Disease relevance of COL9A3

• COL9A3: A third locus for multiple epiphyseal dysplasia [1].
• Recently associations of COL9A2 (Trp2 allele) and COL9A3 (Trp3 allele) polymorphisms with lumbar disc disease characterized by sciatica have been reported [2].
• The novel phenotype of MED and mild myopathy is likely caused by a dominant-negative effect of the exon 3-skipping mutation in the COL9A3 gene [3].
• The present data indicate that mutations of COL9A3 may cause non-syndromic hearing impairment [4].
• OBJECTIVES: To evaluate the interaction between the COL9A3 gene polymorphism and persistent obesity in relation to lumbar disc degeneration [5].

Psychiatry related information on COL9A3

• Patients with autonomic symptoms may have transitory IGT as a concomitant manifestation of life stress; glucose tolerance testing of them appears unwarranted in the absence of other compelling symptoms or a family history of IDD [6].
• Psychologic measures were taken by means of a personality inventory (NVM, Dutch short form of the MMPI), a symptom checklist (SLC-90), and a depression inventory (IDD) [7].
• Within treatments, differences between completers and dropouts in minority status and the prevalence of anxiety disorders were most pronounced in MED [8].

High impact information on COL9A3

• A burgeoning number of antigenic targets of the islet cell autoimmunity in IDD have been identified, and more can be anticipated through improved methods for their identification [9].
• The muscle capillary basement membrane width was increased to a similar extent in the insulin-dependent diabetics (control, 1,781 +/- 46 vs. IDD, 2,287 +/- 144 A, P less than 0.001) and in the Vacor diabetic group (2,320 +/- 149 A, P less than 0.001) [10].
• Genetic linkage to the COL9A3 locus on chromosome 20q13.3 was established with a peak log(10) odds ratio for linkage score of 3.87 for markers D20S93 and D20S164 [3].
• Direct sequencing of genomic DNA confirmed the presence of a splice acceptor mutation in intron 2 of the COL9A3 gene (intervening sequence 2, G-A, -1) only in affected family members [3].
• Type IX collagen is a heterotrimer of pro-alpha chains derived from three distinct genes-COL9A1, COL9A2, and COL9A3 [11].

Chemical compound and disease context of COL9A3

• AR was cocrystallized at pH 5.0 with its cofactor NADP+ and inhibitor IDD 594, a therapeutic candidate for the treatment of diabetic complications [12].

Biological context of COL9A3

• Our results also show that COL9A3, located on chromosome 20, is a third locus for MED [1].
• The Trp3 genotype was determined by means of sequencing the COL9A3 gene [13].
• Physical and linkage mapping of the gene for the alpha3 chain of type IX collagen, COL9A3, to human chromosome 20q13.3 [14].
• In view of recent reports that common single nucleotide polymorphisms in COL9A2 and COL9A3 are linked to chronic sciatica associated with disc pathology, the specific interactions and role of collagen IX in disc tissue are important to define [15].
• Cardiac output and systemic vascular resistances did not differ between patients with IDD and control subjects [16].

Anatomical context of COL9A3

• Intervertebral disc degeneration in relation to the COL9A3 and the IL-1ss gene polymorphisms [2].
• Mutation analysis of COL9A3, a gene highly expressed in the cochlea, in hearing loss patients [4].
• cDNA microarray analysis indicated that COL9A1 and COL9A3 are highly expressed in the human inner ear, suggesting that type IX collagen has a crucial functional role in the inner ear [17].
• Given the complex and multiple physiological functions of islet cells and the continuous variation in their activity, it is reasonable to speculate that the speed of the progression to IDD could vary between individuals with respect to their insulin needs and the relative activities of their islets [9].
• The total weight of the pancreas was markedly decreased in IDD because of an almost selective atrophy of the lobe poor in PP cells; the relative weight of the lobe rich in PP cells was thus much higher than that in control subjects [18].

Associations of COL9A3 with chemical compounds

• OBJECTIVES: To determine the contribution of COL9A2 and COL9A3 Tryptophan polymorphisms to intervertebral disc disease development in a genetically heterogeneous, Southern European population compared to previous Finnish studies [19].
• This study examines the feasibility of deriving the 24-h insulin requirement of insulin-dependent diabetic patients who were devoid of any endogenous insulin release (IDD) from the insulin-production rate (IPR) of healthy man (basal, 17 mU/min; stimulated 1.35 U/12.5 g glucose) [20].
• In neurochemical and electrophysiological correlates of antipsychotic drug action, SSR180711 increased extracellular levels of dopamine in the prefrontal cortex (MED: 1 mg/kg) and enhanced (3 mg/kg) spontaneous firing of retrosplenial cortex neurons in rats [21].
• Two X-ray data sets for a complex of human aldose reductase (h-AR) with the inhibitor IDD 594 and the cofactor NADP(+) were collected from two different parts of the same crystal to a resolution of 0.81 A at 15 and 60 K using cold helium gas as cryogen [22].
• All three variables increased during the arginine infusion in all groups, with the exception that CPR remained unchanged in the IDD [23].

Other interactions of COL9A3

• Type IX collagen is composed of three polypeptides derived from the human genes COL9A1, COL9A2, and COL9A3 that assemble to form a mature collagen molecule with the structure alpha 1(IX)alpha 2(IX)alpha 3(IX) [24].
• The direct-sequencing method was applied to the COL9A3 gene in 159 non-syndromic sensorineural deafness patients and 150 normal controls [4].
• Our studies have identified two susceptibility loci of OA: COL2A1 and COL9A3 [25].

Analytical, diagnostic and therapeutic context of COL9A3

• Molecular cloning of the alpha 3 chain of human type IX collagen: linkage of the gene COL9A3 to chromosome 20q13.3 [24].
• The screening identified a unique change in PCR products of exon 3 of the COL9A3 gene [26].
• cDNA microarray analysis indicated that COL9A3 is one of the highly expressed genes in the cochlea [4].
• Utilizing fluorescence in situ hybridization, radiation hybrid mapping, and multipoint linkage analysis, we have mapped COL9A3 to human chromosome 20q13.3, 13 cM telomeric to D20S173 [14].
• Whereas there is still much to learn, it is clear that disease predictability and disease intervention studies have been enhanced through the identification of the islet cell autoantigens in IDD [9].

References