MEFV M694V mutation has a role in susceptibility to ankylosing spondylitis: A meta-analysis

PLOS ONE, Dec 2019

Objective The aim of the current study was to determine the contributions of several common mutations in the Mediterranean fever (MEFV) gene, namely, E148Q, M680I, M694V and V726A, to ankylosing spondylitis (AS) susceptibility. Methods Two investigators independently searched the literature regarding the association of MEFV with AS in the PubMed, EMBASE, Web of Science, and Scopus databases. They independently selected eligible articles and then extracted data from the included studies. The associations between MEFV mutations and AS risk were assessed with odds ratios (ORs) and 95% confidence intervals (95% CI). Further analyses were conducted with STATA 12.0 software (Stata Corp.; College Station, Texas, USA). Results 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.

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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)


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Linqing Zhong, Hongmei Song, Wei Wang, Ji Li, Mingsheng Ma. MEFV M694V mutation has a role in susceptibility to ankylosing spondylitis: A meta-analysis, PLOS ONE, 2017, Volume 12, Issue 8, DOI: 10.1371/journal.pone.0182967