gilbert syndrome acts as a risk factor of developing gallstone among β hemoglobinopathy tunisian patients.

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Published Aug 21, 2015
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Vol. 93 No. 4 (2015): Issue Apr 2015

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Chaouch Leila
Kalai Miniar
Chaouachi Dorra
Mallouli Fethi
Hafsia Raouf
Ben Ammar Slim
Abbes Salem

Abstract

Background: As a result of chronic hemolysis, hyperbilirubinemia is often observed, leading to the formation of pigment cholelithiasis which could be busted by the presence of uridine diphosphoglucuronosyltransferase 1A1 defects.
Aim: Herein, we investigated the effect of glibert mutation on the occurrence of pigment cholelithiasis in Tunisian patients with beta (β) hemoglobinopathy including sickle cell anemia and β thalassemia (minor). Subjects and methods: Our study included 151 subjects divided in 75 SCA patients and 76 β thalassemia patients. Both groups of patients were divided into two sub-groups according to the presence or absence of cholelithiasis. The relationship between A(TA)nTAA variation of UGT1A1 gene, the serum bilirubin level and the occurrence of cholilithiasis was investigated.
Results: Our results show a significant association between genotypes carrying variant (TA)7 and hyperbilirubinemia (p<0.05). Furthermore, we demonstrated a significant association between (TA)6/(TA)7 and (TA)7/(TA)7 genotypes with cholelithiasis among sickle cell anemia and thalassemia patients (p<0.05).
Conclusion: Altogether, our data provide evidence that genotypes (TA)6/(TA)7 and (TA)7/(TA)7 and (TA)7 variant present a risk factor of developing gallstone among β hemoglobinopathy Tunisian patients.

Keywords:

Sickle cell anemia, βthalassemia, cholelithiasis, Gilbert Syndrome, Bilirubin glucuronidation, genetic variation, UGT1A1.

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References

  1. Angastiniotis M And Madel B. Global Epidemiology Of Hemoglobin Disorders. Blood 1998; 7: 1854-60.
  2. Beutler E, Gelbart T, Demina A. Racial Variability In The Udpglucuronosyltransferase 1 (Ugt1a1) Promoter: A Balanced Polymorphism For Regulation Of Bilirubin Metabolism. Proc Natl Acad Sci U S A 1998, 95:8170-4
  3. Meech R, Mackenzie. Structure And Function Of Uridine Diphosphate Glucuronosyltransferases. Clin Exp Pharmacol Physiol 1997; 24:907-15.
  4. Tukey Rh, Strassburg Cp. Human Udp-Glucuronosyltransferase: Metabolism, Expression, And Disease. Annu Rev Pharmacol Toxicol 2000; 40:581-616.
  5. Bosma Pj, Chowdury Jr, Bakker C, Et Al. The Genetic Basis Of The Reduced Expression Of Bilirubin Udp-Glucuronosyltransferase 1 In Gilbert's Syndrome. N Engl J Med 1995; 333:1171-1175.
  6. Kadakol A, Ghosh Ss, Sappal Bs, Et Al. Genetic Lesions Of BilirubinDiphosphoglucuronate Glucosyltransferase (Ugt1a1) Causing CriglerNajjar Gilbert Syndromes: Correlation Of Genotype To Phenotype. Hum Mutat 2000; 4:297-306.
  7. Tsezou A, Thetis M, Giannatou E, Et Al. Gilbert Syndrome As A Predisposing Factor For Cholelithiasis Risk In The Greek Adult Population. Gen. Test 2009; 13:143-6.
  8. Buch S, Schafmayer C, Volzke H, Et Al. Loci From A Genome-Wide Analysis Of Bilirubin Levels Are Associated With Gallstone Risk And Composition. Gastroenterology 2010; 139:1942-1951
  9. Krawczyk M, Wang Dq, Portincasa P, Et Al. Dissecting The Genetic Heterogeneity Of Gallbladder Stone Formation. Seminars In Liver Disease 2011; 31:157-72.
  10. Chaouch L, Said Y, Moumni I, Et Al. Implication Of Genetic Variation At The Promoter And Exon1 Of Ugt1a1 In Occurrence Of Cholelithiasis In Tunisia. Ann Biol Clin 2002; 6:702-6.
  11. Chaouch L, Talbi, Moumni I, Et Al. Early Complication In Sickle Cell Anemia Children Due To A(Ta)Ntaa Polymorphism At The Promoter Of Ugt1a1 Gene. Disease Markers 2013; 35: 1-6.
  12. Romana M, Kecklard L, Froger A, Et Al. Diverse Genetic Mechanisms Operate To Generate Atypical Bs Haplotypes In The Population Of Guadeloupe. Hemoglobin 2000; 24:77-87.
  13. Chouk I, Daoud Bb, Mellouli F, Et Al. Contribution To The Description Of The Beta-Thalassemia Spectrum In Tunisia And The Origin Of Mutation Diversity. Hemoglobin 2004; 28:189-95.
  14. Driss A, Asare Ko, Hibbert Jm , Et Al. Sickle Cell Disease In The Post Genomic Era: A Monogenic Disease With A Polygenic Phenotype. Genomics Insight 2009; 2:23-48.
  15. Fertrin Ky, Melo Mb, Assis Am, Et Al. Udpglucuronosyltransferase 1 Gene Promoter Polymorphism Is Associated With Increased Serum Bilirubin Levels And Cholecystectomy In Patients With Sickle Cell Anemia. Clin Genet 2003; 64: 160-2.
  16. Haverfied Ev, Mackenzie Ca, Forrester T, Et Al. Ugt1a1 Variation And Gallstone Formation In Sickle Cell Disease. Blood 2005; 105: 68-72.
  17. Chaar V, Kecklard L, Diara Jp, Et Al. Association Of Ugt1a1 Polymorphism With Prevalence And Age At Onset Of Cholelithiasis In Sickle Cell Anemia. Haematologica 2005; 2: 188-99.
  18. Premawardhena A, Fisher Ca, Fathiu F, Et Al. Genetic Derterminants Of Jaundice In Hemoglobin Eb Thalassemia. Lancet 2001; 357: 1945-6
  19. Galanello R, Piras S, Barella S, Et Al. Cholelithiasis And Gilbert's Syndrome In Homozygous Beta-Thalassemia. Br J Haematol 2001; 115: 926-8.
  20. Kalotychou V, Antonatou K, Tzanetea R, Et Al. Analysis Of The A(Ta)(N)Taa Configuration In The Promoter Region Of The Ugt1 A1 Gene In Greek Patients With Thalassemia Intermedia And Sickle Cell Disease. Blood Cells Mol Dis 2003; 1: 38-42.
  21. Borgna-Pignatti C, Rigon F, Merlo L , Et Al. Thalassemia Minor, The Gilbert Mutation, And The Risk Of Gallstones. Haematologica 2003; 10:1106-9.
  22. Galanello R, Cipollina Md, Dessi C, Et Al. Co-Inherited Gilbert's Syndrome: A Factor Determining Hyperbilirubinemia In Homozygous Beta-Thalassemia. Haematologica 1999; 84:103-5.
  23. Galanello R, Perseu L, Satta S, Et Al. Phenotype-Genotype Correlation In Î’-Thalassemia. Thalassemia Reports 2011; 1: E6.