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

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 polymorphic dinucleotide repeat in the 5' flanking region of CLG4B in 94 unrelated Caucasian controls and in 127 unrelated Caucasian AAA cases. Eight al leles were detected in 188 control chromosomes with an observed hetero zygosity of 0.68. There was no significant difference in allele distri bution between cases and controls. We genotyped the dinucleotide repea t in 10 CEPH reference pedigrees and performed pairwise linkage analys is 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 2 0 was provided by analysis of human-rodent somatic cell hybrids. This work describes a highly polymorphic marker in the CLG4B gene and assig ns this gene to chromosome 20.