Preliminary Report on the Frequency of Pro12Ala Polymorphism of the Peroxisome Proliferator-Activated Receptor-gamma Gene in Egyptian β-Thalassemia Major Patients

Abstract

Osteoporosis represents an important cause of morbidity in adult thalassemic patients. Peroxisome proliferator-activated receptor-γ (PPAR γ) is a master transcriptional regulator involved in expression of probably hundreds of genes. Recent studies have suggested that PPAR-γ plays an important role in osteogenesis. Furthermore, PPARγ inhibition in mice, increased bone formation with no effect on bone resorption. Our aim was to investigate the frequency of Pro12Ala polymorphism (substitution of proline to alanine at codon 12 in exon B) of PPARγ gene in Egyptian β-thalassemia major (β-TM) patients and its influence on their bone mineral density (BMD). Blood samples from 30 β-TM patients and 10 healthy controls matched for age, sex and body weight were analyzed for PPARγ gene polymorphism using polymerase chain reaction-restriction fragment length polymorphism. BMD were measured in all patients and controls by a dual energy X-ray absorptiometry at the lumbar spine. Low BMD (Z score is -1 or lower) was present in all thalassemic cases. There was no statistically significant difference between BMD in thalassemic males (-3.43±-1.08) and females (-2.78±-0.81) (p=0.265). Pro12Ala polymorphism was present in 2 out of 30 (6.67%) β-TM patients with osteoporosis. One patient had heterozygous 12Ala polymorphism and the other had homozygous 12Ala polymorphism. Both had normal body mass index, lipid profile, ejection fraction and elevated serum ferritin. Only one male control (10%) has homozygous 12Ala polymorphism. This study suggests that Pro12Ala polymorphism is unrelated to BMD level in Egyptian thalassemic patients. Further studies on a larger population of patients are still needed to confirm this finding.