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Genome‐wide differential expression reveals candidate genes involved in the pathogenesis of lupus and lupus nephritis
Author(s) -
AlFadhli Suad,
Ghanem Aqeel A. M.,
Nizam Rasheeba
Publication year - 2016
Publication title -
international journal of rheumatic diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 41
eISSN - 1756-185X
pISSN - 1756-1841
DOI - 10.1111/1756-185x.12745
Subject(s) - lupus nephritis , systemic lupus erythematosus , candidate gene , pathogenesis , immunology , medicine , gene expression profiling , biology , genetics , gene , gene expression , disease
Background Systemic lupus erythematosus (lupus) is an autoimmune disease characterized by multiorgan pathology, accelerated apoptosis and hyper‐autoantibody production against self‐components. The root cause of lupus remains unknown, although multiple susceptibility factors have been reported in different ethnic group. Objective We aimed to explore the genome‐wide differential expression spectrum of lupus and its severe form lupus nephritis ( LN ) in Arab females. Methods A total of 98 subjects: 40 lupus, 18 LN and 40 age/gender/ethnically matched healthy controls ( HC ) were recruited. Carefully chosen subjects ( n = 11) were employed for whole human‐genome expression profiling using high‐density Human Exon 1.0. ST arrays (Affymetrix) and statistical analysis was carried out using appropriate software. Validation cohorts ( n = 98) were investigated to quantify the expression of the nine selected candidate genes relative to GAPDH as endogenous control. Results Genome‐wide differential analysis revealed seven candidate genes in lupus and 36 in LN , when individually compared to HC ( anova Welch t ‐test, P ≤ 0.005, Tukey's honestly post hoc analysis). Analysis of differentially expressed genes with a fold change of 2, revealed 16 Gene Ontology terms satisfying a P ≤ 0.05. We further detected five distinct inflammatory and metabolic pathways such as TWEAK , osteopontin, endochondral ossification, fluropyrimidine activity and urea cycle and metabolism of amino groups that significantly contribute to the pathogenesis of lupus ( P < 0.05). Validation of selected candidate genes ( IRF 9 , ABCA 1 , APOBEC 3 , CEACAM 3, OSCAR , TNFA 1P6 , MMP 9 , SLC 4A1 ) revealed significant differences in expression, indicating their promissory role in the pathogenesis of lupus. Conclusion Our study provides central gene regulators of therapeutic potential, indicating the future prospects of the study.