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This gene encodes the major component of type I collagen, the fibrillar collagen found in most connective tissues, and the only component of the collagen found in cartilage. Mutations in this gene are associated with osteogenesis imperfecta, Ehlers-Danlos syndrome, and idiopathic osteoporosis. Reciprocal translocations between chromosomes 17 and 22, where this gene and the gene for platelet-derived growth factor beta are located, are associated with a particular type of skin tumor called dermatofibrosarcoma protuberans, resulting from unregulated expression of the growth factor. Two transcripts, resulting from the use of alternate polyadenylation signals, have been identified for this gene. A 30-residue peptide model of the alpha 1(I) chain of type I collagen is designed which demonstrates sequence preference of the C-terminal repeating (Gly-Pro-Hyp)4 subdomain for initiation of triple-helix formation--an all-or-none third-order reaction. A degradation fragment originating from the helical part of type I collagen consisting of residues 620-633 of the alpha 1 chain sequence is useful clinically as a bone resorption marker in patients with osteoporosis. A fusion of COLIA1 exon 24 in frame with PDGFB exon 2 was found in a complex marker chromosome from dermatofibrosarcoma protuberans with sequences from chromosomes 7,8,17,21, & 22. A member of the Y-box protein family interacts with an upstream element in the alpha1(I) collagen gene. Allele frequency of the G-->T mutation of this gene is analyzed by an ARMS-PCR in osteoporotic subjects with femoral neck fractures. Although connective tissue growth factor alone had no effect on collagen secretion, combined stimulation with IGF-I enhanced collagen accumulation. Analysis of the Collal alleles provides early detection of the individuals with hereditary predisposition to osteoporosis and prophylaxis of the disease at the presymptomatic stage. C-propeptide region of human pro alpha 1 type 1 collagen interacts with thioredoxin. CIITA induction is required for interferon gamma-mediated repression of COL1A1 and COL1A2. COL1A1 gene expression is downregulated by B-Myb in fibroblasts from patients with systemic sclerosis. COL1A1 gene may have some effects on bone size variation at the wrist, but not at the spine or hip in Caucasian nuclear families. COL7A1 mutation is characteristic in patients with dystrophic epidermolysis bullosa. COLIA1 Sp1 TT genotype is associated with an increased fracture risk in postmenopausal women. COLIA1 genotype may affect bone accrual in a population treated for childhood cancer. Deletions and duplications of Gly-Xaa-Yaa triplet repeats in the triple helical domains of type I collagen chains disrupt helix formation and result in several types of osteogenesis imperfecta. Fusion of COL1A1 exon 29 with PDGFB exon 2 in a der(22)t(17;22) in a pediatric giant cell fibroblastoma with a pigmented Bednar tumor component. Evidence for age-related chromosomal pattern in dermatofibrosarcoma protuberans and related tumors. In a cohort of 75-year-old Swedish women, there was an association among the Sp1 COLIA1 polymorphism, bone mass, and fracture. Interaction of human breast fibroblasts with collagen I increases total cathepsin B protein levels. Osteogenesis imperfecta Type 1: diagnosis could be verified by moleculargenetic analysis, a newly recognized heterozygous point mutation (Arg420Stop) in the COL1A1-gene was found. Polymorphism analysis in the COLIA1 gene of patients with thalassemia major and intermedia. Predicted rates of AA substitution for Gly were compared with missense mutations known to cause disease. The most destabilizing residues, Val, Glu, & Asp, & the least destabilizing residue, Ala, were underrepresented. Results characterize promoters from the human alpha1(I) procollagen gene. The ""s"" allele of COLIA1 gene in combination with the Px haplotype of the ER alpha gene contributes to reduced BMD in females. The COL1A1 polymorphism is independently associated with bone density in postmenopausal Spanish women. The COLIA1 polymorphism in children and young adults is associated with several bone characteristics. The Sp1 transcription factor binding site polymorphism of COL1A1 is associated with a modest reduction in bone mineral density and a significant increase in risk of osteoporotic fracture, particularly vertebral fracture. The collagen type I, alpha 1 polymorphism in the Sp1 binding site is associated with differences in ultrasound transmission velocity in the calcaneus of postmenopausal women. The effect of the COLIA1 Sp1 polymorphism and ultrasound velocity on wrist fracture risk is more pronounced in patients with a higher body weight. The genotype frequency of COLIA1 polymorphism was also not different between PBC patients and controls, however the ""s"" allele was significantly less frequent in patients with PBC (p = 0.038). The lower collagen content in the endopelvic fascia and skin of women with SUI is not due to reduced collagen synthesis or selective reduction in synthesis of either collagen I or collagen III. These data indicate that mitoxantrone and WP631 are very potent inhibitors of basal and TGF-beta-stimulated COL1A1 expression. This is the first molecular modeling study addressing type I collagen alpha 1 chain carboxyl (C)-telopeptide conformation using all three chains of the heterotrimer before and after it docks to its receptor domain. This protein is regulated by human basic fibroblast growth factor. This study identified a novel COL1A1 breakpoint, namely, exon 42 of the COL1A1 gene. This study showed a significant association between otosclerosis and the COL1A1 first intron Sp1 site. The allelic frequency of the Sp1 site is very similar between otosclerosis and osteoporosis. Upstream elements present in the 3'-untranslated region of the gene influence the processing efficiency of overlapping polyadenylation signals. We concluded that huCI is a novel substrate protein of PADIs and that citrullinated huCI is a candidate autoantigen of RA. Disulfide disruption permits slow assembly and secretion of overmodified, but stable procollagen trimers and results in mild osteogenesis imperfecta. Estrogen receptor alpha Px haplotype and collagen IA1 s allele may be involved in causing the phenotypic expression of higher circulating levels of parathyroid hormone and higher bone turnover, which may lead to bone loss. Genetic polymorphisms of the vitamin D receptor, estrogen receptor, and collagen Ialpha1 genes were characterized in 72 osteosarcoma and 53 Ewing sarcomas and in a group of 143 healthy matched children. HnRNPE1, and K are positive effectors of collagen synthesis acting at the post-transcriptional level by interaction with the 3'-untranslated region (3'-UTR) of COL1A1 mRNAs. In men, the ""ss"" genotype of COLIA1 polymorphism could be the best osteoporotic fracture risk genetic predictor, independent of bone mass values. In the presence of high molecular weight fragments of type I collagen, type I procollagen synthesis is inhibited. Investigation of the genetic influence of the Sp1 polymorphism on bone density in Irish women. Keratinocyte growth factor (KGF), a key stimulator of epithelial cell proliferation during wound healing, preferentially binds to collagens I, III, and VI. Mutational analysis in Lithuanian patients with osteogenesis imperfecta. Mutations near amino end of alpha1(I) collagen are directly responsible for the bone fragility of osteogenesis imperfecta and indirectly responsible for Ehlers-Danlos syndrome symptoms, by interference with N-propeptide removal. Prostate carcinoma cell proliferation is enhanced by the down-regulation of BRCA2 expression when interacting with COL1, a major component of the ECM at osseous metastatic sites. The common genetic variants at the PCOL2 and Sp1 sites, and importantly, their interactive effects, may contribute to bone mineral density variation in elderly Caucasian females. Two new SNPs in the COL1A1 promoter, which may affect bone mass determination.
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