Abstract
The TGF-β1 cytokine concentration is known to be higher in nephritis with implied Lupus Nephritis severity. The production of TGF-β1 cytokine is associated with G915C polymorphism. Therefore, it is of interest to study G915C polymorphism. The G915C polymorphism changes codon 25 which encodes arginine into proline in the signal peptide of TGF-β1. The amino acid substitution affects signal peptide properties that may inhibit the transport of TGF-β1 into the endoplasmic reticulum and eventually decline the cytokine production. Hence, the effect of G915C polymorphism on the properties of the signal peptide, the ability of TGF-β1 transport into the endoplasmic reticulum and the concentrations of urinary TGF-β1 in Lupus Nephritis patients was studied. The arginine substitution into proline decreased the polarity of the signal peptide for TGF-β1. The increased hydrophobicity with increased binding energy of the signal peptide for TGF-β1 to Signal Recognition Particle (SRP) and translocon is shown. This implies decreased protein complex stability in potentially blocking the transport of TGF-β1 into the endoplasmic reticulum. This transport retention possibly hampers the synthesis and maturation of TGF-β1 leading to decreased cytokine production.
Highlights
The etiology of lupus disease is not yet clearly entirely understood
The docking analysis result suggested that on the signal peptide of TGF-β1 R-25 variant and P-25 variant have different binding pattern when bond to Results: The G915C polymorphism analysis found that none of the subject had CC genotype, and only one subject had GC genotype each in both Lupus Nephritis patients and control groups
The binding stability between a complex of the signal peptide of TGF-β1 with Signal Recognition Particle (SRP)/translocon was analyzed by molecular dynamics simulation (YASARA)
Summary
The etiology of lupus disease is not yet clearly entirely understood. A number of study support that genetic factorThe G915C polymorphism changes codon 25 which encodes arginine into proline of the signal peptide of TGF-β1. The etiology of lupus disease is not yet clearly entirely understood. A number of study support that genetic factor. The G915C polymorphism changes codon 25 which encodes arginine into proline of the signal peptide of TGF-β1. The change from arginine into proline alters the signal peptide plays a role in disease manifestation [1, 2]. Studies focus on the affiliation of genetic polymorphism to lupus susceptibility and severity [1]. Several genetic predispositions to lupus have been investigated, one of which is a cytokine polymorphism [3]. Individuals with homozygote genotype (arginine/arginine) have more concentrations of serum TGF-β1 than those with heterozygote genotype (arginine/proline) [7, 9]. The increasing of effect of G915C polymorphism on the properties of the signal
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