Archiv - Juni 2010

ANRIL Expression Is Associated With Atherosclerosis Risk at Chromosome 9p21

Holdt LM, Beutner F, Scholz M, Gielen S, Gäbel G, Bergert H, Schuler G, Thiery J, Teupser D

Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Liebigstr. 27, 04103 Leipzig, Germany.

Arterioscler Thromb Vasc Biol. 2010 Mar;30(3):620-7. Epub 2010 Jan 7

Objective— We tested the hypothesis that expression of transcripts adjacent to the chromosome 9p21 (Chr9p21) locus of coronary artery disease was affected by the genotype at this locus and associated with atherosclerosis risk.

Methods and Results— We replicated the locus for coronary artery disease (P=0.007; OR=1.28) and other manifestations of atherosclerosis such as carotid plaque (P=0.003; OR=1.31) in the Leipzig Heart Study, a cohort of 1134 patients with varying degree of angiographically assessed coronary artery disease. Expression analysis in peripheral blood mononuclear cells (n=1098) revealed that transcripts EU741058 and NR_003529 of antisense noncoding RNA in the INK4 locus (ANRIL) were significantly increased in carriers of the risk haplotype (P=2.1x10–12 and P=1.6x10–5, respectively). In contrast, transcript DQ485454 remained unaffected, suggesting differential expression of ANRIL transcripts at Chr9p21. Results were replicated in whole blood (n=769) and atherosclerotic plaque tissue (n=41). Moreover, expression of ANRIL transcripts was directly correlated with severity of atherosclerosis (EU741058 and NR_003529; P=0.02 and P=0.001, respectively). No consistent association of Chr9p21 or atherosclerosis was found with expression of other genes such as CDKN2A, CDKN2B, C9orf53, and MTAP.

Conclusion— Our data provide robust evidence for an association of ANRIL but not CDKN2A, CDKN2B, C9orf53, and MTAP, with atherosclerosis and Chr9p21 genotype in a large cohort.

Expression analysis in patients of the Leipzig Heart study (n=1098) revealed that antisense noncoding RNA in the INK4 locus (ANRIL) was differentially regulated at the Chr9p21 locus of CAD. In addition, ANRIL expression was correlated with atherosclerosis severity. In contrast, other genes adjacent to the locus remained unchanged.

Link zum Volltext