Disease relevance of COL4A1

• We concluded that mutation of COL4A1 may cause a spectrum of cerebrovascular phenotypes and that persons with COL4A1 mutations may be predisposed to hemorrhage, especially after environmental stress [1].
• Increased expression of COL4A1 and TIMP-1 at the end stage of disease supports the suggestion that expression increases in association with progression of fibrosis and confirms an observation of increased COL4A1 protein expression [2].

High impact information on COL4A1

• Thus, both genes are expressed in a tissue-specific manner, perhaps due to the unique function of the bidirectional promoter for both genes, which is presumably different from that for COL4A1 and COL4A2 [3].
• Four enzymes reveal polymorphisms with COL4A1, and 10 haplotypes have been observed in Caucasoids [4].
• The human type II collagen gene, COL2A1, has been assigned to chromosome 12, the type III gene, COL3A1, to chromosome 2, and one of the type IV genes, COL4A1, to chromosome 13 [5].
• Combining the two cohorts still showed association for the SERPINE1 (combined OR 1.27, 95% CI 1.07-1.50, P=0.004, PAR 6%), FBN2 (combined OR 1.37, 95% CI 1.07-1.75, P=0.01, PAR 3%) and COL4A1 (combined OR 1.22, 95% CI 1.05-1.42, P=0.007, PAR 7%) genes [6].
• However, the COL4A5 gene contains 51 exons, or one less than COL4A1 [7].

Biological context of COL4A1

• Genes encoding the alpha 1(IV) and alpha 2(IV) chains (COL4A1 and COL4A2) both map to human chromosome 13q34 and have been shown to be transcribed from opposite DNA strands using a common bidirectional promoter that allows coordinate regulation of the two chains [8].
• The lack of linkage disequilibrium between COL4A1 and COL4A2 is in agreement with the relatively high recombination that is observed [4].
• The two subunit genes COL4A1 and COL4A2 are found closely linked in the human and murine genomes and are transcribed divergently from a common promoter [9].
• In 5% FCS, corticosteroids increased ECM deposition, involving upregulation of COL4A1 and CTGF mRNA expression [10].
• Their genes COL4A1 and COL4A2 form a transcription unit in which they are arranged head-to-head and connected by a short common promoter region [11].

Anatomical context of COL4A1

• Other candidate collagen genes encoding basement membrane collagen (COL4A1/A2 and COL4A5/A6) were excluded by linkage analysis (13q33-q34 and Xq22), or by sequence (COL4A3) [12].
• In this study, we used dermal fibroblasts from eight normal individuals and nine males with XLAS to test the hypotheses that COL4A5 mutations increase transcription of COL4A1 and suppress transcription of COL4A6 [13].
• Overexpression of VDUP-1 gene in cultured mesangial cells resulted in type IV collagen alpha1 chain (COL4A1) mRNA induction and accumulation of type IV collagen protein [14].

Associations of COL4A1 with chemical compounds

• Also, streptozotocin-induced diabetic mice were shown to overexpress VDUP-1 as well as COL4A1 [14].
• There were two missense mutations of glycine residues predicted to result in abnormal collagen IV assembly, and one mutation predicted to abolish the traditional COL4A1 start codon [15].

Other interactions of COL4A1

• In view of this relationship and the structural similarities between alpha 1(IV) and alpha 3(IV) and between alpha 2(IV) and alpha 4(IV), we hypothesized that COL4A3 and COL4A4, the genes encoding alpha 3(IV) and alpha 4(IV), respectively, have a genomic organization similar to that of COL4A1 and COL4A2.(ABSTRACT TRUNCATED AT 250 WORDS)[8]
• Immunohistochemical analysis of the strial vessels revealed an increase in entactin and collagen COL4A1 and COL4A2 chains [16].

Analytical, diagnostic and therapeutic context of COL4A1

• We have used pulsed field gel electrophoresis and cloned COL4A1 and COL4A2 DNA fragments as molecular probes to construct a 1200-kb macrorestriction map which encompasses both genes [17].

References