Association between PRO12ALA polymorphism of the PPAR-γ2 gene and type 2 diabetes mellitus in Iranian patients

Abstract

BACKGROUND:Peroxisome proliferator-activated receptor (PPARs) have been identified as ligand-activated transcription factors that belong to the nuclear receptor superfamily. It has been shown that an association exists between Proline 12 alanine (Pro12Ala) polymorphism of PPAR-GAMMA2 (PPAR-γ2) gene and increased risk of type 2 diabetes mellitus (T2DM) in different populations. Therefore, the present study was designed to investigate the association between Pro12Ala polymorphism of PPAR-γ2 gene and T2DM in an Iranian population.MATERIALS AND METHODS:Two hundred unrelated people, including 100 healthy controls and 100 diabetic patients were recruited diagnosed based on American Diabetes Association criteria. Blood samples were used for isolation of genomic deoxyribonucleic acid (DNA). Having extracted the genomic DNA from human blood leukocytes by means of High Pure polymerase chain reaction (PCR) Template preparation kit, we carried out polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on each blood sample. Then, Genomic DNA was digested by BstU-I restriction enzyme. Thereafter, restriction products were analyzed by means of Polyacrylamide gel electrophoresis and stained by Ethidium Bromide.RESULTS:We found that the frequency of Ala allele in healthy subjects was significantly higher than in diabetic subjects (P = 0003). Moreover, the genotype frequency of Ala/Ala in healthy subjects was significantly higher than in diabetic subjects (P < 0.001). However, the genotype frequency of Ala/Pro in diabetic subjects was significantly higher than in healthy subjects (P < 0.001).CONCLUSION:The present study suggests that polymorphism of PPAR-γ2 gene is associated with T2DM. Furthermore, Ala allele is significantly found in non-diabetic individual’s Iranian population.

Association of the Genetic Polymorphisms in Transcription Factor 7-Like 2 and Peroxisome Proliferator-Activated Receptors-γ2 with Type 2 Diabetes Mellitus and Its Interaction with Obesity Status in Emirati Population

“…TCF7L2 variant rs7903146 a C-to-T (genomic position: 114748339) substitution in intron 3 and PPAR-γ2 Pro12Ala have been most extensively studied in all major ethnic groups and were found to be more consistently associated with the risk of developing T2DM in most of populations, such as Asians, Africans, and Caucasians [ 12 , 13 ]. These associations were also observed in most of the Arab populations of MENA region like Tunisians, Lebanese, [ 14 – 18 ], Iranian [ 19 , 20 ], and North Africans [ 21 ]. Although these polymorphisms were established as risk factor for T2DM in most of the populations studied so far, however, some of the studied polymorphisms seem not to be a major contributor to T2DM susceptibility in the Saudi and Emirati Arab populations [ 22 – 24 ].…”

Association between Genetic Variants and Diabetes Mellitus in Iranian Populations: A Systematic Review of Observational Studies

“…Association of Pro12Ala polymorphism of PPAR γ with T2DM was investigated in three studies [ 41 , 69 , 75 ]. Negative significant association of Ala/Ala genotype with T2DM was observed in two studies ( P = 0.003) [ 41 , 75 ].…”

“…Association of Pro12Ala polymorphism of PPAR γ with T2DM was investigated in three studies [ 41 , 69 , 75 ]. Negative significant association of Ala/Ala genotype with T2DM was observed in two studies ( P = 0.003) [ 41 , 75 ]. Ala/Pro carriers were shown to be positively associated in one study [ 41 ] and negatively associated in another study [ 75 ] with T2DM ( P < 0.001 and P = 0.003, resp.).…”

<p>Type 2 Diabetes-Associated Genetic Polymorphisms as Potential Disease Predictors</p>

“…59,193 Motavallian et al compared the allele distributions of Pro12Ala polymorphism between healthy individuals and those with diabetes. 188 They found a higher frequency of the Ala allele12 in healthy individuals than in patients with diabetes. Another study found a protective role of high Ala frequency against T2DM as it was associated with increased insulin sensitivity, while low frequency of the Ala12 allele was associated with decreased insulin sensitivity (insulin resistance), which may lead to diabetes.…”

“…187 The PPARγ2 gene plays roles in glucose homeostasis, lipid metabolism, obesity, insulin sensitivity, T2DM, and various adipocytespecific genes. 59,[188][189][190] Based on several case-control and family-based studies, estimated that Pro12 allele (ie, the major allele) of PPARγ was associated with a 1.25-fold elevated risk of T2DM. 191 Further, the study of Chan et al showed that the Pro12Ala polymorphism was associated with T2DM risk in the multiethnic Women's Health Initiative (WHI) Observational Study at a nominal significance level (Pro12 allele is the risk-increasing allele, p=0.01, additive model).…”