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Association of functional microsatellites in the human type I collagen alpha2 chain (COL1A2) gene with systemic sclerosis.

Abstract：

:Systemic sclerosis (SSc) or scleroderma is a generalized disorder of connective tissue. The etiology is poorly understood; however, both genetic and environmental factors have been implicated. To investigate the disease-susceptible gene for SSc, we examined the association of the disease with a gene (COL1A2) for type I collagen, which accumulates excessively in the affected organs. The COL1A2 gene containing a specific combination of the two dinucleotide repeats, repeat-haplotype, is involved in the regulation of gene expression. Homozygotes for a 5'-(CA)13CGCACA(CG)6(CA)8 -(GT)12 -3' were found with significantly higher frequency (P = 0.029, relative risk, RR > 6.93) in SSc patients than in controls, and association was prominent (P = 0.0042, RR > 32.0) in the male patients positive for SSc-specific antinuclear antibodies (ANAs). This repeat-haplotype showed the highest stimulative activity for the transcription of the COL1A2 promoter among the reporter gene constructs tested. The results indicate that a portion of the patients having a specific dinucleotide repeat-haplotype homozygously and expressing the ANAs have a significantly higher risk for SSc than those individuals with other combinations of the repeat-haplotypes.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Hata R,Akai J,Kimura A,Ishikawa O,Kuwana M,Shinkai H

doi

10.1006/bbrc.2000.2731

subject

Has Abstract

pub_date

2000-05-27 00:00:00

pages

36-40

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006291X00927311

journal_volume

272

pub_type

杂志文章

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