Evaluation of<i>UGT1A1</i>and<i>SULT1A1</i>polymorphisms with lipid levels in women with different hormonal status

Smiderle, Lisiane; Galvão, Ananda Cristine Santos; Fontana, Crisciele; Wender, Maria Celeste Osório; Agnes, Grasiela; Giovenardi, Márcia; Hutz, Mara H.; Almeida, Silvana

doi:10.3109/09513590.2010.493248

Cited by 7 publications

(5 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data fail to support data presented by Tapan et al [56] who showed reduced sd-LDL in a cohort of male, age and BMI matched individuals, indicating the possibility of gender dependent perturbation of cholesterol homeostasis in GS. Such conclusions are further supported by the elegant experiments of Smiderle et al [57], who showed premenopausal women possessing the 7/7 TA repeat polymorphism had significantly reduced TC concentrations, versus individuals with the 6/7 or 6/6 polymorphism. The 7/7 TA repeat polymorphism is associated with hyperbilirubinemia [58], however, bilirubin concentrations were not reported in this study.…”

Section: Bilirubin and Lipid Status 141 Gilbert's Syndromementioning

confidence: 71%

Bilirubin and beyond: A review of lipid status in Gilbert’s syndrome and its relevance to cardiovascular disease protection

Bulmer

Verkade

Wagner

2013

Progress in Lipid Research

113

120

View full text Add to dashboard Cite

Gilbert's syndrome (GS) is characterized by a benign, mildly elevated bilirubin concentration in the blood. Recent reports show clear protection from cardiovascular disease in this population. Protection of lipids, proteins and other macromolecules from oxidation by bilirubin represents the most commonly accepted mechanism contributing to protection in this group. However, a recent meta-analysis estimated that bilirubin only accounts for ~34% of the cardioprotective effects within analysed studies. To reveal the additional contributing variables we have explored circulating cholesterol and triacylglycerol concentrations, which appear to be decreased in hyperbilirubinemic individuals/animals, and are accompanied by lower body mass index in highly powered studies. These results suggest that bilirubin could be responsible for the development of a lean and hypolipidemic state in GS. Here we also discuss the possible contributing mechanisms that might reduce circulating cholesterol and triacylglycerol concentrations in individuals with syndromes affecting bilirubin metabolism/excretion, which we hope will stimulate future research in the area. In summary, this article is the first review of lipid status in animal and human studies of hyperbilirubinemia and explores possible mechanisms that could contribute to lowering circulating lipid parameters and further explain cardiovascular protection in Gilbert's syndrome.

show abstract

Section: Bilirubin and Lipid Status 141 Gilbert's Syndromementioning

confidence: 71%

Bilirubin and beyond: A review of lipid status in Gilbert’s syndrome and its relevance to cardiovascular disease protection

Bulmer

Verkade

Wagner

2013

Progress in Lipid Research

113

120

View full text Add to dashboard Cite

show abstract

“…39,40 In addition, a recent study confirmed that there was an association between the uridine 5'-diphospho-glucuronosyltransferase 1A1 and TC and LDL-C levels in women with different hormonal status. 41 Similarly, a negative correlation between TB and blood pressure was only found in women. 42 Further research is warranted to clarify the sex difference of the effects of bilirubin.…”

Section: Discussionmentioning

confidence: 99%

Decreased Serum Bilirubin Is Associated With Silent Cerebral Infarction

Cao

Zhang

et al. 2014

ATVB

View full text Add to dashboard Cite

946S ilent cerebral infarction (SCI) is a cerebral infarction that is evident on brain imaging but is not associated with a clinical symptom. In most cases, SCI is found as a lacunar infarction, that is, a small, deep cerebral infarct caused by occlusion of small penetrating cerebral arteries. Recent studies demonstrated that the presence of SCI predicts transient ischemia attack, clinically overt stroke, cardiovascular disease, and dementia. 1-3 See accompanying editorial on page 702A large body of evidence has highlighted a role for oxidative stress in atherosclerosis. Oxidative stress is induced by increased production of reactive oxygen species or decreased antioxidant capacity of endogenous antioxidant systems. Bilirubin is an effective antioxidant molecule that suppresses the oxidation of lipids and prevents the formation of plaque. 4 In several cross-sectional studies, bilirubin levels were found to be decreased in carotid intima-media thickness, cardiovascular disease, stroke, and peripheral arterial disease.5-8 A meta-analysis further confirmed that bilirubin levels were reduced in coronary artery disease. 9 To the best of our knowledge, the relationship between bilirubin levels and SCI has not yet been reported. We, therefore, conducted this study to assess the bilirubin levels in general population. Materials and MethodsMaterials and Methods are available in the online-only Supplement. ResultsClinical and laboratory data of participants with and without SCI are shown in Table 1. Of the 2865 participants enrolled, 1831 (63.91%) were men and 1034 (36.09%) were women. Median (interquartile range) of total bilirubin (TB) concentration was 10.5 (7.8-13.8; range, 2.1-33.4) μmol/L in the whole cohort of individuals. Three hundred forty-three participants (11.97%; 274 men and 69 women) presented SCI. The patients with SCI were older and had higher body mass index (BMI), systolic blood pressure, diastolic blood pressure (DBP), total cholesterol (TC), triglyceride, low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), and brachial-ankle pulse wave velocity (baPWV) levels and reduced TB, indirect bilirubin, direct bilirubin, estimated glomerular filtration rate (eGFR), and high-density lipoprotein cholesterol levels compared with the subjects without SCI. However, the levels of aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, and current use of statins and calcium channel blocker drugs in the 2 groups had no difference. Male sex, smoking, alcohol consumption, type 2 diabetes mellitus (DM), hypertension, and current use of angiotensin-converting enzyme inhibitor/angiotensin II receptor antagonist, aspirin, and hypoglycemic drugs had a higher prevalence in SCI group.The demographic and biochemical characteristics of the study population according to TB quartiles are shown in Table 2 FPG, triglyceride, LDL-C, FPG, aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, and baPWV decreased gradually as TB increased. Also, the percentage ...

show abstract

“…Genomic DNA was extracted from leukocytes by a standard salting out methodology. The fragment containing the chromosomal region of interest of the UGT1A1 gene was amplified by polymerase chain reaction (PCR), using the primers described by Smiderle et al 9 The size of the amplicons was determined by capillary electrophoresis on the ABI PRISM 310 Genetic Analyzer (Applied Biosystems, USA).…”

mentioning

confidence: 99%

Short Communication: UGT1A128* Variant Allele Is a Predictor of Severe Hyperbilirubinemia in HIV-Infected Patients on HAART in Southern Brazil

Turatti

Sprinz

Lazzaretti

et al. 2012

AIDS Research and Human Retroviruses

Self Cite

View full text Add to dashboard Cite

Highly active antiretroviral therapy (HAART) has increased the survival of HIV-infected patients. However, adverse effects play a major role in adherence to HAART. Some protease inhibitors (mainly atazanavir and indinavir) act as inhibitors of uridine diphosphate-glucuronosyltransferase (UGT1A1), the enzyme responsible for hepatic conjugation of bilirubin. Variations in the promoter region of the UGT1A1 gene (UGT1A1*28, rs8175347) can influence bilirubin plasma levels, modulating the susceptibility to hyperbilirubinemia. Aiming to analyze the association between UGT1A1*28 allele and hyperbilirubinemia in individuals exposed to HAART, we evaluated 375 HIV-positive individuals on antiretroviral therapy. Individuals carrying the UGT1A1*28 allele had a higher risk of developing severe hyperbilirubinemia [prevalence ratio (PR)=2.43, 95% confidence interval (CI) 1.08-5.45, p=0.032] as well as atazanavir users (PR=7.72, 95% CI=3.14-18.98, p<0.001). This is the first description of such an association in Brazilian HIV patients, which shows that in African-American and Euroamerican HAART users, the UGT1A1*28 allele also predisposes to severe hyperbilirubinemia, especially in those exposed to atazanavir.

show abstract

Evaluation ofUGT1A1andSULT1A1polymorphisms with lipid levels in women with different hormonal status

Cited by 7 publications

References 44 publications

Bilirubin and beyond: A review of lipid status in Gilbert’s syndrome and its relevance to cardiovascular disease protection

Bilirubin and beyond: A review of lipid status in Gilbert’s syndrome and its relevance to cardiovascular disease protection

Decreased Serum Bilirubin Is Associated With Silent Cerebral Infarction

Short Communication: UGT1A128* Variant Allele Is a Predictor of Severe Hyperbilirubinemia in HIV-Infected Patients on HAART in Southern Brazil

Contact Info

Product

Resources

About

Evaluation ofUGT1A1andSULT1A1polymorphisms with lipid levels in women with different hormonal status

Cited by 7 publications

References 44 publications

Bilirubin and beyond: A review of lipid status in Gilbert’s syndrome and its relevance to cardiovascular disease protection

Bilirubin and beyond: A review of lipid status in Gilbert’s syndrome and its relevance to cardiovascular disease protection

Decreased Serum Bilirubin Is Associated With Silent Cerebral Infarction

Short Communication: UGT1A1*28 Variant Allele Is a Predictor of Severe Hyperbilirubinemia in HIV-Infected Patients on HAART in Southern Brazil

Contact Info

Product

Resources

About

Short Communication: UGT1A128* Variant Allele Is a Predictor of Severe Hyperbilirubinemia in HIV-Infected Patients on HAART in Southern Brazil