Characterization of a dinucleotide repeat in the 92 kDa type IV collagenase gene (CLG4B), localization of CLG4B to chromosome 20 and the role of CLG4B in aortic aneurysmal disease

Abstract

Proteolytic imbalance may play a role in the pathogenesis of abdominal aortic aneurysms (AAA). CLG4B, which encodes the 92-kDa form of type IV collagenase, is a candidate gene for AAA. We genotyped a polymorphic dinucleotide repeat in the 5' flanking region of CLG4B in 94 unrelated Caucasian controls and in 127 unrelated Caucasian AAA cases. Eight alleles were detected in 188 control chromosomes with an observed heterozygosity of 0.68. There was no significant difference in allele distribution between cases and controls. We genotyped the dinucleotide repeat in 10 CEPH reference pedigrees and performed pairwise linkage analysis with markers on each of the 22 human autosomes. Lod scores between 10.45 and 20.29 were observed with markers spanning chromosome region 20q11.2-q13.1. Further support for assignment of CLG4B to chromosome 20 was provided by analysis of human-rodent somatic cell hybrids. This work describes a highly polymorphic marker in the CLG4B gene and assigns this gene to chromosome 20.

Matrix Metalloproteinase-9 as a Novel Player in Synaptic Plasticity and Schizophrenia: Table 1.

“…Although the etiology of schizophrenia remains largely unknown, it appears to involve interactions between many genes, some of which encode proteins that regulate synaptic plasticity. Notably, chromosome region 20q11-13, where the MMP-9 gene is located, 33 has been extensively studied in terms of psychiatric disorders and linked to schizophrenia. 34 MMP-9 influences hippocampal and prefrontal cortical function 5,7,18,35,36 and is an interesting candidate molecule that is potentially involved in schizophrenia, a condition in which prefrontal cortex impairment is one of the most common pathological findings.…”

Polymorphisms in Matrix Metalloproteinase-1, -3, -9, and -12 Genes in Relation to Subarachnoid Hemorrhage

“…17,21 The multiallelic (CA)n microsatellite polymorphism in the MMP-9 gene has a bimodal distribution of allele frequencies, with the first peak at the (CA) 14 allele (with 14 tandem repeats of CA dinucleotide) and the second peak at the (CA) 21 , (CA) 22 , and (CA) 23 alleles. 31 It has been shown by the reporter gene assays that in fibroblasts (HT1080), an MMP-9 promoter encompassing 14 CA repeats has only 60% of the transcriptional activity of a promoter with 23 repeats. 27 Differences in promoter activity between alleles have also been detected in esophageal carcinoma cells, with a promoter containing 14 CA repeats having only 50% of the activity of a promoter with 21 CA repeats.…”

Polymorphisms in the matrix metalloproteinase-9 promoters and susceptibility to glial tumors in turkey

“…Overexpression of MMP-9 gene can induce degradation of fibrillin, elastin, gelatin, laminin and type IV collagen that makes up the basement membrane of the blood brain barrier (BBB) (9,30). The genetic code of the MMP-9 is on chromosome 20q12.2-13.1 in humans (15). Several single-nucleotide polymorphisms (SNPs) in the MMP-9 coding region resulting in higher expression have been reported in recent years to be associated with different results depending on the target tumor (22,26,29).…”