Functional Promoter Variant in Zinc Finger Protein 202 Predicts Severe Atherosclerosis and Ischemic Heart Disease
Maria C.A. Stene, MSc, PhD*,
Ruth Frikke-Schmidt, MD, PhD*,
Børge G. Nordestgaard, MD, DMSc , ,
Peer Grande, MD, DMSc ,
Peter Schnohr, MD and
Anne Tybjærg-Hansen, MD, DMSc*,,*
* Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
Department of Clinical Biochemistry, Herlev University Hospital, Copenhagen, Denmark
Copenhagen City Heart Study, Bispebjerg University Hospital; all Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
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Figure 1 Pairwise Linkage Disequilibrium Between 9 SNPs in the Promoter and Coding Region of ZNF202 Genotyped in CCHS (n = 8,942)
Disequilibrium statistics reported as D', ranging from –1 to +1, below the black diagonal, and r2, ranging from 0 to 1, above the black diagonal. For D', plus indicates that the rare alleles at each locus segregate together; minus indicates that the rare allele at 1 locus segregates with the common allele at the other locus. g.–685G>A=rs10726530; g.–660A>G=rs10893081; g.–118G>T not reported; g.+34G>A=rs2272142; c.IVS4–240A>T=rs2282641; c.IVS4–223T>C=rs2282642; p.A154V(c.461C>T)=rs1144507; p.K259E(c.775A>G) not reported, c.*2T>G=rs3183878. CCHS = Copenhagen City Heart Study; IVS = intervening sequence; rs = reference single nucleotide polymorphism; SNP = single nucleotide polymorphism.
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Figure 3 Risk of IHD, MI, and Angina Pectoris as a Function of ZNF202 g.–660A>G Genotype
Age adjusted hazard ratios (prospective study, left panels) or odds ratios (case-control studies 1 and 2, middle and right panels) with 95% confidence intervals for ischemic heart disease (IHD) (upper panels), for myocardial infarction (MI) (middle panels), and for angina pectoris (lower panels) as a function of ZNF202 g.–660A>G genotype in the general population. The AA genotype is the reference group. Prospective study (left panels): n = 1,511 incident cases with IHD, including, respectively, 749 and 762 incident cases with MI or angina pectoris; case-control study 1 (middle panels): n = 942 cases with IHD, including, respectively, 491 and 451 cases with MI or angina pectoris; case-control study 2 (left panels): n = 1,549 cases with IHD, including, respectively, 644 and 905 cases with MI and angina pectoris.
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Figure 4 ZNF202 Promoter Expression Studies as a Function of g.–660A>G Genotype
HepG2 cells were transfected with the pG13 basic vector containing 834 base pairs (–710 to +124) of the ZNF202 promoter with either A or G at position g.–660. Three separate experiments were performed in triplicate, each with 2 different DNA preparations. Results are expressed as relative luciferase activity (means ± SD). The p values were determined by Mann-Whitney U test.
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0.7. (B) 4,405 individuals with an ABI >0.9 (reference group) were compared with 229 individuals with an ABI