title: Lack of association of G779A ZHX-2 gene variant with HbF levels in β-thalassemia major.
abstract: The inherited disorders of hemoglobin synthesis are the most common monogenic disorders worldwide. They include thalassemias, hemoglobin variants, and hereditary persistence of fetal hemoglobin. β-thalassemia is the most common monogenic disorder in India. Clinical manifestations of β-thalassemia are extremely variable in severity. The reasons for this heterogeneity are not very well understood. Previous studies have shown that the genetic variants that modulate HbF levels have a very strong impact on ameliorating the clinical phenotype. In the present study, 5570 blood samples from suspected cases were analyzed using HPLC, amplification refractory mutation system-PCR and reverse dot blot techniques. Of 5570 individuals, we found 676 cases of β-thalassemia disease. Molecular analysis revealed the presence of different β-thalassemia mutations in the population under study. Patients with β-thalassemia were classified into mild, moderate, and severe according to severity score based on Hb level, age of onset, age at which patients received their first blood transfusion, degree of growth retardation and splenectomy. Patients with β-thalassemia were analyzed for zinc finger and homeoboxes 2 (ZHX2) G779A polymorphism, and the association between ZHX2 gene polymorphism and severity of β-thalassemia was evaluated. We did not find a significant difference in genotypic and allelic frequency of ZHX2 gene between mild and moderate, mild and severe, and moderate and severe cases. There was no significant difference in high and low percentage of HbF in GG, GA, and AA bearing individuals showing that ZHX2 gene variant has no role in ameliorating the severity of β-thalassemia major in the South Indian population from Andhra Pradesh.
authors: Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad, India. anjanadurani@yahoo.co.in
authors: Anjana
authors: A
authors: Munshi
authors: Sneha
authors: S
authors: Dadheech
authors: Suman
authors: S
authors: Jain
authors: James
authors: J
authors: Joseph
authors: Amal
authors: A
authors: Al-Hazzani
authors: Ali A
authors: AA
authors: Alshatwi
authors: Mallemoggala
authors: M
authors: Sai Babu
authors: Koppula
authors: K
authors: Rajeshwar
authors: Akka
authors: A
authors: Jyothy
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics / Q000378:metabolism*; D005787:Gene Frequency; D056726:Genetic Association Studies; D014644:Genetic Variation; D018398:Homeodomain Proteins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007194:India; D008297:Male; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult; D017086:beta-Thalassemia / Q000097:blood* / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors; C476826:ZHX2 protein, human; D005319:Fetal Hemoglobin