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Assessment of novel biochemical and genetic markers for outcomes of coronary artery disease in an angiographically defined patient population

University of British Columbia

We have studied the relationship between inflammatory markers (C-reactive protein {CRP}, IL-6, and serum amyloid A protein {SAA}) and a single nucleotide polymorphism (SNP) of C-reactive protein at position 1059G/C and coronary atherosclerosis, in 1,039 patients (537 patients for SNP study) who underwent selective coronary angiography (SCA) in 1993-95. SCA findings, clinical and lifestyle variables, serum lipids, atherosclerosis morbidity from 7-10 yr follow-up, and mortality at 4-5 yr. follow up were correlated with inflammatory and genetic markers. We hypothesized that the levels of inflammatory markers and CRP 1059G/C polymorphism will be correlated with coronary artery disease (CAD) presence, severity, and outcomes of morbidity and mortality. In univariate analyses, CRP levels were associated with CAD presence, and CRP and IL- 6 levels were associated with CAD severity. However, SAA showed no association with angiography findings. None of the inflammatory markers correlated with atherosclerosis related morbidity or CAD outcomes. However, all three inflammatory markers were independent predictors of mortality. The frequencies of the CRP 1059 allele did not differ between the CAD-ve and CAD+ve groups (Chi-sq test, P=0.976). However, the levels of CRP were significantly different in the 1059G and 1059C groups, respective geometric means (1.89 vs. 1.25 mg/L, P=0.006). In conclusion, serum levels of inflammatory markers (CRP, SAA, and IL-6) were independent predictors of CAD severity arid mortality but not morbidity. CRP SNP 1059G/C was an independent modulator of CRP levels but it was not a predictor of CAD in this population. In addition to studying the association between inflammatory markers and CAD, relationship between APOA5 gene, which has been shown to be associated with triglyceride levels in several independent population studies, and CAD was investigated. It was our objective to determine if a relationship existed between a single nucleotide polymorphism of the APOA5 gene and findings on selective coronary angiography (SCA) in an independent cohort. DNA of 537 random patients from the Vancouver SCA cohort was analyzed for the - 1131 T>C polymorphism (SNP 3) of the APOA5 gene. The minor allele (-1131C) frequency was 8% in the Caucasian population and 24% in the Asian population. Plasma triglycerides and the fractional esterification rate in apoB-depleted lipoproteins (FER[sub HDL]), an index of HDL composition, were significantly higher (P=0.021 and P=0.002, respectively), and HDL-C was significantly lower (P=0.044) in Caucasians with genotypes containing the minor allele compared to the homozygotes for the major allele. However, there was no relationship between APOA5 SNP3 and either the presence or severity of coronary artery disease (P=0.619 and P=0.492, respectively). In conclusion, the minor allele of APOA5 SNP3 is associated with increased levels of triglyceride and FER[sub HDL] and decreased levels of HDL-C, but it is not associated with findings on selective coronary angiography in this cohort.

Thesis/Dissertation

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2009-11-03

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http://hdl.handle.net/2429/14605

Pathology

University of British Columbia

UBCV

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