation. The present case control study was conducted to detect the genetic association between MECP2 (rs1734791) and IRAK1 (rs1059703) single nucleotide polymorphisms (SNPs) and susceptibility to systemic lupus erythematosus (SLE), and the possible association of these SNPs and severity of SLE.

Material and methods: Fifty patients with SLE and 100 healthy controls were included in this study. Systemic Lupus International Collaborating Clinics (SLICC) criteria were used to classify SLE patients and the activity of the disease was assessed by SLEDAI score. Disease severity was assessed by the SLICC damage index (SLICC DI). Genetic association of both SNPs with SLE was assessed by Taq Man allelic discrimination technique.

Results: Analyses of MECP2 (rs1734791) SNP genotypes revealed that homozygous TT genotype was significantly higher in the control group than SLE patients (p < 0.001, odds ratio [OR] = 0.120). Frequency of allele (A) was significantly higher in SLE patients, (p < 0.001, OR = 0.334). SLE patients had significantly higher frequency of the homozygous AA and heterozygous AG genotype of IRAK1 (rs1059703) SNP in comparison to healthy controls (p = 0.0029, OR = 4.17 and 6.30 respectively). T+G and T+A of rs1734791 and rs1059703 SNPs are protective haplotypes (OR = 0.47 and 0.3, p = 0.0046 and < 0.012 respectively). No significant association between either SNP and disease activity or severity was found.

Conclusions: There is a possible genetic association between both rs1734791 and rs1059703 SNPs and susceptibility to SLE, while no significant association between either SNP and disease activity or severity was detected.

Keywords: inflammation; interleukin 1 receptor-associated kinase; methyl-CpG-binding protein 2; systemic lupus erythematosus.