Is the Rs1801282 (G/C) Polymorphism of Gene Associated with T2DM in Iraqi People?

Overview

Journal Open Access Maced J Med Sci

Specialty General Medicine

Date 2018 Apr 4

PMID 29610599

Citations 1

Authors

Amjad Hazim Al-Naemi

Akram Jarjees Ahmad

Affiliations

Soon will be listed here.

Abstract

Background: 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.

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 [(χ= 1.99, p= 0.16) and (χ= 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.

Citing Articles

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

Bakhashab S, Filimban N, Altall R, Nassir R, Qusti S, Alqahtani M Genes (Basel). 2020; 11(1).

PMID: 31947684 PMC: 7017045. DOI: 10.3390/genes11010098.

References

Schwanstecher C, Schwanstecher M . Nucleotide sensitivity of pancreatic ATP-sensitive potassium channels and type 2 diabetes. Diabetes. 2002; 51 Suppl 3:S358-62. DOI: 10.2337/diabetes.51.2007.s358. View

Mattevi V, Zembrzuski V, Hutz M . Effects of a PPARG gene variant on obesity characteristics in Brazil. Braz J Med Biol Res. 2007; 40(7):927-32. DOI: 10.1590/s0100-879x2006005000114. View

Mangelsdorf D, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K . The nuclear receptor superfamily: the second decade. Cell. 1995; 83(6):835-9. PMC: 6159888. DOI: 10.1016/0092-8674(95)90199-x. View

Mori H, Ikegami H, Kawaguchi Y, Seino S, Yokoi N, Takeda J . The Pro12 -->Ala substitution in PPAR-gamma is associated with resistance to development of diabetes in the general population: possible involvement in impairment of insulin secretion in individuals with type 2 diabetes. Diabetes. 2001; 50(4):891-4. DOI: 10.2337/diabetes.50.4.891. View

de Pablos-Velasco P, Martinez-Martin F, Rodriguez-Perez F, Ania B, Losada A, Betancor P . Prevalence and determinants of diabetes mellitus and glucose intolerance in a Canarian Caucasian population - comparison of the 1997 ADA and the 1985 WHO criteria. The Guía Study. Diabet Med. 2001; 18(3):235-41. DOI: 10.1046/j.1464-5491.2001.00451.x. View

Olefsky J . Treatment of insulin resistance with peroxisome proliferator-activated receptor gamma agonists. J Clin Invest. 2000; 106(4):467-72. PMC: 380259. DOI: 10.1172/JCI10843. View

. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010; 33 Suppl 1:S62-9. PMC: 2797383. DOI: 10.2337/dc10-S062. View

Lindi V, Sivenius K, Niskanen L, Laakso M, Uusitupa M . Effect of the Pro12Ala polymorphism of the PPAR-gamma2 gene on long-term weight change in Finnish non-diabetic subjects. Diabetologia. 2001; 44(7):925-6. DOI: 10.1007/s001250100558. View

Sugawara A, Takeuchi K, Uruno A, Ikeda Y, Arima S, Kudo M . Transcriptional suppression of type 1 angiotensin II receptor gene expression by peroxisome proliferator-activated receptor-gamma in vascular smooth muscle cells. Endocrinology. 2001; 142(7):3125-34. DOI: 10.1210/endo.142.7.8272. View

10.

Stefan N, Fritsche A, Haring H, Stumvoll M . Effect of experimental elevation of free fatty acids on insulin secretion and insulin sensitivity in healthy carriers of the Pro12Ala polymorphism of the peroxisome proliferator--activated receptor-gamma2 gene. Diabetes. 2001; 50(5):1143-8. DOI: 10.2337/diabetes.50.5.1143. View

11.

Masugi J, Tamori Y, Mori H, Koike T, Kasuga M . Inhibitory effect of a proline-to-alanine substitution at codon 12 of peroxisome proliferator-activated receptor-gamma 2 on thiazolidinedione-induced adipogenesis. Biochem Biophys Res Commun. 2000; 268(1):178-82. DOI: 10.1006/bbrc.2000.2096. View

12.

Wildman R, Gu D, Reynolds K, Duan X, He J . Appropriate body mass index and waist circumference cutoffs for categorization of overweight and central adiposity among Chinese adults. Am J Clin Nutr. 2004; 80(5):1129-36. DOI: 10.1093/ajcn/80.5.1129. View

13.

Badii R, Bener A, Zirie M, Al-Rikabi A, Simsek M, Al-Hamaq A . Lack of association between the Pro12Ala polymorphism of the PPAR-gamma 2 gene and type 2 diabetes mellitus in the Qatari consanguineous population. Acta Diabetol. 2007; 45(1):15-21. DOI: 10.1007/s00592-007-0013-8. View

14.

Meshkani R, Taghikhani M, Larijani B, Bahrami Y, Khatami S, Khoshbin E . Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPARgamma-2) gene is associated with greater insulin sensitivity and decreased risk of type 2 diabetes in an Iranian population. Clin Chem Lab Med. 2007; 45(4):477-82. DOI: 10.1515/CCLM.2007.095. View

15.

Mancini F, Vaccaro O, Sabatino L, Tufano A, Rivellese A, Riccardi G . Pro12Ala substitution in the peroxisome proliferator-activated receptor-gamma2 is not associated with type 2 diabetes. Diabetes. 1999; 48(7):1466-8. DOI: 10.2337/diabetes.48.7.1466. View

16.

Thorsby P, Midthjell K, Gjerlaugsen N, Holmen J, Hanssen K, Birkeland K . Comparison of genetic risk in three candidate genes (TCF7L2, PPARG, KCNJ11) with traditional risk factors for type 2 diabetes in a population-based study--the HUNT study. Scand J Clin Lab Invest. 2008; 69(2):282-7. DOI: 10.1080/00365510802538188. View

17.

Knowler W, Pettitt D, Saad M, BENNETT P . Diabetes mellitus in the Pima Indians: incidence, risk factors and pathogenesis. Diabetes Metab Rev. 1990; 6(1):1-27. DOI: 10.1002/dmr.5610060101. View

18.

Tachibana K, Kobayashi Y, Tanaka T, Tagami M, Sugiyama A, Katayama T . Gene expression profiling of potential peroxisome proliferator-activated receptor (PPAR) target genes in human hepatoblastoma cell lines inducibly expressing different PPAR isoforms. Nucl Recept. 2005; 3:3. PMC: 1262764. DOI: 10.1186/1478-1336-3-3. View

19.

Sramkova D, Kunesova M, Hainer V, Hill M, Vcelak J, Bendlova B . Is a Pro12Ala polymorphism of the PPARgamma2 gene related to obesity and type 2 diabetes mellitus in the Czech population?. Ann N Y Acad Sci. 2002; 967:265-73. DOI: 10.1111/j.1749-6632.2002.tb04282.x. View

20.

Sanghera D, Demirci F, Been L, Ortega L, Ralhan S, Wander G . PPARG and ADIPOQ gene polymorphisms increase type 2 diabetes mellitus risk in Asian Indian Sikhs: Pro12Ala still remains as the strongest predictor. Metabolism. 2009; 59(4):492-501. PMC: 2843807. DOI: 10.1016/j.metabol.2009.07.043. View