Beta-thalassemia, one of the most common single-gene disorders, is the result of 
reduced or absent production of β-globin chains. Patients with β-thalassemia 
show weak genotype-phenotype correlations. Mitochondrial DNA polymorphisms are a 
potential source for different physiological and pathological characteristics 
and have been found to be associated as genetic modifiers with various 
pathophysiologies, including cancers and neurodegenerative diseases. A group of 
35 patients with β-thalassemia was investigated for the presence of mtDNA D-loop 
polymorphisms in comparison with 504 normal controls. We found four mtDNA D-loop 
polymorphisms at nucleotides 16,069C > T, 16,189T > C, 16,319G > A, and 
16,519T > C that showed significant differences between patients and normal 
subjects. There is no strong proof for the association of these polymorphisms 
with β-thalassemia. It is hypothesized that iron overload or its effects on 
sequestration of calcium or zinc can lead to oxidative stress and ROS production 
inside the mitochondria. Therefore, possible accompanying of mtDNA polymorphisms 
with β-thalassemia disease may complicate the genotype-phenotype correlation and 
could affect the clinical outcomes in the patients.