The Role of MECP2 and CCR5 Polymorphisms on the Development and Course of Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a chronic and systemic autoimmune disease. SLE is described by production of autoantibodies and causes damage of many organs. T-cells play a crucial role in SLE pathogenesis. T-cells intensify inflammation through a number of processes, which leads to autoimmunization. CCR5 and MECP2 genes are linked with T-cells and pathogenesis of SLE. Polymorphisms in these genes are related with the prognostic factors of risk of disease onset and disease severity. The aim of this study was to estimate the influence of polymorphisms in MECP2 and CCR5 genes on the development and course of systemic lupus erythematosus. We examined 137 SLE patients and 604 healthy controls. We studied polymorphisms for CCR5 gene: rs333 and for MECP2: rs2075596, rs1734787, rs17435, and rs2239464. We genotyped our MECP2 samples and we performed a restriction fragment length polymorphism (RFLP) analysis for CCR5 samples. We showed a risk factor for allele T in rs17435 and for allele A in rs2075596 in MECP2. We noticed that MECP2 rs2075596 G/A, rs1734787 C/A, rs17435 A/T, and rs2239464 G/A polymorphisms are more prevalent in SLE patients than in healthy controls. We believe that above-mentioned MECP2 polymorphisms can be considered as SLE susceptibility factor.

Variability of the rs333 in Polish patients with lupus erythematosus

“…This would suggest the role of biogeographic background in the association of the rs333 variability and the susceptibility to SLE. On the other hand, the lack of association was also reported in patients from Poland [ 43 ], Iran [ 44 ] the Netherlands [ 45 ] and Spain [ 46 ]; the observation being consistent with that made in this study. Conversely, the association was revealed in a mixed cohort of patients from Ohio, Colombia and San Antonio (Texas) [ 26 ] as well as in a female sample from Brazil [ 25 ].…”

“…Actually, there are conflicting reports as to how the deletion within the CCR5 gene affects the SLE development. While some studies showed its protective effect for disease propensity [ 18 , 24 ], other reports demonstrated no influence [ 43 – 47 ] or even an increased risk of developing SLE [ 25 , 26 ].…”

Prognostic Impact of Genetic Variants of MECP2 and TIRAP on Clinical Outcomes of Systemic Lupus Erythematosus with and without Nephritis

“…MECP2 reduces the release of IFN-γ by Th cells, producing a partial immune inhibition [ 30 ]. Previous studies revealed a possible genetic association of MECP2 single-nucleotide polymorphisms (SNPs) with susceptibility to SLE [ 23 , 29 , 31 , 32 , 33 , 34 ]; moreover, MECP2 rs2734647 is related to other diseases, such as Rett syndrome [ 35 ], schizophrenia [ 36 ], and aggressive social behavior [ 37 ].…”

“…Doudar et al [ 31 ] found that the A allele of MECP2 rs1734791 is the risk allele for lupus in Egyptian populations. Rzeszotarska et al [ 34 ] stated that rs2075596, rs1734787, rs17435, and rs2239464 within the MECP2 gene are more common in SLE patients than in healthy controls and could possibly constitute predictive elements for the progression and course of SLE in Polish populations. Alesaeidi et al [ 39 ] found that in Iranian patients, rs1734787 and rs1734791 of MECP2 were correlated with SLE progression.…”

“…Bentham et al [ 42 ] announced in their GWAS analysis that MECP2 rs1734787 is an SLE risk factor for people of European ancestry. Rzeszotarska et al [ 34 ] found that variants within the MECP2 gene (rs1734787 and rs2239464) might be related to earlier disease inception and more rapid disease passage and concluded that variants in the MECP2 and CCR5 genes might have an impact on elevated ALT and AST values. Conversely, Doudar et al [ 31 ] did not detect a significant relationship between rs1734791 in MECP2 and disease severity or activity.…”