Originalien
Z Rheumatol 2018 · 77:416–420
https://doi.org/10.1007/s00393-017-0283-7
Published online: 27 February 2017
© Springer-Verlag Berlin Heidelberg 2017
Redaktion
U. Müller-Ladner, Bad Nauheim
U. Lange, Bad Nauheim
I. I. Raafat
1
·N.ElGuindy
1
·R.M.H.Shahin
1
·L.A.Samy
1
·R.M.ElRefai
2
1
Department of Clinical Pathology, Kasr Al Ainy Hospital, Cairo University, Cairo, Egypt
2
Department of Rheumatology and Rehabilitation, Kasr Al Ainy Hospital, Cairo University, Cairo, Egypt
Toll-like receptor 7 gene single
nucleotide polymorphisms and
the risk for systemic lupus
erythematosus: a case-control
study
Introduction
Systemic lupus erythematosus (SLE) is
a polygenic disease that is affected by eth-
nicity, gender, and environmentalfactors.
Toll-likereceptor7(TLR7)hasbeen thor-
oughly studied using lupus-prone mouse
models [1].
e human TLR family consists of
ten receptors classified as members of
the IL-1 receptor (IL-1 R) superfamily
on the basis of a common cytoplasmic
(Toll/IL-1 R) domain. e extracellular
parts of TLRs are diverse, incorporating
varying numbers of leucine-rich repeats.
Following encounter with a ligand, TLRs
elicit a cascade of events leading to the
induction of a number of proinflamma-
tory genes [2]. ese TLR responses are
crucial for the functioning of both the
innate immunity and the adaptive im-
munity [3].
TLRs could respond to both exoge-
nous, microbe-derived pathogen-associ-
ated molecular patterns (PAMPs) and
also endogenous or self ligands. e ca-
pability of TLRs to recognize host-de-
rived danger signals which are produced
on cell necrosis and damage was also
identified [4]. In addition, studies have
found that the immune complexes con-
taining self-DNA and/or self-RNA can
act as endogenous triggers for the acti-
vation of TLRs inducing the expression
The authors have no financial or proprietary
interestin anyproductmentionedinthispaper.
of type I interferon (type I IFN), a cardi-
nal cytokine in the pathogenesis of SLE
[5].
Up-regulated TLR7 mRNA expres-
sion has been detected in peripheral
blood mononuclear cells (PBMCs) from
SLE patients and levels correlate with
the expression of type I IFNs, including
IFN-alpha (IFNα) [6]. Normally, type I
IFNs serve an important function in the
defense against viral infections but in
SLE elevated levels of serum type I IFN is
frequently reported and is of importance
to many aspects of the pathology and
etiology of SLE representing a possible
link between TLR and SLE [7].
Toll-like receptor 7 (TLR7) gene is sit-
uated at Xp22.2 and encodes TLR7 pro-
tein [3]. e association between TLR7
single nucleotide polymorphisms (SNPs)
and SLE could be explained by overpro-
duction of proinflammatory cytokines in
addition to type I IFN [8].
It has now been demonstrated that
miRNAs can act to adjust TLR signaling
by targeting expression itself or by mod-
ulating downstream regulators, adaptor
molecules, and cytokines [9]. Variants
in the 3
′
untranslated region (UTR) of
TLR7 rs3853839 (G/C) may affect miR-
NAs binding and consequently TLR7
expression and/or responsiveness. e
G-allele carriers have increased TLR7
transcripts and are more anticipated
than C-allele carriers to have anti-RNA
associated autoantibodies [10]. e non-
risk C allele has a binding site for mi-
croRNA-3148 (miR-3148) resulting in
a faster breakdown of the transcript and
thus lower levels of TLR7 gene product
[11].
Within this context, this case–control
study was carried out to detect whether
TLR7 rs3853839 and rs179019 SNPs con-
fer risk to SLE in a cohort of Egyptian
female patients and also to explore the
association of the polymorphisms with
various parameters of the disease.
Material and methods
Study subjects
Fiyfemales with SLE,diagnosedaccord-
ing to the 2012 Systemic Lupus Inter-
national Collaborating Clinics (SLICC)
classification criteria, [12] were studied.
eir mean age was 28.8 ± 8.7 years. All
patients were recruited from Rheumatol-
ogy and Rehabilitation Department, Kasr
Al Ainy Hospital Cairo University, and
tenants of declaration of Helsinki were
respected. Disease activity was assessed
with the Systemic Lupus Erythematosus
Disease Activity Index (SLEDAI) [13]. It
includes 24 weighted clinical and labo-
ratory variables of nine organ systems.
erangeofscoresofthedescriptorsis
from 1–8, and the total possible score
for all 24 descriptors is 105. Activity
categories were defined on the basis of
SLEDAI scores: no activity (SLEDAI < 2),
mild activity (SLEDAI = 2–8), moderate
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