MEFV M694V mutation has a role in susceptibility to ankylosing spondylitis: A meta-analysis
August
MEFV M694V mutation has a role in susceptibility to ankylosing spondylitis: A meta-analysis
Linqing Zhong 0 1
Hongmei Song 0 1
Wei Wang 0 1
Ji Li 0 1
Mingsheng Ma 0 1
0 Editor: James T. Rosenbaum, Oregon Health and Science University , UNITED STATES
1 Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
Four mutations (E148Q, M680I, M694V and V726A) were genotyped in 869 AS cases and
879 controls from the 8 eligible studies. Of the four mutations, M694V (pooled OR: 3.330,
95% CI: 2.129±5.208) was found to be associated with AS through overall analysis.
However, the other mutations demonstrated no relation with AS (pooled ORs: 1.295, 1.258,
1.778; 95% CI: 0.886±1.891, 0.688±2.298 and 0.938±3.371). No significant publication bias
was discovered in the meta-analysis.
Conclusions
The present study indicates that the MEFV M694V mutation may contribute to the pathogenesis of AS. The associations between the other mutations and AS need to be validated with more relevant and well-designed studies.
The aim of the current study was to determine the contributions of several common muta
tions in the Mediterranean fever (MEFV) gene, namely, E148Q, M680I, M694V and V726A,
to ankylosing spondylitis (AS) susceptibility.
OPEN ACCESS
Objective
Methods
Results
F, AtaguÈnduÈz P. Frequency and disease severity of
familial mediterranean fever (FMF) related MEFV
gene mutations among ankylosing spondylitis
patients. Turkiye Klinikleri Journal of Medical
Sciences. 2014;34(2):223-30.
Funding: This study was supported by grants from
Public Welfare Scientific Research Project of China
(grant number 201402012) and CAMS Central
Public Welfare Scientific Research Institute Basal
Research Expenses to HW (grant number
2016ZX310182-1).The funders had no roles in
study design, data collection and analysis,decision
to publish,or preparation of the manuscript.
Introduction
Ankylosing spondylitis (AS) is a chronic inflammatory disease involving the axial skeleton,
and its main clinical manifestations are back pain and progressive stiffness of the spine. AS
typically develops in young adults with a peak age of onset between 20 and 30 years. Many AS
patients have poor outcomes, and they may gradually progress to spinal fusion with
hyperkyphosis. Patients develop work disability [
1
] and an impaired quality of life (QoL) [
2
] and are
also at a high risk of adverse events such as spinal fracture [
3
]. The mean prevalence of AS is
relatively high all over the world, ranging from 7.4 to 31.9 per 10,000 [
4
]. Estimates of the
prevalence of ankylosing spondylitis in the United States even reach 0.5% [
5
]. Moreover, AS has
significant economic implications for individuals and society [6±8]. Therefore, it is urgent to
study the pathogenesis and treatment of ankylosing spondylitis. However, the pathogenesis of
ankylosing spondylitis is inconclusive. Genetic influences are considered particularly
important in the pathogenesis of AS. The human leukocyte antigen (HLA)-B27 has been regarded as
a dominant susceptibility gene for ankylosing spondylitis [
9, 10
], but HLA-B27 positivity is
relatively low in some conditions [11±13]. Furthermore, only a few of the patients who are
positive for HLA-B27 develop AS [
14, 15
]. With the deepening of cognition, there have been an
increasing number of studies concerning the influence of non-HLA genes, including IL-23R,
IL-1, IL12-B, TNF-α, ERAP1, etc. [16±22].
The Mediterranean fever (MEFV) gene is located on the short arm of chromosome 16 and
is known to be responsible for familial Mediterranean fever (FMF). FMF is a hereditary
autoinflammatory disorder that is characterized by recurrent episodes of fever and serositis.
Enthesopathy and sacroiliitis occur in some FMF patients [23±25], and up to 7.5% of FMF patients
are simultaneously diagnosed with AS [
26
]. Furthermore, linkage has been observed between
the AS bath ankylosing spondylitis disease activity index (BASDAI) and chromosome 16p in a
whole-genome linkage scan [
27
]. Thus, several studies have investigated the association
between AS and the most common mutations of MEFV, but the conclusions are uncertain and
controversial. The aim of the present study was to comprehensively observe the contribution
of several common mutations in the MEFV gene, namely, E148Q, M680I, M694V and V726A,
to ankylosing spondylitis susceptibility.
Materials and methods
Data sources
A comprehensive literature search was performed in the PubMed, EMBASE, Web of Science,
and Scopus databases up to the date of December 31, 2016. Full text searches were used in the
PubMed, EMBASE and Scopus databases, while a medical subject headings (MeSH) search
was applied in the Web of Science database. The keywords were ªankylosing spondylitisº and
ªMEFVº. No restrictions were imposed on the type of studies. The study selection process is
illustrated in (...truncated)