The influence of uridine diphosphate glucuronosyl transferase 1A promoter polymorphisms, βS-globin gene haplotype, co-inherited α-thalassemia trait and Hb F on steady-state serum bilirubin levels in sickle cell anemia

A. Adekile, Ferdane Kutlar, K. McKie, A. Addington, D. Elam, L. Holley, B. Clair, Abdullah Kutlar

Research output: Contribution to journalArticle

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Abstract

Purpose: Homozygosity for the (AT)7 allele of uridine diphosphate glucuronosyl transferase 1A (UGT1A1) gene polymorphism is associated with increased bilirubin levels in sickle cell anemia (SCA). In the present study, in addition to UGT1A1 promoter genotype, serum bilirubin level was related to other genetic modifiers-βS-globin gene haplotype, Hb F, co-inherited α-thal trait, age and gender. Methods: The patients were randomly selected from the sickle cell clinic, Medical College of Georgia. UGT1A1 promoter polymorphisms were determined using automated sequencing. Other investigations were with standard techniques. Results: There were 67 SCA patients (41 males and 26 females), aged 2-44 yr (mean of 20.6 ± 10.7). Ten (14.9%) patients were homozygous for the (AT)6 UGT1A1 allele, 35 (52.2%) were heterozygous for (AT)6 and (AT)7 alleles while 22 (32.8%) were homozygous for (AT)7. Serum bilirubin was significantly higher in the homozygous (AT)7 group (3.7 ± 1.5, 3.8 ± 2.3 and 5.6 ± 2.4 mg/dL, respectively). It was also significantly higher in males than females and in patients aged > 10 yr. There was a significant negative linear correlation (r = -0.304, P = 0.016) of serum bilirubin with Hb F. The β-globin haplotype and co-existing α-thal trait did not have any significant influence on serum bilirubin levels. Patients on hydroxyurea were older, had lower Hb F, but higher mean serum bilirubin. The latter also was signifcantly higher among those with UGT1A1 (AT)7 homozygosity. Conclusions: Apart from UGT1A1 (AT)7 homozygosity, Hb F, age and gender are the other factors that significantly influence serum bilirubin level in SCA.

Original languageEnglish (US)
Pages (from-to)150-155
Number of pages6
JournalEuropean Journal of Haematology
Volume75
Issue number2
DOIs
StatePublished - Aug 1 2005

Fingerprint

Uridine Diphosphate
Thalassemia
Globins
Sickle Cell Anemia
Transferases
Bilirubin
Haplotypes
Serum
Genes
Alleles
Hydroxyurea
Genotype

Keywords

  • Serum bilirubin
  • Sickle cell anemia
  • Uridine diphosphate glucuronosyl transferase gene polymorphisms

ASJC Scopus subject areas

  • Hematology

Cite this

The influence of uridine diphosphate glucuronosyl transferase 1A promoter polymorphisms, βS-globin gene haplotype, co-inherited α-thalassemia trait and Hb F on steady-state serum bilirubin levels in sickle cell anemia. / Adekile, A.; Kutlar, Ferdane; McKie, K.; Addington, A.; Elam, D.; Holley, L.; Clair, B.; Kutlar, Abdullah.

In: European Journal of Haematology, Vol. 75, No. 2, 01.08.2005, p. 150-155.

Research output: Contribution to journalArticle

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abstract = "Purpose: Homozygosity for the (AT)7 allele of uridine diphosphate glucuronosyl transferase 1A (UGT1A1) gene polymorphism is associated with increased bilirubin levels in sickle cell anemia (SCA). In the present study, in addition to UGT1A1 promoter genotype, serum bilirubin level was related to other genetic modifiers-βS-globin gene haplotype, Hb F, co-inherited α-thal trait, age and gender. Methods: The patients were randomly selected from the sickle cell clinic, Medical College of Georgia. UGT1A1 promoter polymorphisms were determined using automated sequencing. Other investigations were with standard techniques. Results: There were 67 SCA patients (41 males and 26 females), aged 2-44 yr (mean of 20.6 ± 10.7). Ten (14.9{\%}) patients were homozygous for the (AT)6 UGT1A1 allele, 35 (52.2{\%}) were heterozygous for (AT)6 and (AT)7 alleles while 22 (32.8{\%}) were homozygous for (AT)7. Serum bilirubin was significantly higher in the homozygous (AT)7 group (3.7 ± 1.5, 3.8 ± 2.3 and 5.6 ± 2.4 mg/dL, respectively). It was also significantly higher in males than females and in patients aged > 10 yr. There was a significant negative linear correlation (r = -0.304, P = 0.016) of serum bilirubin with Hb F. The β-globin haplotype and co-existing α-thal trait did not have any significant influence on serum bilirubin levels. Patients on hydroxyurea were older, had lower Hb F, but higher mean serum bilirubin. The latter also was signifcantly higher among those with UGT1A1 (AT)7 homozygosity. Conclusions: Apart from UGT1A1 (AT)7 homozygosity, Hb F, age and gender are the other factors that significantly influence serum bilirubin level in SCA.",
keywords = "Serum bilirubin, Sickle cell anemia, Uridine diphosphate glucuronosyl transferase gene polymorphisms",
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T1 - The influence of uridine diphosphate glucuronosyl transferase 1A promoter polymorphisms, βS-globin gene haplotype, co-inherited α-thalassemia trait and Hb F on steady-state serum bilirubin levels in sickle cell anemia

AU - Adekile, A.

AU - Kutlar, Ferdane

AU - McKie, K.

AU - Addington, A.

AU - Elam, D.

AU - Holley, L.

AU - Clair, B.

AU - Kutlar, Abdullah

PY - 2005/8/1

Y1 - 2005/8/1

N2 - Purpose: Homozygosity for the (AT)7 allele of uridine diphosphate glucuronosyl transferase 1A (UGT1A1) gene polymorphism is associated with increased bilirubin levels in sickle cell anemia (SCA). In the present study, in addition to UGT1A1 promoter genotype, serum bilirubin level was related to other genetic modifiers-βS-globin gene haplotype, Hb F, co-inherited α-thal trait, age and gender. Methods: The patients were randomly selected from the sickle cell clinic, Medical College of Georgia. UGT1A1 promoter polymorphisms were determined using automated sequencing. Other investigations were with standard techniques. Results: There were 67 SCA patients (41 males and 26 females), aged 2-44 yr (mean of 20.6 ± 10.7). Ten (14.9%) patients were homozygous for the (AT)6 UGT1A1 allele, 35 (52.2%) were heterozygous for (AT)6 and (AT)7 alleles while 22 (32.8%) were homozygous for (AT)7. Serum bilirubin was significantly higher in the homozygous (AT)7 group (3.7 ± 1.5, 3.8 ± 2.3 and 5.6 ± 2.4 mg/dL, respectively). It was also significantly higher in males than females and in patients aged > 10 yr. There was a significant negative linear correlation (r = -0.304, P = 0.016) of serum bilirubin with Hb F. The β-globin haplotype and co-existing α-thal trait did not have any significant influence on serum bilirubin levels. Patients on hydroxyurea were older, had lower Hb F, but higher mean serum bilirubin. The latter also was signifcantly higher among those with UGT1A1 (AT)7 homozygosity. Conclusions: Apart from UGT1A1 (AT)7 homozygosity, Hb F, age and gender are the other factors that significantly influence serum bilirubin level in SCA.

AB - Purpose: Homozygosity for the (AT)7 allele of uridine diphosphate glucuronosyl transferase 1A (UGT1A1) gene polymorphism is associated with increased bilirubin levels in sickle cell anemia (SCA). In the present study, in addition to UGT1A1 promoter genotype, serum bilirubin level was related to other genetic modifiers-βS-globin gene haplotype, Hb F, co-inherited α-thal trait, age and gender. Methods: The patients were randomly selected from the sickle cell clinic, Medical College of Georgia. UGT1A1 promoter polymorphisms were determined using automated sequencing. Other investigations were with standard techniques. Results: There were 67 SCA patients (41 males and 26 females), aged 2-44 yr (mean of 20.6 ± 10.7). Ten (14.9%) patients were homozygous for the (AT)6 UGT1A1 allele, 35 (52.2%) were heterozygous for (AT)6 and (AT)7 alleles while 22 (32.8%) were homozygous for (AT)7. Serum bilirubin was significantly higher in the homozygous (AT)7 group (3.7 ± 1.5, 3.8 ± 2.3 and 5.6 ± 2.4 mg/dL, respectively). It was also significantly higher in males than females and in patients aged > 10 yr. There was a significant negative linear correlation (r = -0.304, P = 0.016) of serum bilirubin with Hb F. The β-globin haplotype and co-existing α-thal trait did not have any significant influence on serum bilirubin levels. Patients on hydroxyurea were older, had lower Hb F, but higher mean serum bilirubin. The latter also was signifcantly higher among those with UGT1A1 (AT)7 homozygosity. Conclusions: Apart from UGT1A1 (AT)7 homozygosity, Hb F, age and gender are the other factors that significantly influence serum bilirubin level in SCA.

KW - Serum bilirubin

KW - Sickle cell anemia

KW - Uridine diphosphate glucuronosyl transferase gene polymorphisms

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