Genes (Jan 2020)

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

  • Sherin Bakhashab,
  • Najlaa Filimban,
  • Rana M. Altall,
  • Rami Nassir,
  • Safaa Y. Qusti,
  • Mohammed H. Alqahtani,
  • Adel M. Abuzenadah,
  • Ashraf Dallol

DOI
https://doi.org/10.3390/genes11010098
Journal volume & issue
Vol. 11, no. 1
p. 98

Abstract

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Type 2 diabetes mellitus (T2DM) is a common polygenic disease with associated comorbidities. Obesity is a major risk factor for the development of T2DM. The aim of this study is to determine the allele and genotype frequency of peroxisome proliferator-activated receptor-γ (PPARγ) rs1801282, fat mass and obesity-associated protein (FTO) rs9939609, and melanocortin 4 receptor (MC4R) rs2229616 polymorphisms and their association with risk of T2DM in the western Saudi population as mediators of adiposity phenotypes. In a cross-sectional prospective study, genomic DNA from control and T2DM patients were isolated and genotyped for these single-nucleotide polymorphisms. There was a significant association of the MC4R rs2229616 variant with T2DM, but no association with T2DM was detected with PPARγ rs1801282 or FTO rs9939609. The combination of C/C for PPARγ rs1801282, A/A for FTO rs9939609, and C/C for MC4R rs2229616 increased the risk of T2DM by 1.82. The A/T genotype for FTO rs9939609 was predicted to decrease the risk of T2DM when combined with C/C for PPARγ rs1801282 and C/C for MC4R rs2229616 or C/C for PPARγ rs1801282 and C/T MC4R rs2229616. In conclusion, our study showed the risk of the assessed variants for the development of T2DM in the Saudi population.

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