{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T03:41:08Z","timestamp":1789184468292,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,2,24]],"date-time":"2016-02-24T00:00:00Z","timestamp":1456272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Department of the Army, Medical Research Acquisition Activity","award":["PR064803"],"award-info":[{"award-number":["PR064803"]}]},{"DOI":"10.13039\/100001844","name":"Scleroderma Foundation","doi-asserted-by":"crossref","award":["2012"],"award-info":[{"award-number":["2012"]}],"id":[{"id":"10.13039\/100001844","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH","award":["U01"],"award-info":[{"award-number":["U01"]}]},{"name":"NIH","award":["1U01-AI-09090"],"award-info":[{"award-number":["1U01-AI-09090"]}]},{"name":"NIH","award":["R01-CA-169122"],"award-info":[{"award-number":["R01-CA-169122"]}]},{"name":"NIH","award":["R01-HL-116720"],"award-info":[{"award-number":["R01-HL-116720"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Systemic sclerosis (SSc) is a fibrotic disease attributed to both genetic susceptibility and environmental factors. This study was undertaken to investigate the associations between SSc\u2010associated genetic variants and the expression of extracellular matrix (ECM) genes in human fibroblasts stimulated with silica particles in time\u2010course and dose\u2010response experiments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 200 fibroblast strains were examined for ECM gene expression after stimulation with silica particles. The fibroblasts were genetically profiled using Immunochip assays and then subjected to whole\u2010genome genotype imputation. Associations of genotypes and gene expression were first analyzed in a Caucasian cohort and then validated in a meta\u2010analysis combining the results from Caucasian, African American, and Hispanic subjects. A linear mixed model for longitudinal data analysis was used to identify genetic variants associated with the expression of ECM genes, and the associations were validated by using a haplotype\u2010based longitudinal association test on regions that included the loci identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The single\u2010nucleotide polymorphism rs58905141 in <jats:italic>TNFAIP3<\/jats:italic> was consistently associated with time\u2010course and\/or dose\u2010response expression of <jats:italic>MMP3<\/jats:italic> and <jats:italic>MMP1<\/jats:italic> in the fibroblasts stimulated with silica particles in both the analysis of Caucasian subjects only and the meta\u2010analysis. Results of the haplotype\u2010based analysis validated the association signals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings indicate that a genetic variant of <jats:italic>TNFAIP3<\/jats:italic> is strongly associated with the silica\u2010induced profibrotic response of fibroblasts. In silico functional analysis based on the ENCODE database revealed that rs58905141 might affect the binding activities of the transcription factors for <jats:italic>TNFAIP3<\/jats:italic>. This is the first genome\u2010wide study of interactions between genetic and environmental factors in a complex SSc fibroblast model.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39476","type":"journal-article","created":{"date-parts":[[2015,10,16]],"date-time":"2015-10-16T16:04:51Z","timestamp":1445011491000},"page":"749-760","source":"Crossref","is-referenced-by-count":29,"title":["Identification of an Association of <i>TNFAIP3<\/i> Polymorphisms With Matrix Metalloproteinase Expression in Fibroblasts in an Integrative Study of Systemic Sclerosis\u2013Associated Genetic and Environmental Factors"],"prefix":"10.1002","volume":"68","author":[{"given":"Peng","family":"Wei","sequence":"first","affiliation":[{"name":"University of Texas Health Science Center at Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at 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