title: Multicenter study of the molecular basis of thalassemia intermedia in different ethnic populations.
abstract: We studied 325 thalassemia intermedia patients from Iran, India, Pakistan, Thailand, Mauritius and Cyprus to examine factors which influence the phenotype. The beta-thalassemia (thal) mutations were determined for 219 beta-thal/beta-thal and 106 beta-thal/Hb E [beta26(B8)Glu-->Lys, GAG-->AAG] thalassemia intermedia patients. Thirty-one different mutations were identified, and their combination gave rise to more than 44 different genotypes, of which 14 (31.8%) had the beta(0)/beta(0), 21 (47.7%) the beta(0)/beta(+) and nine (20.5%) the beta(+)/beta(+) types. Thus, the beta(+)-thal mutations were present in 68.2% of patients. alpha-Thalassemia mutations were present in frequencies higher than in the general population of all ethnic groups studied, as 45% of the patients carried alpha-thal mutations. Correlation of alpha-thal mutations with beta-globin mutations showed that the alpha-thal mutations were mainly co-inherited with the beta(+)-thal mutations. The XmnI (G)gamma polymorphic site at -158 (C-->T) was positive (T) in nine (8.8%) of 102 patients of the beta(+)/beta(+) genotype, and the percentage of both XmnI (G)gamma polymorphism [+/-] (T/C) and [+/+] (T/T) genotypes increased to 42.9 and 87.3, respectively, in the beta(0)/beta(+) and beta(0)/beta(0) patients. This polymorphism was found in the majority of beta(+)-thal/Hb E compound heterozygote patients (88.6%), and beta(0)-thal/Hb E patients (84.8%), suggesting that it could be linked to the Hb E chromosome. Therefore, the XmnI (G)gamma polymorphism at -158 (C-->T) was associated with beta(0)-thal mutations as well as the Hb E chromosome. The present study demonstrates that in cases of thalassemia intermedia with beta(+) mutations, the common ameliorating factor is the presence of alpha-thal mutations, while in cases with beta(0) mutations, the common ameliorating factor is the presence of the XmnI (G)gamma polymorphism at -158 (C-->T).
authors.affiliation: Sir Ganga Ram Hospital, Rajender Nagar, New Delhi, India.
authors.forename: Ishwar C
authors.initials: IC
authors.lastname: Verma
authors.forename: Marina
authors.initials: M
authors.lastname: Kleanthous
authors.forename: Renu
authors.initials: R
authors.lastname: Saxena
authors.forename: Suthat
authors.initials: S
authors.lastname: Fucharoen
authors.forename: Pranee
authors.initials: P
authors.lastname: Winichagoon
authors.forename: Sheikh
authors.initials: S
authors.lastname: Raizuddin
authors.forename: Shaheen N
authors.initials: SN
authors.lastname: Khan
authors.forename: Mohammad T
authors.initials: MT
authors.lastname: Akbari
authors.forename: Mina
authors.initials: M
authors.lastname: Izadyar
authors.forename: Navratnam
authors.initials: N
authors.lastname: Kotea
authors.forename: John M
authors.initials: JM
authors.lastname: Old
authors.forename: Panayiotis A
authors.initials: PA
authors.lastname: Ioannou
authors.forename: Baldip
authors.initials: B
authors.lastname: Khan
mesh_terms: D005006:Ethnicity; D005838:Genotype; D006801:Humans; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D017085:alpha-Thalassemia / Q000208:ethnology* / Q000235:genetics*; D017086:beta-Thalassemia / Q000208:ethnology* / Q000235:genetics*