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Evaluation of Glutathione-S-Transferase P1 Polymorphism and its Relation to Bone Mineral Density in Egyptian Children and Adolescents with Beta-Thalassemia Major.

Ragab SM, Badr EA, Ibrahim AS - Mediterr J Hematol Infect Dis (2016)

Bottom Line: They exhibited higher osteocalcin levels compared to heterozygotes and wild homozygotes (p=0.012, p=0.013, respectively).Ile105Val polymorphism was frequent among TM patients and could increase their susceptibility to reduced BMD.Large sample studies are required to confirm these findings.

View Article: PubMed Central - PubMed

Affiliation: Departments of Pediatrics, Faculty of Medicine, Menoufia University, NaserStreet, Shebeen El-koom, Menoufia, Egypt.

ABSTRACT

Background: Osteoporosis is a major complication of beta thalassemia major (TM). Increased oxidative stress and its controlling genes were linked to osteoporosis. Ile105 Val variant is a functional polymorphism of Glutathione S-transferase P1 (GSTP1), with reduced anti-oxidative property. No data are available about this variant or its association with osteoporosis among thalassemia patients yet.

Objectives: To investigate Ile105Val polymorphism and its possible association with bone mineral density (BMD) values in a group of TM children.

Methods: Thirty five TM children and 30 age and sex matched healthy controls were included. Liver and renal functions, serum ferritin, calcium, phosphorous, alkaline phosphatase and osteocalcin were assayed. BMD was determined by DXA with calculation of Z-scores at lumbar spine (LS) and femoral neck (FN). Height for age Z- score (HAZ) adjusted BMD Z-scores were calculated. GSTP1 Ile105Val polymorphism was studied by polymerase chain reaction-restriction fragment length polymorphism.

Results: The relative frequency of 105 Val allele was significantly higher in TM patients than the controls (p<0.0001). Significant association between genotype subgroups and BMD parameters was detected. Compared to wild homozygotes, polymorphic homozygotes had lower LS-BMD (p =0.029), LS-BMD Z -score (p=0.008 ), LS- BMD haz - Z-score (p=0.011), FN- BMD (p= 0.001), FN- BMD Z -score (p=0.02) and FN-BMD haz - Z-score (p=0.001). They exhibited higher osteocalcin levels compared to heterozygotes and wild homozygotes (p=0.012, p=0.013, respectively).

Conclusion: Ile105Val polymorphism was frequent among TM patients and could increase their susceptibility to reduced BMD. Large sample studies are required to confirm these findings.

No MeSH data available.


Related in: MedlinePlus

A. Comparison between different GSTP1 genotypes in DXA scan parameters among the patient group. B. Comparison between different GSTP1 genotypes in the studied laboratory parameters among the patient group.
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f3-mjhid-8-1-e2016004: A. Comparison between different GSTP1 genotypes in DXA scan parameters among the patient group. B. Comparison between different GSTP1 genotypes in the studied laboratory parameters among the patient group.

Mentions: Among children with TM, no significant difference was found in the clinical parameters between Ile105Val polymorphism genotype subgroups. Patients with Ile105Val polymorphism (homozygotes and heterozygotes) had significant lower BMD- LS, BMD LS-Z- score, FN- BMD and FN - BMD haz Z-score (p<0.05) with modest significant lower BMD haz Z-score at LS (p=0.05) than those without this polymorphism. No significant difference was found in any of the tested biochemical parameters between patients with Ile105Val polymorphism and those who do not carry this polymorphism. Significant association was found between Ile105Val polymorphism genotype subgroups and BMD (p<0.05). Post hoc analysis revealed that heterozygotes had significant lower FN-BMD and FN-BMD haz Z-score (p=0.006 and 0.02, respectively) with modest lower LS- BMD (p=0.05) and LS- BMD Z-score (p=0.08) compared to the wild homozygotes. In comparison to wild homozygotes, Ile105Val polymorphism homozygotes had significant lower LS-BMD (p =0.029), LS-BMD Z –score (p=0.008 ), LS- BMD haz Z-score (p=0.011), FN- BMD (p= 0.001), FN- BMD Z –score (p=0.02) and FN- BMD haz Z-score (p=0.001). Polymorphism homozygotes also had a trend of lower LS- BMD haz Z-score than the heterozygotes (p=0.09). Osteocalcin level was significantly higher in the polymorphic homozygotes compared to heterozygotes and wild homozygotes (p=0.012 and p=0.013, respectively). No significant difference was observed regarding the other tested parameters (Table 2, Figure 3).


Evaluation of Glutathione-S-Transferase P1 Polymorphism and its Relation to Bone Mineral Density in Egyptian Children and Adolescents with Beta-Thalassemia Major.

Ragab SM, Badr EA, Ibrahim AS - Mediterr J Hematol Infect Dis (2016)

A. Comparison between different GSTP1 genotypes in DXA scan parameters among the patient group. B. Comparison between different GSTP1 genotypes in the studied laboratory parameters among the patient group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4696466&req=5

f3-mjhid-8-1-e2016004: A. Comparison between different GSTP1 genotypes in DXA scan parameters among the patient group. B. Comparison between different GSTP1 genotypes in the studied laboratory parameters among the patient group.
Mentions: Among children with TM, no significant difference was found in the clinical parameters between Ile105Val polymorphism genotype subgroups. Patients with Ile105Val polymorphism (homozygotes and heterozygotes) had significant lower BMD- LS, BMD LS-Z- score, FN- BMD and FN - BMD haz Z-score (p<0.05) with modest significant lower BMD haz Z-score at LS (p=0.05) than those without this polymorphism. No significant difference was found in any of the tested biochemical parameters between patients with Ile105Val polymorphism and those who do not carry this polymorphism. Significant association was found between Ile105Val polymorphism genotype subgroups and BMD (p<0.05). Post hoc analysis revealed that heterozygotes had significant lower FN-BMD and FN-BMD haz Z-score (p=0.006 and 0.02, respectively) with modest lower LS- BMD (p=0.05) and LS- BMD Z-score (p=0.08) compared to the wild homozygotes. In comparison to wild homozygotes, Ile105Val polymorphism homozygotes had significant lower LS-BMD (p =0.029), LS-BMD Z –score (p=0.008 ), LS- BMD haz Z-score (p=0.011), FN- BMD (p= 0.001), FN- BMD Z –score (p=0.02) and FN- BMD haz Z-score (p=0.001). Polymorphism homozygotes also had a trend of lower LS- BMD haz Z-score than the heterozygotes (p=0.09). Osteocalcin level was significantly higher in the polymorphic homozygotes compared to heterozygotes and wild homozygotes (p=0.012 and p=0.013, respectively). No significant difference was observed regarding the other tested parameters (Table 2, Figure 3).

Bottom Line: They exhibited higher osteocalcin levels compared to heterozygotes and wild homozygotes (p=0.012, p=0.013, respectively).Ile105Val polymorphism was frequent among TM patients and could increase their susceptibility to reduced BMD.Large sample studies are required to confirm these findings.

View Article: PubMed Central - PubMed

Affiliation: Departments of Pediatrics, Faculty of Medicine, Menoufia University, NaserStreet, Shebeen El-koom, Menoufia, Egypt.

ABSTRACT

Background: Osteoporosis is a major complication of beta thalassemia major (TM). Increased oxidative stress and its controlling genes were linked to osteoporosis. Ile105 Val variant is a functional polymorphism of Glutathione S-transferase P1 (GSTP1), with reduced anti-oxidative property. No data are available about this variant or its association with osteoporosis among thalassemia patients yet.

Objectives: To investigate Ile105Val polymorphism and its possible association with bone mineral density (BMD) values in a group of TM children.

Methods: Thirty five TM children and 30 age and sex matched healthy controls were included. Liver and renal functions, serum ferritin, calcium, phosphorous, alkaline phosphatase and osteocalcin were assayed. BMD was determined by DXA with calculation of Z-scores at lumbar spine (LS) and femoral neck (FN). Height for age Z- score (HAZ) adjusted BMD Z-scores were calculated. GSTP1 Ile105Val polymorphism was studied by polymerase chain reaction-restriction fragment length polymorphism.

Results: The relative frequency of 105 Val allele was significantly higher in TM patients than the controls (p<0.0001). Significant association between genotype subgroups and BMD parameters was detected. Compared to wild homozygotes, polymorphic homozygotes had lower LS-BMD (p =0.029), LS-BMD Z -score (p=0.008 ), LS- BMD haz - Z-score (p=0.011), FN- BMD (p= 0.001), FN- BMD Z -score (p=0.02) and FN-BMD haz - Z-score (p=0.001). They exhibited higher osteocalcin levels compared to heterozygotes and wild homozygotes (p=0.012, p=0.013, respectively).

Conclusion: Ile105Val polymorphism was frequent among TM patients and could increase their susceptibility to reduced BMD. Large sample studies are required to confirm these findings.

No MeSH data available.


Related in: MedlinePlus