• ITRI Biotechnology Forum, 2003 

 

Shih-chang Sun, Shuenn-Nan Chiu, Mei-Hwan Wu and Min-Yuan Chou

Department of Applied Gene Technology (H300), Biomedical Engineering Center,

Department of Pediatrics, National Twain University Hospital

 

ABSTRACT

The human a1-chain of type XXI collagen (COL21A1) is an extracellular matrix component of the blood vessel walls. Our previous study showed that the expression of COL21A1 in human tissues is developmentally regulated, suggesting that the collagen type 21 may contribute to the extracellular matrix assembly of the vascular network during blood vessel formation. It is attractive to speculate that the COL21A1 gene mutation may cause dysfunction in blood vessel assembly during arteriogenesis. In this study, we analyzed the COL21A1 gene polymorphism from 105 patients with congenital cardiovascular diseases and 25 healthy individuals in Taiwan. We have identified a single nucleotide polymorphism (SNP), C1208T, located in the exon 6 of COL21A1. Allele frequencies for both groups were 94.2% C and 5.8% T. There is no significant difference in allele frequencies of the C1208T SNP between the patient and healthy populations. The C1208T SNP results in a single amino acid change from threonine to methionine at codon 343, which is located in the thrombospodin N-terminal like (TSPN) domain of a1(XXI) collagen. Interestingly, this region has been reported to be involved in glycosaminoglycan (GAG) binding. We plan to use heparin binding assay to investigate whether T343M alteration in the TSPN domain of al(XXI) collagen influences GAG binding affinity. Meanwhile, short tandem repeat polymorphism analysis of the eight CA-dinucleotide repeats in COL21A1 is in progress. We hope to find novel polymorphisms in the COL21A1 gene that may be related to congenital cardiovascular disorders and this will help us to develop genetic markers for clinical diagnosis.