Body Fat Percentage Is a Major Determinant of Total Bilirubin Independently of UGT1A1*28 Polymorphism in Young Obese

被引:24
作者
Belo, Luis [1 ,2 ]
Nascimento, Henrique [1 ,2 ]
Kohlova, Michaela [3 ]
Bronze-da-Rocha, Elsa [1 ,2 ]
Fernandes, Joao [1 ,3 ]
Costa, Elisio [1 ,2 ]
Catarino, Cristina [1 ,2 ]
Aires, Luisa [4 ,5 ]
Mansilha, Helena Ferreira [6 ]
Rocha-Pereira, Petronila [7 ]
Quintanilha, Alexandre [2 ,8 ]
Rego, Carla [9 ]
Santos-Silva, Alice [1 ,2 ]
机构
[1] Univ Porto, Fac Farm, Dept Ciencias Biol, P-4100 Oporto, Portugal
[2] Univ Porto, IBMC, P-4100 Oporto, Portugal
[3] Univ Coimbra, Fac Med, Inst Biomed Imaging & Life Sci IBILI, Coimbra, Portugal
[4] Univ Porto, Ctr Invest Actividade Fis Saude & Lazer CIAFEL, Fac Desporto, P-4100 Oporto, Portugal
[5] Inst Univ Maia ISMAI, Maia, Portugal
[6] Ctr Hosp Porto, Dept Infancia & Adolescencia, Serv Pediat, Oporto, Portugal
[7] Univ Beira Interior, Ctr Invest Ciencias Saude, Covilha, Portugal
[8] Univ Porto, ICBAS, P-4100 Oporto, Portugal
[9] Univ Porto, Fac Med, Ctr Hlth Technol & Serv Res CINTESIS, Hosp CUF Porto,Ctr Crianca & Adolescente, P-4100 Oporto, Portugal
关键词
SERUM BILIRUBIN; INSULIN-RESISTANCE; METABOLIC SYNDROME; OXIDATIVE STRESS; ENDOTHELIAL FUNCTION; INVERSE RELATIONSHIP; RACIAL VARIABILITY; CLINICAL-PRACTICE; MASS INDEX; GENE;
D O I
10.1371/journal.pone.0098467
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Objectives: Bilirubin has potential antioxidant and anti-inflammatory properties. The UGT1A1*28 polymorphism (TA repeats in the promoter region) is a major determinant of bilirubin levels and recent evidence suggests that raised adiposity may also be a contributing factor. We aimed to study the interaction between UGT1A1 polymorphism, hematological and anthropometric variables with total bilirubin levels in young individuals. Methods: 350 obese (mean age of 11.6 years; 52% females) and 79 controls (mean age of 10.5 years; 59% females) were included. Total bilirubin and C-reactive protein (CRP) plasma levels, hemogram, anthropometric data and UGT1A1 polymorphism were determined. In a subgroup of 74 obese and 40 controls body composition was analyzed by dual-energy X-ray absorptiometry. Results: The UGT1A1 genotype frequencies were 49.9%, 42.7% and 7.5% for 6/6, 6/7 and 7/7 genotypes, respectively. Patients with 7/7 genotype presented the highest total bilirubin levels, followed by 6/7 and 6/6 genotypes. Compared to controls, obese patients presented higher erythrocyte count, hematocrit, hemoglobin and CRP levels, but no differences in bilirubin or in UGT1A1 genotype distribution. Body fat percentage was inversely correlated with bilirubin in obese patients but not in controls. This inverse association was observed either in 6/7 or 6/6 genotype obese patients. UGT1A1 polymorphism and body fat percentage were the main factors affecting bilirubin levels within obese patients (linear regression analysis). Conclusion: In obese children and adolescents, body fat composition and UGT1A1 polymorphism are independent determinants of total bilirubin levels. Obese individuals with 6/6 UGT1A1 genotype and higher body fat mass may benefit from a closer clinical follow-up.
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页数:9
相关论文
共 49 条
[1]
Heme oxygenase: A target gene for anti-diabetic and obesity [J].
Abraham, N. G. ;
Tsenovoy, P. L. ;
McClung, J. ;
Drummond, G. S. .
CURRENT PHARMACEUTICAL DESIGN, 2008, 14 (05) :412-421
[2]
The influence of age and body mass index on the metabolic syndrome and its components [J].
Alexander, C. M. ;
Landsman, P. B. ;
Grundy, Scott M. .
DIABETES OBESITY & METABOLISM, 2008, 10 (03) :246-250
[3]
Acute effect of weight loss on levels of total bilirubin in obese, cardiovascular high-risk patients: an analysis from the lead-in period of the Sibutramine Cardiovascular Outcome trial [J].
Andersson, Charlotte ;
Weeke, Peter ;
Fosbol, Emil Loldrup ;
Brendorp, Bente ;
Kober, Lars ;
Coutinho, Walmir ;
Sharma, Arya M. ;
Van Gaal, Luc ;
Finer, Nick ;
James, W. Philip T. ;
Caterson, Ian D. ;
Rode, Richard A. ;
Torp-Pedersen, Christian .
METABOLISM-CLINICAL AND EXPERIMENTAL, 2009, 58 (08) :1109-1115
[4]
Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter:: A balanced polymorphism for regulation of bilirubin metabolism? [J].
Beutler, E ;
Gelbart, T ;
Demina, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (14) :8170-8174
[5]
Oxidative stress and inflammation interactions in human obesity [J].
Bondia-Pons, Isabel ;
Ryan, Lisa ;
Alfredo Martinez, J. .
JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY, 2012, 68 (04) :701-711
[6]
THE GENETIC-BASIS OF THE REDUCED EXPRESSION OF BILIRUBIN UDP-GLUCURONOSYLTRANSFERASE-1 IN GILBERTS-SYNDROME [J].
BOSMA, PJ ;
CHOWDHURY, JR ;
BAKKER, C ;
GANTLA, S ;
DEBOER, A ;
OOSTRA, BA ;
LINDHOUT, D ;
TYTGAT, GNJ ;
JANSEN, PLM ;
ELFERINK, RPJO ;
CHOWDHURY, NR .
NEW ENGLAND JOURNAL OF MEDICINE, 1995, 333 (18) :1171-1175
[7]
Intramuscular heat shock protein 72 and heme oxygenase-1 mRNA are reduced in patients with type 2 diabetes - Evidence that insulin resistance is associated with a disturbed antioxidant defense mechanism [J].
Bruce, CR ;
Carey, AL ;
Hawley, JA ;
Febbraio, MA .
DIABETES, 2003, 52 (09) :2338-2345
[8]
Insulin Up-Regulates Heme Oxygenase-1 Expression in 3T3-L1 Adipocytes via PI3-Kinase- and PKC-Dependent Pathways and Heme Oxygenase-1-Associated MicroRNA Downregulation [J].
Chang, Chih-Ling ;
Au, Lo-Chun ;
Huang, Seng-Wong ;
Kwok, Ching Fai ;
Ho, Low-Tone ;
Juan, Chi-Chang .
ENDOCRINOLOGY, 2011, 152 (02) :384-393
[9]
Chauhan Alia, 2013, FP Essent, V410, P25
[10]
Inheritance of hyperbilirubinemia: Evidence for a major autosomal recessive gene [J].
Clementi, M. ;
Di Gianantonio, E. ;
Fabris, L. ;
Forabosco, P. ;
Strazzabosco, M. ;
Tenconi, R. ;
Okolicsanyi, L. .
DIGESTIVE AND LIVER DISEASE, 2007, 39 (04) :351-355