Further Evidence That the UGT1A1*28 Allele Is Not Associated with Coronary Heart Disease: The ECTIM Study

Gajdos, Vincent; Petit, François; Perret, Claire; Mollet-Boudjemline, A.; Colin, Patrice; Capel, Liliane; Nicaud, Viviane; Evans, Alun; Arveiler, Dominique; Parisot, Frédéric; Francoual, J; Génin, Emmanuelle; Cambien, François; Labrune, Philippe

doi:10.1373/clinchem.2006.078667

Cited by 33 publications

(31 citation statements)

References 7 publications

(1 reference statement)

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“…The "survival bias" (31) might lead to the particular effect of the genotype in HD patients being different from the general population. These distinctive features may explain the discrepancy in the results between our study and others (23)(24)(25)(26).…”

Section: Discussioncontrasting

confidence: 99%

“…Although most previous studies found an association between bilirubin levels and atherosclerosis outcome, only the prospective Framingham Heart Study (22) found an association between the polymorphism and CV endpoints. The major difference between these studies is that the Framingham Study (22) was a prospective populationbased cohort study in which subjects were followed for 24 years, whereas the other studies (23)(24)(25)(26) were retrospective cross-sectional case-control studies.…”

Section: Discussionmentioning

confidence: 99%

“…It is noteworthy that ethnic differences do exist with regard to the UGT1A1*28 polymorphism (21). A few studies have investigated the association of the UGT1A1*28 allele with CV diseases (CVD) (22)(23)(24)(25)(26). Only the prospective Framingham Heart Study (22), which followed subjects for 24 years, found an association between the polymorphism and CV endpoints.…”

Section: Introductionmentioning

confidence: 99%

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Serum Bilirubin Links UGT1A1*28 Polymorphism and Predicts Long-Term Cardiovascular Events and Mortality in Chronic Hemodialysis Patients

Chen¹,

Hung

Tarng

2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Bilirubin is a protective factor with antioxidant and anti-inflammatory properties, but its association with clinical outcomes of hemodialysis patients is unknown. Bilirubin degradation is mainly determined by the activity of hepatic bilirubin uridine diphosphate-glucuronosyltransferase (UGT1A1), which is significantly influenced by a TA-repeat polymorphism in the gene's promoter, an allele designated UGT1A1*28. The study aimed to clarify the association between serum bilirubin and UGT1A1*28 polymorphism and their respective effect on outcomes of chronic hemodialysis patients. Design, setting, participants, & measurementsThe cohort study comprised 661 chronic hemodialysis patients who were prospectively followed for 12 years. The endpoints were cardiovascular events (CVEs) and allcause mortality.Results After adjustment for traditional and dialysis-related risk factors, individuals with bilirubin in the upper tertile had an adjusted hazard ratio of 0.32 for CVEs and 0.48 for all-cause mortality compared with those in the lower tertile. Individuals homozygous for UGT1A1*28 (genotype 7/7) had significantly higher bilirubin levels than those with 6/6 and 7/6 genotypes. In the same multivariable-adjusted model, individuals with 7/7 had approximately one tenth the risk for CVEs and one fourth the risk for all-cause mortality as compared with carriers of the 6 allele.Conclusions A graded, reverse association was noted between serum bilirubin and adverse outcomes among chronic hemodialysis patients. Moreover, the UGT1A1*28 polymorphism had strong effects on bilirubin levels and the 7/7 genotype might have an important effect on reducing CVEs and death.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Serum Bilirubin Links UGT1A1*28 Polymorphism and Predicts Long-Term Cardiovascular Events and Mortality in Chronic Hemodialysis Patients

Chen¹,

Hung

Tarng

2011

Clinical Journal of the American Society of Nephrology

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“…Vitek et al 21 pointed that patients with mild increase of serum bilirubin could be protected against heart disease. But on the other hand, Bosma et al 22 and Gajdos et al 23 in two different studies did not find any correlation between mutations in UGT1A1 gene promoter and protection against heart disease. Moreover an eventual protective effect would be observed after reproductive age.…”

Section: Discussionmentioning

confidence: 92%

The Tunisian population history through the Crigler–Najjar type I syndrome

et al. 2008

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Crigler-Najjar syndrome type I (CN-I) is a rare and severe metabolic disorder. A recurrent mutationc.1070A4G in exon 3 -was identified in the Tunisian population, suggesting a founder effect. In 2004, the detection of this mutation in two Kuwaiti Bedouin families has called the Tunisian founder effect in question again. To determine the origin of this mutation, 21 Tunisian and 2 Kuwaiti Bedouin CN-I patients were screened using nine genetic markers. Haplotype analysis confirmed the founder effect hypothesis and dated the appearance of this mutation some 32 generations ago in the Tunisian population. Using the same genetic analysis, the ancestor haplotype was identified in these two families. This result genetically confirms the blending of the Bedouin nomads within today's Tunisian population. After population migration from east to west, this mutation was introduced into the Tunisian population, and then perpetuated, probably because of marriages in isolated communities.

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“…Subsequently, a prospective study involving 1,780 individuals from the Framingham Heart Study Offspring cohort found that UGT1A1 polymorphism resulting in higher bilirubin levels was associated with lower risk of cardiovascular events [36]. Again, however, some other smaller studies have failed to show the same association between UGT1A1 polymorphism and CVD [18,34,47]. It is possible that these smaller studies lack the statistical power to detect this association.…”

Section: Discussionmentioning

confidence: 99%

Plasma total bilirubin levels predict amputation events in type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

et al. 2013

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Aims/hypothesis Bilirubin has antioxidant and antiinflammatory activities. Previous studies demonstrated that higher bilirubin levels were associated with reduced prevalence of peripheral arterial disease (PAD). However, the relationship between bilirubin and lower-limb amputation, a consequence of PAD, is currently unknown. We hypothesised that, in patients with type 2 diabetes, bilirubin concentrations may inversely associate with lower-limb amputation.Methods The relationship between baseline plasma total bilirubin levels and amputation events was analysed in 9,795 type 2 diabetic patients from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. The analysis plan was pre-specified. Lower-limb amputation was adjudicated blinded to treatment allocation. Relevant clinical and biochemical data were available for analyses. Amputation was a pre-specified tertiary endpoint. Results Bilirubin concentrations were significantly inversely associated with lower-limb amputation, with a greater than M. K. C. Ng and A. C. Keech are joint senior authors of this study Electronic supplementary material The online version of this article

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Further Evidence That the UGT1A1*28 Allele Is Not Associated with Coronary Heart Disease: The ECTIM Study

Cited by 33 publications

References 7 publications

Serum Bilirubin Links UGT1A1*28 Polymorphism and Predicts Long-Term Cardiovascular Events and Mortality in Chronic Hemodialysis Patients

Serum Bilirubin Links UGT1A1*28 Polymorphism and Predicts Long-Term Cardiovascular Events and Mortality in Chronic Hemodialysis Patients

The Tunisian population history through the Crigler–Najjar type I syndrome

Plasma total bilirubin levels predict amputation events in type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

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