OBJECTIVE: @entity785 ( @entity785 ) is a @entity66 attributed to both genetic susceptibility and environmental factors. This study was undertaken to investigate the associations between @entity785 -associated genetic variants and the expression of extracellular matrix (ECM) genes in @entity1 fibroblasts stimulated with @entity3440 particles in time-course and dose-response experiments. METHODS: A total of 200 fibroblast strains were examined for ECM gene expression after stimulation with @entity3440 particles. The fibroblasts were genetically profiled using Immunochip assays and then subjected to whole-genome genotype imputation. Associations of genotypes and gene expression were first analyzed in a Caucasian cohort and then validated in a meta-analysis 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-based longitudinal association test on regions that included the loci identified. RESULTS: The single-nucleotide polymorphism @entity68762 in @entity4639 was consistently associated with time-course and/or dose-response expression of @entity1549 and @entity3334 in the fibroblasts stimulated with @entity3440 particles in both the analysis of Caucasian subjects only and the meta-analysis. Results of the haplotype-based analysis validated the association signals. CONCLUSION: Our findings indicate that a genetic variant of @entity4639 is strongly associated with the @entity3440 -induced profibrotic response of fibroblasts. In silico functional analysis based on the ENCODE database revealed that @entity68762 might affect the binding activities of the transcription factors for @entity4639 . This is the first genome-wide study of interactions between genetic and environmental factors in a complex @entity785 fibroblast model.

Identification of an Association of XXXX Polymorphisms With Matrix Metalloproteinase Expression in Fibroblasts in an Integrative Study of @entity785 -Associated Genetic and Environmental Factors.

@entity1 :: ('9606', 'Species') :: ['human'] @entity3334 :: ('4312', 'Gene') :: ['MMP1'] @entity66 :: ('MESH:D004194', 'Disease') :: ['fibrotic disease'] @entity68762 :: ('rs58905141', 'SNP') :: ['rs58905141'] @entity4639 :: ('7128', 'Gene') :: ['TNFAIP3'] @entity1549 :: ('4314', 'Gene') :: ['MMP3'] @entity3440 :: ('MESH:D012822', 'Chemical') :: ['silica'] @entity785 :: ('MESH:D012595', 'Disease') :: ['Systemic sclerosis', 'SSc']
@entity4639 :: (7128,Gene) :: ['TNFAIP3']
