Comparison of various lipid, lipoprotein, and bilirubin combinations as risk factors for predicting coronary artery disease

Schwertner, Harvey A.; Fischer, Joseph

doi:10.1016/s0021-9150(99)00387-1

Cited by 58 publications

(42 citation statements)

References 20 publications

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“…Also, many reports supported a reverse association between bilirubin and CAD [4][5][6][7]. In this study, the levels of bilirubin for the CAD patients were significantly lower than for the participants in the control group.…”

Section: Discussionsupporting

confidence: 57%

“…There was a racial variability in the polymorphisms of the UGT1A1 gene. Asians have a lower frequency of the A (TA) 7 TA allele than Caucasians [16][17][18]. However, Tab.…”

Section: Introductionmentioning

confidence: 95%

“…It was reported that bilirubin inhibits complement-dependent inflammation in vitro [3]. Several clinical epidemiological studies demonstrated the reverse relationship between the serum bilirubin level and coronary artery disease [4][5][6][7][8][9]. It was observed that decreased levels of bilirubin were only associated with coronary artery disease (CAD) in men [10,11].…”

Section: Introductionmentioning

confidence: 99%

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Polymorphisms of the uridine-diphosphoglucuronosyltransferase 1A1 gene and coronary artery disease

Hsieh

Chen

Liao

et al. 2008

Cellular and Molecular Biology Letters

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Abstract:Bilirubin, an antioxidant in the blood, plays a role in protection from atherosclerosis. The level of bilirubin is highly correlated to the incidence of coronary artery disease (CAD). Unconjugated bilirubin is conjugated with glucuronic acid through the reaction of uridine 5'-diphosphate-glucuronosyl transferase 1A1 (UGT1A1). The interactions of CAD and the variations in the coding regions of the UGT1A1 gene have never been evaluated. The purpose of this study was to analyze the influence of the UGT1A1 variant on the incidence of CAD. There were 135 participants in this study: 61 in the experimental group, who had CAD, and 74 in the control group, who did not have CAD. The blood samples from all 135 participants were collected and assayed to clarify the relationship between bilirubin and CAD. The assay of the polymerase chain reaction and the sequence of the UGT1A1 gene were examined to find the gene's polymorphisms. The bilirubin levels for the participants in the control group were significantly higher than for the patients in the CAD group. Although the concentration of bilirubin in the UGT1A1 variant was higher than the wild type for the patients in the CAD group, there was no significant difference in the polymorphism of UGT1A1 between the patients in the CAD group and the participants in the control group.

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Section: Discussionsupporting

confidence: 57%

“…There was a racial variability in the polymorphisms of the UGT1A1 gene. Asians have a lower frequency of the A (TA) 7 TA allele than Caucasians [16][17][18]. However, Tab.…”

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Polymorphisms of the uridine-diphosphoglucuronosyltransferase 1A1 gene and coronary artery disease

Hsieh

Chen

Liao

et al. 2008

Cellular and Molecular Biology Letters

View full text Add to dashboard Cite

show abstract

“…Studies on the relationship between bilirubin concentration and cardiovascular disease have shown an inverse relationship between bilirubin concentration and atherosclerosis (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Low bilirubin concentrations have also been independently and inversely related to impaired flow-mediated vasodilatation and increased carotid intima-media thickness in clinically healthy subjects (14,15 ).…”

confidence: 99%

Association between the UGT1A1 TA-Repeat Polymorphism and Bilirubin Concentration in Patients with Intermittent Claudication: Results from the CAVASIC Study

et al. 2008

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Background: Bilirubin has antioxidative and cytoprotective properties. Low plasma concentrations of bilirubin are reportedly associated with the development of coronary and cerebrovascular disease, and bilirubin concentrations are strongly correlated with the enzyme activity of the hepatic uridine diphosphate glucuronosyltransferase (UGT1A1). The activity of UGT1A1 is influenced by a TA-repeat polymorphism in the promoter of the UGT1A1 gene (UDP glucuronosyltransferase 1 family, polypeptide A1). In a case-control study, we investigated the association between the UGT1A1 polymorphism, bilirubin concentration, and intermittent claudication. Methods: We included 255 consecutive male patients presenting with intermittent claudication in the investigation and matched the patients by age and diabetes mellitus with 255 control individuals. Results: Plasma bilirubin concentrations were significantly lower in patients than in controls [mean (SD), 12.5 (5.3) μmol/L vs 15.4 (7.9) μmol/L; P < 0.001]. We found a clear association between the number of TA repeats and plasma bilirubin concentration. Considering the 6/6 TA-repeat genotype as the wild type, we observed a slight increase in bilirubin concentration individuals with the heterozygous 6/7 genotype and pronounced increases for those with the homozygous 7/7 genotype. This association occurred in both controls and patients; however, patients and controls were not significantly different with respect to UGT1A1 TA-repeat genotype frequencies. Conclusions: Our study of a well-phenotyped group of patients with intermittent claudication and control individuals revealed a clear association between low bilirubin concentrations and peripheral arterial disease but no association between the UGT1A1 polymorphism and the disease.

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“…[1][2][3][4][5] The strength of the association was similar to that of smoking, elevated systolic blood pressure, and low levels of high-density lipoprotein (HDL) cholesterol. 6,7 In a retrospective case-control study of individuals with early familial CHD onset, higher serum bilirubin concentrations within the normal range were associated with a significant and marked reduction in CHD risk. 3 Individuals with Gilbert syndrome who have mildly elevated bilirubin levels were found to have an ischemic heart disease rate of 2% compared with 12.1% in the general population.…”

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confidence: 99%

Association Between the UGT1A1*28 Allele, Bilirubin Levels, and Coronary Heart Disease in the Framingham Heart Study

et al. 2006

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Background-Bilirubin is an antioxidant that suppresses lipid oxidation and retards atherosclerosis formation. An inverse association between serum bilirubin and coronary heart disease has been reported. Linkage studies have identified a major locus at the chromosome 2q telomere that affects bilirubin concentrations. A candidate gene in the linkage region encodes hepatic bilirubin uridine diphosphate-glucuronosyltransferase (UGT1A1). The insertion of a TA in the TATAA box of the gene, an allele designated UGT1A1*28, decreases gene transcription. Individuals homozygous for UGT1A1*28 (genotype 7/7) have increased serum bilirubin levels compared with carriers of the 6 allele. To date, no significant association between UGT1A1*28 and cardiovascular disease (CVD) events has been reported. We performed an association study in the Framingham Heart Study population to investigate whether UGT1A1*28 is associated with the risk of CVD events. Methods and Results-The study population included 1780 unrelated individuals from the Offspring cohort (49% males, mean age 36 years at entry) who had been followed up for 24 years. Individuals with genotype 7/7 had significantly higher bilirubin levels (meanϮSD 1.14Ϯ0.44 mg/dL) than those with genotypes 6/6 and 6/7 (meanϮSD 0.69Ϯ0.27 mg/dL, PϽ0.01). Using the Cox proportional hazards model, we found significant associations between the UGT1A1*28 allele and decreased risk of CVD. Individuals with genotype 7/7 (population frequency of 11%) had approximately one third the risk for CVD and coronary heart disease as carriers of the 6 allele, which resulted in a hazard ratio (95% confidence interval) of 0.36 (0.18 to 0.74) and 0.30 (0.12 to 0.74), respectively. Conclusions-Homozygote UGT1A1*28 allele carriers with higher serum bilirubin concentrations exhibit a strong association with lower risk of CVD.

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Comparison of various lipid, lipoprotein, and bilirubin combinations as risk factors for predicting coronary artery disease

Cited by 58 publications

References 20 publications

Polymorphisms of the uridine-diphosphoglucuronosyltransferase 1A1 gene and coronary artery disease

Polymorphisms of the uridine-diphosphoglucuronosyltransferase 1A1 gene and coronary artery disease

Association between the UGT1A1 TA-Repeat Polymorphism and Bilirubin Concentration in Patients with Intermittent Claudication: Results from the CAVASIC Study

Association Between the UGT1A1*28 Allele, Bilirubin Levels, and Coronary Heart Disease in the Framingham Heart Study

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