UDP‐glucuronosyltransferase 1 gene promoter polymorphism is associated with increased serum bilirubin levels and cholecystectomy in patients with sickle cell anemia

Fertrin, Kleber Yotsumoto; Melo, Mônica Barbosa de; Assis, Ângela Maria de; Saad, Sara Teresinha Olalla; Costa, Fernando Ferreira

doi:10.1034/j.1399-0004.2003.00113.x

Cited by 43 publications

(27 citation statements)

References 14 publications

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“…in b-thalassaemia (Galanello et al 1997(Galanello et al , 1999b, G6PD deficiency (Galanello et al 1999a) and SCD (Adekile et al 2005;Chaar et al 2005;Fertrin et al 2003;Harverfield et al 2005;Passon et al 2001). In fact, in addition to the results presented here, the mentioned studies performed in SCD (Table 1).…”

Section: Discussionmentioning

confidence: 75%

“…Although gallstones were identified at a mean age of 15.1 years in 40.6% of this cohort group, there was no association with UGT1A1 (TA) n genotypes (Harverfield et al 2005). On the other hand, Fertrin et al (2003) analysed a group of adult SCD patients (28.5 ± 10.7 years) and observed that although the frequency of cholelithiasis was higher in patients with the 7/7 genotype, the difference was not statistically significant (Fertrin et al 2003). Considering the need for cholecystectomy, the difference between 6/7 and 6/6 patients was statistically significant, although the difference between the other groups was not (Fertrin et al 2003).…”

Section: Discussionmentioning

confidence: 91%

“…On the other hand, Fertrin et al (2003) analysed a group of adult SCD patients (28.5 ± 10.7 years) and observed that although the frequency of cholelithiasis was higher in patients with the 7/7 genotype, the difference was not statistically significant (Fertrin et al 2003). Considering the need for cholecystectomy, the difference between 6/7 and 6/6 patients was statistically significant, although the difference between the other groups was not (Fertrin et al 2003). Furthermore, in studies performed in SCD children (3-19 years) the development of symptomatic cholelithiasis requiring cholecystectomy was significantly higher for children with the 7/7 genotype than those with the 6/7 or 6/6 genotypes (Passon et al 2001).…”

Section: Discussionmentioning

confidence: 99%

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Early modification of sickle cell disease clinical course by UDP-glucuronosyltransferase 1A1 gene promoter polymorphism

et al. 2008

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Elevated erythrocyte destruction in sickle cell disease (SCD) results in chronic hyperbilirubinaemia and, in a subset of patients, cholelithiasis occurs. We investigated whether the (TA) n promoter polymorphism in the UDP-glucuronosyltransferase 1A1 gene (UGT1A1) may modify bilirubin metabolism, influencing bilirubinaemia, predisposition to cholelithiasis and subsequent cholecystectomy, in a group of 153 young SCD patients (mean age 12.0 ± 9.0 years) predominantly of Bantu beta S haplotype. The concomitant effect of alpha thalassaemia was also analysed. Among the several UGT1A1 genotypes found, the most frequent were the (TA) 6 /(TA) 6 (n = 37), (TA) 6 /(TA) 7 (n = 60) and (TA) 7 /(TA) 7 (n = 29). These groups of patients did not significantly differ in age, gender ratio and haemoglobin, foetal haemoglobin and reticulocyte levels. On the other hand, total bilirubin levels were significantly different between groups, with an increased (TA) repeat number being associated with higher bilirubinaemia. Furthermore, both cholelithiasis and cholecystectomy were more frequent in groups with higher (TA) repeat number, although the former association was not statistically significant. None of the mentioned parameters is statistically different within UGT1A1 groups with the presence of alpha thalassaemia. Thus, the UGT1A1 promoter polymorphism may represent an important nonglobin genetic modifier of Bantu SCD patients' clinical manifestations, even at a young age.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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Early modification of sickle cell disease clinical course by UDP-glucuronosyltransferase 1A1 gene promoter polymorphism

et al. 2008

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“…We and others have reported that the promoter polymorphism of UDP-glucuronosyltransferase 1A1 (UGT1A1) gene, encoding a key enzyme involved in hepatic bilirubin conjugation, is a major genetic risk factor for cholelithiasis in SCA patients [2][3][4]. The promoter region of UGT1A1 gene contains a run of variable number of thymine-adenine repeats, (TA) n (n ¼ 5 to 8) with an inverse relationship between the size of this microsatellite and the promoter activity.…”

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confidence: 99%

UGT1A1 polymorphism outweighs the modest effect of deletional (−3.7 kb) α‐thalassemia on cholelithogenesis in sickle cell anemia

et al. 2006

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Enhanced erythrocyte destruction in sickle cell anemia results in chronic hyperbilirubinemia. Only a subset of patients develop cholelithiasis. UGT1A1 promoter polymorphism is associated both with unconjugated bilirubin level and elevated risk for cholelithiasis in such subset. Here, we investigated the role of a-thalassemia, yet another genetic factor that modulates hemolysis, in conferring protection from cholelithiasis. We show that, although a-thalassemia is associated with modest reduction in hemolysis and unconjugated bilirubin level, UGT1A1 polymorphism outweighs its effect on cholethiogenesis in sickle cell anemia patients. Am. J. Hematol. 81:377-379, 2006. V V C 2006 Wiley-Liss, Inc.

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“…The presence of 7 TA repeats (UGT1A1*28) is associated with reduced UGT1A1 expression compared to the wildtype allele (UGT1A1*1), which contains 6 TA repeats. Homozygous individuals who carry the A (TA) 7 TAA allele show significantly higher plasma levels of unconjugated bilirubin caused by a 30% reduction in the transcription of UGT1A1 (Fertrin et al, 2003). Interethnic differences have been observed in the frequency of the UGT1A1*28 allele, which has an approximate incidence of 6-12% in the Caucasian population, 0-3% in the Asian population, and 16-19% in the African population (Zhou et al, 2008).…”

Section: Introductionmentioning

confidence: 95%

Polymorphism of UGT1A1*28 (TA)7 and liver damage in hepatitis B virus-positive patients in Albania

Marku

Maltese²,

Koni

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Hepatitis B virus (HBV) is the infectious agent of both acute and chronic hepatitis. HBV exists in multiple genotypic variants that differ in their capacity to become persistent chronic infections and in their clinical manifestations, including hepatocellular carcinoma. The 8 genotypes (A-H) of HBV show a specific worldwide geographic distribution and are correlated with different disease course, severity, and response to therapy. We isolated DNA from 75 HBV-positive blood donors, chosen randomly from the database of the National Blood Bank in Tirana, to specifically analyze the UGT1A1 polymorphism to determine its correlations with bilirubin levels and liver function. The large number of subjects who were HBV-positive carriers of 5222 E. Marku et al. ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (2): 5221-5228 (2015) heterozygosis or homozygosis for the UGT1A1*28 (TA) 7 polymorphism suggests that these individuals may be more susceptible to cancer and should follow a strict regime of prevention.

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UDP‐glucuronosyltransferase 1 gene promoter polymorphism is associated with increased serum bilirubin levels and cholecystectomy in patients with sickle cell anemia

Cited by 43 publications

References 14 publications

Early modification of sickle cell disease clinical course by UDP-glucuronosyltransferase 1A1 gene promoter polymorphism

Early modification of sickle cell disease clinical course by UDP-glucuronosyltransferase 1A1 gene promoter polymorphism

UGT1A1 polymorphism outweighs the modest effect of deletional (−3.7 kb) α‐thalassemia on cholelithogenesis in sickle cell anemia

Polymorphism of UGT1A1*28 (TA)7 and liver damage in hepatitis B virus-positive patients in Albania

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