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

Abstract

Background. Transcription factor 7-like 2 gene (TCF7L2) and peroxisome proliferator-activated receptors-γ2 (PPAR-γ2) have a profound effect on the incidence of type 2 diabetes mellitus (T2DM) and had previously been found to be associated with T2DM risk in various ppopulations. However, studies in the Arab population are inconsistent. We conducted a case control study to confirm the association of variants rs10885409 of TCF7L2 and Pro12Ala (rs1801282) of PPAR-γ2 with risk of T2DM and related complications in Emirati population of Arab origin. We also investigated the interaction of these associations with obesity status. Methods. DNA was extracted from the saliva samples of 272 T2DM patients and 216 nondiabetic Emiratis. Genotyping for rs10885409 (TCF7L2) and rs1801282 (PPAR-γ2 P12A) variants was accomplished with a TaqMan assay. The subgroups were constituted according to obesity status. Results. In the nonobese group, the rs10885409 C allele in the recessive model was significantly associated with the incidence of T2DM (OR 1.975 [95% CI 1.127–3.461], P = 0.017), but this association was not observed in the obese group or when BMI was not considered. PPAR-γ2 risk allele Pro12 frequency (0.96) was similar in the groups tested and more than 90% population was homozygous for this allele. Conclusions. Our case-control study is the first of its kind in Emiratis which establishes TCF7L2 rs10885409 C allele as a T2DM risk factor in Emiratis and this association is modulated by obesity status. We also confirmed that Pro12Ala mutation in PPAR-γ2 is not associated with T2DM risk in this population.

The Effect Sizes of PPARγ rs1801282, FTO rs9939609, and MC4R rs2229616 Variants on Type 2 Diabetes Mellitus Risk among the Western Saudi Population: A Cross-Sectional Prospective Study

“…There was no association detected between this SNP and T2DM. In concordance with our study, PPARγ rs1801282 was not associated with the risk of T2DM in the Emirati population [39]. The frequencies of the PPARγ Pro12Ala genotypes were 91.9% for C/C, 8.1% for C/G and 0% for G/G in the Emirati population [39], compared to 87.3%, 11.6%, and 1.1%, respectively, in the diabetic group data in the present study.…”

“…In concordance with our study, PPARγ rs1801282 was not associated with the risk of T2DM in the Emirati population [39]. The frequencies of the PPARγ Pro12Ala genotypes were 91.9% for C/C, 8.1% for C/G and 0% for G/G in the Emirati population [39], compared to 87.3%, 11.6%, and 1.1%, respectively, in the diabetic group data in the present study. Similar to our findings here, recent studies in Iraqi and Egyptian populations reported no significant association in their cohorts with T2DM [40,41].…”

Interaction between peroxisome proliferator-activated receptor gamma polymorphism and obesity on type 2 diabetes in a Chinese Han population

“…However, Bener et al [19] suggested that no significant association between the Pro12Ala polymorphism of the PPARG2 gene and T2DM in Qatari’s population. Al-Safar et al [20] also suggested that confirmed that Pro12Ala mutation in PPARG2 is not associated with T2DM risk in this population. In a study for South Africa population, Vergotine et al [21] reported that the Pro12Ala of PPARG2 is significantly associated with insulin resistance and this polymorphism interacts with IRS1 Gly972Arg, to increase the risk of T2DM.…”

Pro12Ala PPAR-γ2 and +294T/C PPAR-δ Polymorphisms and Association with Metabolic Traits in Teenagers from Northern Mexico

“…We also found a relation between the Pro12Ala PPAR-γ2 G allele and lower glucose values (adjusted by waist circumference, sex, and age). Most studies showed no association between the polymorphism and glucose levels in other populations, such as Tunisian (adjusted by age and BMI), Cypriot, Egyptian, and Emirati populations [18,58,62,66]. Other studies have reported an association of minor allele with increased insulin [15,16].…”