title: Frequency of Gγ-globin promoter -158 (C>T) XmnI polymorphism in patients with homozygous/compound heterozygous beta thalassaemia.
abstract: BACKGROUND
  Response to hydroxyurea therapy in homozygous or compound heterozygous beta thalassaemia (BT) has been reported as more favourable in the presence of XmnI polymorphism. The prevalence of XmnI polymorphism may vary with BT phenotypes and genotypes, and differs geographically in distribution. Prevalence of XmnI polymorphism is not known in northern Pakistan.
  
  
  OBJECTIVE
  To determine the frequency of Gγ-globin promoter -158 (C>T) XmnI polymorphism (XmnI polymorphism) in patients with homozygous or compound heterozygous beta thalassaemia.
  
  
  METHODS
  Polymerase chain reaction (PCR) for common beta thalassaemia mutations and Gγ-globin promoter -158 (C>T) XmnI polymorphism was performed on 107 blood samples of transfusion dependent beta thalassaemia (BT) patients in Pakistan. One hundred samples of unrelated BT traits and 94 samples of healthy subjects as controls were also analysed for BT mutations and XmnI polymorphism.
  
  
  RESULTS
  Out of 301 DNA samples, XmnI polymorphism was detected in 71(24%); in normal controls, XmnI polymorphism was detected in 34/94 (36%) subjects; while in homozygous/compound heterozygous BT, it was detected in 14/107(13%) patients (Fisher's exact test, p=.0002). In heterozygous BT group, XmnI polymorphism was detected in 23/100 subjects (Fisher's exact test, p=.03 with normal controls, and p=.049 with homozygous/compound heterozygous BT). The most common BT genotype was Frame Shift (Fr) 8-9/Fr 8-9, and none of the patients with this genotype had XmnI polymorphism. The second most common genotype was IVSI-5/IVSI-5; 4/26 (15%). Cases with this genotype had XmnI polymorphism.
  
  
  CONCLUSIONS
  XmnI polymorphism in homozygous/compound heterozygous BT group is 13%. The most common genotype associated with XmnI polymorphism was IVSI-5/IVSI-5.
authors.affiliation: Dept of Hematology, Institute of Pathology Rawalpindi, Pakistan. Electronic address: dr.nadir.ali@gmail.com.
authors.forename: Nadir
authors.initials: N
authors.lastname: Ali
authors.affiliation: Institute of Pathology, Rawalpindi, Pakistan. Electronic address: drayyub57@yahoo.com.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ayyub
authors.affiliation: Dept of Hematology, Institute of Pathology Rawalpindi, Pakistan. Electronic address: Saleem003@hotmail.com.
authors.forename: Saleem Ahmed
authors.initials: SA
authors.lastname: Khan
authors.affiliation: Islamic International Medical College and Genetic Resource Center, Rawalpindi, Pakistan. Electronic address: suhaib955@hotmail.com.
authors.forename: Suhaib
authors.initials: S
authors.lastname: Ahmed
authors.affiliation: Dept of Hematology, Institute of Pathology Rawalpindi, Pakistan. Electronic address: kakazmi@gmail.com.
authors.forename: Kazim
authors.initials: K
authors.lastname: Abbas
authors.affiliation: Dept of Hematology, Institute of Pathology Rawalpindi, Pakistan. Electronic address: hamidsaeed_malik@yahoo.com.
authors.forename: Hamid Saeed
authors.initials: HS
authors.lastname: Malik
authors.affiliation: Dept of Hematology, Institute of Pathology Rawalpindi, Pakistan. Electronic address: sunila.tashfeen@yahoo.com.
authors.forename: Sunila
authors.initials: S
authors.lastname: Tashfeen
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D010154:Pakistan; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D055815:Young Adult; D017086:beta-Thalassemia / Q000235:genetics*; D055545:gamma-Globins / Q000235:genetics*
chemical_list: D055545:gamma-Globins
keywords: Beta thalassemia; Hbf; Hydroxyurea; Xmn 1Gγ polymorphism