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A genetic polymorphism in connexin 37 as a prognostic marker for atherosclerotic plaque development.

Abstract：

BACKGROUND AND OBJECTIVES:Atherosclerosis is a multifactorial disease, in part characterized by chronic inflammatory changes in the vessel wall and loss of normal physical and biochemical interactions between endothelial cells and smooth muscle cells. Previous studies [Hu J., Cotgreave IA. J Clin Invest; 99: 1-5] have provided molecular links between inflammation and myoendothelial communication via gap junctions, suggesting that these structures may be important in the development of the atherosclerotic vessel phenotype. In order to strengthen this premise, the aim of the present work was to probe for structural polymorphisms in connexin 37, a gap junctional protein uniquely expressed in endothelial cells, and to assess for potential genotypic segregation in individuals displaying atherosclerotic plaque. METHODS AND RESULTS:Computer-based comparisons of Expressed Sequence Tags (ESTs) predicted a polymorphism in the human gap junctional protein connexin 37 (cx37). The C1019-T mutation results in a proline to serine shift at codon 319 (cx37*1-cx37*2). A Restriction Fragment Length Polymorphism (RFLP) assay, involving the insertion of a novel Drd I cleavage site in the proline variant revealed a statistically significant over-representation of the cx37*1 allele in association with atherosclerotic plaque-bearing individuals (Odds-ratio for the homozygote = 2.38, Chi2 = 7.693, P = 0.006), in comparison to individuals lacking plaque, irrespective of a history of hypertension. CONCLUSIONS:These data suggest that the C1019-T polymorphism in cx37 may provide 'single gene marker', which could be useful in assessing atherosclerotic plaque development, particularly in cardiovascular risk groups such as those with borderline hypertension.

journal_name

J Intern Med

journal_title

Journal of internal medicine

authors

Boerma M,Forsberg L,Van Zeijl L,Morgenstern R,De Faire U,Lemne C,Erlinge D,Thulin T,Hong Y,Cotgreave IA

doi

10.1046/j.1365-2796.1999.00564.x

subject

Has Abstract

pub_date

1999-08-01 00:00:00

pages

211-8

issue

2

eissn

0954-6820

issn

1365-2796

pii

jim564

journal_volume

246

pub_type

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