Dataset Information

Is the rs1801282 (G/C) Polymorphism of PPAR - Gamma Gene Associated with T2DM in Iraqi People?

ABSTRACT: BACKGROUND:Pro12Ala (rs1801282) is a common polymorphism of the human PPAR-? gene. Studies have demonstrated conflicting results about its association with T2DM worldwide. There are no reports about such possible association among Iraqi people. OBJECTIVES:This study aims at finding out whether having the mutant allele (Ala12) might be associated with T2DM among Iraqi people. METHODS:One hundred and ninety-two Arabic Iraqi adult subjects (97 with T2DM and 95 controls) were genotyped using PCR- RFLP. Clinical, anthropometrical and biochemical variables were compared regarding the Pro12Ala genotypes. RESULTS:About 5.67% of people with diabetes were carriers of the (Ala12) allele versus 9.47% of controls. Allelic and genotypic frequencies were not statistically different among diabetics and controls [(?2= 1.99, p= 0.16) and (?2= 2.17, p= 0.14)]. Age, BMI and smoking- but not Pro12Ala - were independent risk factors for T2DM in our subjects. Pro12Ala was not associated with T2DM (Odd's ratio 0.55, 95% CI 0.23- 1.32, p= 0.14). CONCLUSIONS:Our study revealed a relatively high frequency of the Ala12 allele among Arabic Iraqis. These frequencies did not significantly differ between diabetics and controls indicating the absence of association of Pro12Ala with T2DM among Iraqis.

SUBMITTER: Al-Naemi AH

PROVIDER: S-EPMC5874364 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Is the rs1801282 (G/C) Polymorphism of <i>PPAR - Gamma</i> Gene Associated with T2DM in Iraqi People?

Al-Naemi Amjad Hazim AH Ahmad Akram Jarjees AJ

Open access Macedonian journal of medical sciences 20180314 3

<h4>Background</h4>Pro12Ala (rs1801282) is a common polymorphism of the human PPAR-γ gene. Studies have demonstrated conflicting results about its association with T2DM worldwide. There are no reports about such possible association among Iraqi people.<h4>Objectives</h4>This study aims at finding out whether having the mutant allele (Ala12) might be associated with T2DM among Iraqi people.<h4>Methods</h4>One hundred and ninety-two Arabic Iraqi adult subjects (97 with T2DM and 95 controls) were g ...[more]

PMID: 29610599

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Project description:Peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PPARGC1A) regulates the expression of energy metabolism's genes and mitochondrial biogenesis. The essential roles of PPARGC1A encouraged the researchers to assess the relation between metabolism-related diseases and its variants. To study Gly482Ser (+1564G/A) single-nucleotide polymorphism (SNP) after PPARGC1A modeling, we substitute Gly482 for Ser482. Stability prediction tools showed that this substitution decreases the stability of PPARGC1A or has a destabilizing effect on this protein. We then utilized molecular dynamics simulation of both the Gly482Ser variant and wild type of the PPARGC1A protein to analyze the structural changes and to reveal the conformational flexibility of the PPARGC1A protein. We observed loss flexibility in the RMSD plot of the Gly482Ser variant, which was further supported by a decrease in the SASA value in the Gly482Ser variant structure of PPARGC1A and an increase of H-bond with the increase of β-sheet and coil and decrease of turn in the DSSP plot of the Gly482Ser variant. Such alterations may significantly impact the structural conformation of the PPARGC1A protein, and it might also affect its function. It showed that the Gly482Ser variant affects the PPARGC1A structure and makes the backbone less flexible to move. In general, molecular dynamics simulation (MDS) showed more flexibility in the native PPARGC1A structure. Essential dynamics (ED) also revealed that the range of eigenvectors in the conformational space has lower extension of motion in the Gly482Ser variant compared with WT. The Gly482Ser variant also disrupts PPARGC1A interaction. Due to this single-nucleotide polymorphism in PPARGC1A, it became more rigid and might disarray the structural conformation and catalytic function of the protein and might also induce type 2 diabetes mellitus (T2DM), coronary artery disease (CAD), and nonalcoholic fatty liver disease (NAFLD). The results obtained from this study will assist wet lab research in expanding potent treatment on T2DM.

Dataset Information

Is the rs1801282 (G/C) Polymorphism of PPAR - Gamma Gene Associated with T2DM in Iraqi People?

Publications

Is the rs1801282 (G/C) Polymorphism of <i>PPAR - Gamma</i> Gene Associated with T2DM in Iraqi People?

Similar Datasets

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