STAT4 gene polymorphism in two major autoimmune diseases (multiple sclerosis and juvenile onset systemic lupus erythematosus) and its relation to disease severity

Rania S Nageeb,Yassir A A Mohammad,Amal Fawzy,Alaa A Omran,Ghada S Nageeb,Manal A Yousef

doi:10.1186/s41983-018-0011-5

Abstract

BackgroundMultiple sclerosis (MS) and systemic lupus erythematosus (SLE) are chronic autoimmune mediated diseases with strong genetic and environmental components. The aim of this study is to evaluate the association of STAT4 gene polymorphism with multiple sclerosis (MS) and juvenile onset systemic lupus erythematosus (JO-SLE) and its relation to disease severity.MethodsGroup 1 consisted of 40 MS patients while group 2 included 40 JO-SLE patients. Forty healthy volunteers (controls) were included in this study. STAT4 genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).ResultsThe STAT4 CC genotype and GC genotype frequencies were significantly more detected in MS and JO-SLE patients than in controls. The frequency of the STAT4 C allele was significantly higher in patients with MS and those with JSLE compared to controls. Malar rash, photosensitivity, and hair falling were significantly more detected in CC subtype. Malar rash, photosensitivity, and hair falling were significantly more detected in CC subtype. Increased 24-h protein in urine (mg/24 h) and ANA positivity, anti-ds-DNA, anti Sm antibodies’ detection and decreased C3 and C4 levels showed a significantly difference in CC patients. Meanwhile, only increased 24-h protein in urine (mg/24 h) and ANA positivity were significantly more detected in GC patients. STAT4 CC genotype showed a significant increase in the SLE activity index (SLEAI) score and damage index as compared to the STAT4 GG genotype patients. No significant difference was detected in MS Kurtzke’s Expanded Disability Status Scale (EDSS) comparing different STATE 4 genotypes.ConclusionsSTAT4 polymorphism was significantly associated with MS and JO-SLE. Though homozygous JO-SLE patients are more risky for severe disease manifestations, homozygous MS patients are not risky for severe disease disability.

Highlights

Multiple sclerosis (MS) and systemic lupus erythematosus (SLE) are chronic autoimmune mediated diseases with strong genetic and environmental components
In the current study. 11 (27.5%) MS patients presented with progressive course and 29 (72.5%) patients with relapsing remittent (RR) MS with mean Expanded Disability Status Scale (EDSS) score of patients was 4.76 ± 2.65
The Signal transducer and activator of transcription (STAT) 4 CC genotype and GC genotype frequencies were significantly more detected in MS and juvenile onset systemic lupus erythematosus (JO-SLE) patients than in controls (p = 0.01 and 0.05 and p = 0.001 and 0.01 for both respectively)

Summary

Introduction

Multiple sclerosis (MS) and systemic lupus erythematosus (SLE) are chronic autoimmune mediated diseases with strong genetic and environmental components. The aim of this study is to evaluate the association of STAT4 gene polymorphism with multiple sclerosis (MS) and juvenile onset systemic lupus erythematosus (JO-SLE) and its relation to disease severity. Multiple sclerosis (MS) and systemic lupus erythematosus (SLE) are chronic autoimmune diseases with strong genetic and environmental components. They can be triggered by various environmental components, such as exposure to ultraviolet light, drugs, chemicals, and viral infections. The human STAT (signal transducer and activator of transcription) genes have been identified in three chromosomal clusters: STAT1 and STAT4 on human chromosome 2 (q12-33); STAT2 and STAT6 on chromosome 12 (q13-14); and STAT3, STAT5a, and 5b on chromosome 17 (q11.2-22). STAT4 is essential for IL-12 signaling and induces interferon-gamma (IFNγ) production (Gestermann et al 2010)

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