Research Article


DOI :10.26650/experimed.1382282   IUP :10.26650/experimed.1382282    Full Text (PDF)

Peroxisome Proliferator-activated Receptor-alpha (PPARA) and – Gamma (PPARG) Polymorphisms as Risk Factors for Dyslipidemia and MetS in Turkish Adults

Filiz Güçlü GeyikEvrim Kömürcü BayrakGünay CanNihan Erginel Ünaltuna

Objective: Dyslipidemia and metabolic syndrome (MetS) are complex diseases affected by environmental factors such as lifestyle and genetic predisposition. The genes encoding peroxisome proliferator-activated receptor-gamma (PPARG) and alpha (PPARA) are crucial in the development of dyslipidemia and MetS. We aimed to investigate the relation of these genes with dyslipidemia and MetS in the Turkish adult population.

Materials and Methods: The Turkish Adult Risk Factor (TARF-TEKHARF) cohort was randomly selected, and a cross-sectional analysis was performed. The PPARA rs1800206 C>G genotypes were determined in a sample of 339 unrelated Turkish adults by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and 12% polyacrylamide gel electrophoresis (PAGE) methods. The PPARG rs1801282 C>G genotypes were determined in a sample of 436 unrelated Turkish adults by a PCR-RFLP method.

Results: Both single nucleotide polymorphisms (SNPs) minor alleles were related to a risk of dyslipidemia. Logistic regression analysis showed a significantly increased risk for dyslipidemia in G allele carriers of rs1800206 C>G (Odds Ratio (OR)= 3.26; 95% CI= 1.16-9.12), and in G risk allele carriers of rs1801282 (OR= 1.85; 95% CI= 1.07-3.19), after adjustment for age, gender, lipid-lowering medication usage, physical activity and smoking status. Regarding MetS risk in the TARF study group, the G-allele of rs1800206 PPARA gene exhibited a significant OR of 3.75, after adjustment for gender, age, smoking status, and physical activity.

Conclusion: The G alleles of the studied SNPs in the PPARA and PPARG genes are related to increased dyslipidemia risk. Furthermore, The G allele of the PPARA gene is related to increased MetS risk.


PDF View

References

  • 1. Hildrum B, Mykletun A, Hole T, Midthjell K, Dahl AA. Age-specific prevalence of the metabolic syndrome defined by the International Diabetes Federation and the National Cholesterol Education Program: the Norwegian HUNT 2 study. BMC Public Health 2007; 7: 220. google scholar
  • 2. Ge H, Yang Z, Li X, Liu D, Li Y, Pan Y, et al. The prevalence and associated factors of metabolic syndrome in Chinese aging population. Sci Rep 2020; 10(1): 20034. google scholar
  • 3. Milionis HJ, Elisaf MS, Mikhailidis DP. Lipid abnormalities and cardiovascular risk in the elderly. Curr Med Res Opin 2008; 24(3): 653-7. google scholar
  • 4. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 2002; 287(3): 356-9. google scholar
  • 5. Despres JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature 2006; 444(7121): 881-7. google scholar
  • 6. Bosy-Westphal A, Onur S, Geisler C, Wolf A, Korth O, Pfeuffer M, et al. Common familial influences on clustering of metabolic syndrome traits with central obesity and insulin resistance: the Kiel obesity prevention study. Int J Obes (Lond) 2007; 31(5): 784-90. google scholar
  • 7. Grundy SM, Hansen B, Smith SC Jr, Cleeman JI, Kahn RA, American Heart A, et al. Clinical management of metabolic syndrome: report of the American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association conference on scientific issues related to management. Arterioscler Thromb Vasc Biol 2004; 24(2): e19-24. google scholar
  • 8. Onat A, Hergenc G, Turkmen S, Yazici M, Sari I, Can G. Discordance between insulin resistance and metabolic syndrome: features and associated cardiovascular risk in adults with normal glucose regulation. Metabolism 2006; 55(4): 445-52. google scholar
  • 9. Braissant O, Foufelle F, Scotto C, Dauca M, Wahli W. Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology 1996; 137(1): 354-66. google scholar
  • 10. Tugwood JD, Issemann I, Anderson RG, Bundell KR, Mcpheat WL, Green S. The mouse peroxisome proliferator activated receptor recognizes a response element in the 5’ flanking sequence of the rat acyl coa oxidase gene. Embo Journal 1992; 11(2): 433-9. google scholar
  • 11. Sher T, Yi HF, McBride OW, Gonzalez FJ. cDNA cloning, chromosomal mapping, and functional characterization of the human peroxisome proliferator activated receptor. Biochemistry 1993; 32(21): 5598-604. google scholar
  • 12. Xu J, Xiao G, Trujillo C, Chang V, Blanco L, Joseph SB, et al. Peroxisome proliferator-activated receptor alpha (PPARalpha) influences substrate utilization for hepatic glucose production. J Biol Chem 2002; 277(52): 50237-44. google scholar
  • 13. Leone TC, Weinheimer CJ, Kelly DP. A critical role for the peroxisome proliferator-activated receptor alpha (PPARalpha) in the cellular fasting response: the PPARalpha-null mouse as a model of fatty acid oxidation disorders. Proc Natl Acad Sci USA 1999; 96(13): 7473-8. google scholar
  • 14. Lefebvre P, Chinetti G, Fruchart JC, Staels B. Sorting out the roles of PPAR alpha in energy metabolism and vascular homeostasis. J Clin Invest 2006; 116(3): 571-80. google scholar
  • 15. Carmona MC, Louche K, Lefebvre B, Pilon A, Hennuyer N, Audinot-Bouchez V, et al. S 26948: a new specific peroxisome proliferator activated receptor gamma modulator with potent antidiabetes and antiatherogenic effects. Diabetes 2007; 56(11): 2797-808. google scholar
  • 16. Burns KA, Vanden Heuvel JP. Modulation of PPAR activity via phosphorylation. Biochim Biophys Acta 2007; 1771(8): 952-60. google scholar
  • 17. Deeb SS, Fajas L, Nemoto M, Pihlajamaki J, Mykkanen L, Kuusisto J, et al. A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet 1998; 20(3): 284-7. google scholar
  • 18. Ek J, Andersen G, Urhammer SA, Hansen L, Carstensen B, Borch-Johnsen K, et al. Studies of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) gene in relation to insulin sensitivity among glucose tolerant caucasians. Diabetologia 2001; 44(9): 1170-6. google scholar
  • 19. Sapone A, Peters JM, Sakai S, Tomita S, Papiha SS, Dai R, et al. The human peroxisome proliferator-activated receptor alpha gene: identification and functional characterization of two natural allelic variants. Pharmacogenetics 2000; 10(4): 321-33. google scholar
  • 20. Vohl MC, Lepage P, Gaudet D, Brewer CG, Betard C, Perron P, et al. Molecular scanning of the human PPAR alpha gene: association of the L162V mutation with hyperapobetalipoproteinemia. J Lipid Res 2000; 41(6): 945-52. google scholar
  • 21. Flavell DM, Torra IP, Jamshidi Y, Evans D, Diamond JR, Elkeles RS, et al. Variation in the PPAR alpha gene is associated with altered function in vitro and plasma lipid concentrations in Type II diabetic subjects. Diabetologia 2000; 43(5): 673-80. google scholar
  • 22. Flavell DM, Jamshidi Y, Hawe E, Pineda Torra I, Taskinen MR, Frick MH, et al. Peroxisome proliferator-activated receptor alpha gene variants influence progression of coronary atherosclerosis and risk of coronary artery disease. Circulation 2002; 105(12): 1440-5. google scholar
  • 23. Sarhangi N, Sharifi F, Hashemian L, Hassani Doabsari M, Heshmatzad K, Rahbaran M, et al. PPARG (Pro12Ala) genetic variant and risk of T2DM: a systematic review and meta-analysis. Sci Rep 2020; 10(1): 12764. google scholar
  • 24. Mazzotti DR, Singulane CC, Ota VK, Rodrigues TP, Furuya TK, de Souza FJ, et al. PPARalpha polymorphisms as risk factors for dyslipidemia in a Brazilian population. Mol Genet Metab 2011; 102(2): 189-93. google scholar
  • 25. Li S, He C, Nie H, Pang Q, Wang R, Zeng Z, et al. G Allele of the rs1801282 polymorphism in PPARgamma gene confers an increased risk of obesity and hypercholesterolemia, while T allele of the rs3856806 polymorphism displays a protective role against dyslipidemia: a systematic review and meta-analysis. Front Endocrinol (Lausanne) 2022; 13: 919087. google scholar
  • 26. Gu SJ, Liu MM, Guo ZR, Wu M, Chen Q, Zhou ZY, et al. Gene-gene interactions among PPARalpha/delta/gamma polymorphisms for hypertriglyceridemia in Chinese Han population. Gene 2013; 515(2): 272-6. google scholar
  • 27. Gu SJ, Guo ZR, Zhou ZY, Hu XS, Wu M, Zhang N. Peroxisome proliferator-activated receptor gamma polymorphisms as risk factors for dyslipidemia. Mol Med Rep 2014; 10(5): 2759-63. google scholar
  • 28. Gu SJ, Guo ZR, Zhou ZY, Hu XS, Wu M. PPAR alpha and PPAR gamma polymorphisms as risk factors for dyslipidemia in a Chinese Han population. Lipids Health Dis. 2014; 13: 23. google scholar
  • 29. Robitaille J, Brouillette C, Houde A, Lemieux S, Perusse L, Tchernof A, et al. Association between the PPARalpha-L162V polymorphism and components of the metabolic syndrome. J Hum Genet 2004; 49(9): 482-9. google scholar
  • 30. Bage IJ, Kamalanathan S, Selvarajan S, Sahoo J, Mathaiyan J, Naik D. Peroxisome proliferator-activated receptor alpha and gamma gene polymorphisms among South Indian patients with diabetic dyslipidaemia. Indian J Endocrinol Metab 2023; 27(2): 118-26. google scholar
  • 31. Chia PP, Fan SH, Say YH. Screening of peroxisome proliferator-activated receptors (PPARs) alpha, gamma and alpha gene polymorphisms for obesity and metabolic syndrome association in the multi-ethnic Malaysian population. Ethn Dis 2015; 25(4): 383-90. google scholar
  • 32. Mousavinasab F, Tahtinen T, Jokelainen J, Koskela P, Vanhala M, Oikarinen J, et al. The Pro12Ala polymorphism of the PPAR gamma 2 gene influences sex hormone-binding globulin level and its relationship to the development of the metabolic syndrome in young Finnish men. Endocrine 2006; 30(2): 185-90. google scholar
  • 33. Rhee EJ, Oh KW, Lee WY, Kim SY, Oh ES, Baek KH, et al. Effects of two common polymorphisms of peroxisome proliferator-activated receptor-gamma gene on metabolic syndrome. Arch Med Res 2006; 37(1): 86-94. google scholar
  • 34. Smalinskiene A, Petkeviciene J, Luksiene D, Jureniene K, Klumbiene J, Lesauskaite V. Association between APOE, SCARB1, PPARalpha polymorphisms and serum lipids in a population of Lithuanian adults. Lipids Health Dis 2013; 12: 120. google scholar
  • 35. Onat A. Risk factors and cardiovascular disease in Turkey. Atherosclerosis 2001; 156(1): 1-10. google scholar
  • 36. Guclu-Geyik F, Coban N, Can G, Erginel-Unaltuna N. The rs2175898 polymorphism in the ESR1 Gene has a significant sex-specific effect on obesity. Biochem Genet 2020; 58(6): 935-952. google scholar
  • 37. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of The National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 2001; 285(19): 2486-97. google scholar
  • 38. American Diabetes Association. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2020. Diabetes Care 2020; 43(Suppl 1): S14-31. google scholar
  • 39. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 2003; 26 Suppl 1: S5-20. google scholar
  • 40. Yen CJ, Beamer BA, Negri C, Silver K, Brown KA, Yarnall DP, et al. Molecular scanning of the human peroxisome proliferator activated receptor gamma (hPPAR gamma) gene in diabetic Caucasians: identification of a Pro12Ala PPAR gamma 2 missense mutation. Biochem Biophys Res Commun 1997; 241(2): 270-4. google scholar
  • 41. Schoonjans K, Staels B, Auwerx J. Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression. J Lipid Res 1996; 37(5): 907-25. google scholar
  • 42. Sparso T, Hussain MS, Andersen G, Hainerova I, Borch-Johnsen K, Jorgensen T, et al. Relationships between the functional PPARalpha Leu162Val polymorphism and obesity, type 2 diabetes, dyslipidaemia, and related quantitative traits in studies of 5799 middle-aged white people. Mol Genet Metab 2007; 90(2): 205-9. google scholar
  • 43. Uthurralt J, Gordish-Dressman H, Bradbury M, Tesi-Rocha C, Devaney J, Harmon B, et al. PPARalpha L162V underlies variation in serum triglycerides and subcutaneous fat volume in young males. BMC Med Genet 2007; 8:55. google scholar
  • 44. Barbieri M, Rizzo MR, Papa M, Acampora R, De Angelis L, Olivieri F, et al. Role of interaction between variants in the PPARG and interleukin-6 genes on obesity related metabolic risk factors. Exp Gerontol 2005; 40(7): 599-604. google scholar
  • 45. Iwata E, Matsuda H, Fukuda T, Fukuen S, Motomura T, Igarashi T, et al. Mutations of the peroxisome proliferator-activated receptor gamma (PPAR gamma) gene in a Japanese population: the Pro12Ala mutation in PPAR gamma 2 is associated with lower concentrations of serum total and non-HDL cholesterol. Diabetologia 2001; 44(10): 1354-5. google scholar
  • 46. Tellechea ML, Aranguren F, Perez MS, Cerrone GE, Frechtel GD, Taverna MJ. Pro12Ala polymorphism of the peroxisome proliferatoractivated receptor-gamma gene is associated with metabolic syndrome and surrogate measures of insulin resistance in healthy men: interaction with smoking status. Circ J 2009; 73(11): 2118-24. google scholar
  • 47. Robitaille J, Despres JP, Perusse L, Vohl MC. The PPAR-gamma P12A polymorphism modulates the relationship between dietary fat intake and components of the metabolic syndrome: results from the Quebec Family Study. Clin Genet 2003; 63(2): 109-16. google scholar
  • 48. Meirhaeghe A, Amouyel P. Impact of genetic variation of PPARgamma in humans. Mol Genet Metab 2004; 83(1-2): 93-102. google scholar
  • 49. Yang LL, Hua Q, Liu RK, Yang Z. Association between two common polymorphisms of PPARgamma gene and metabolic syndrome families in a Chinese population. Arch Med Res 2009; 40(2): 89-96. google scholar
  • 50. Montagnana M, Fava C, Nilsson PM, Engstrom G, Hedblad B, Lippi G, et al. The Pro12Ala polymorphism of the PPARG gene is not associated with the metabolic syndrome in an urban population of middle-aged Swedish individuals. Diabet Med 2008; 25(8): 902-8. google scholar
  • 51. Zhang R, Wang J, Yang R, Sun J, Chen R, Luo H, et al. Effects of Pro12Ala polymorphism in peroxisome proliferator-activated receptor-gamma2 gene on metabolic syndrome risk: a meta-analysis. Gene 2014; 535(1): 79-87. google scholar

Citations

Copy and paste a formatted citation or use one of the options to export in your chosen format


EXPORT



APA

Güçlü Geyik, F., Kömürcü Bayrak, E., Can, G., & Ünaltuna, N.E. (2023). Peroxisome Proliferator-activated Receptor-alpha (PPARA) and – Gamma (PPARG) Polymorphisms as Risk Factors for Dyslipidemia and MetS in Turkish Adults. Experimed, 13(3), 281-289. https://doi.org/10.26650/experimed.1382282


AMA

Güçlü Geyik F, Kömürcü Bayrak E, Can G, Ünaltuna N E. Peroxisome Proliferator-activated Receptor-alpha (PPARA) and – Gamma (PPARG) Polymorphisms as Risk Factors for Dyslipidemia and MetS in Turkish Adults. Experimed. 2023;13(3):281-289. https://doi.org/10.26650/experimed.1382282


ABNT

Güçlü Geyik, F.; Kömürcü Bayrak, E.; Can, G.; Ünaltuna, N.E. Peroxisome Proliferator-activated Receptor-alpha (PPARA) and – Gamma (PPARG) Polymorphisms as Risk Factors for Dyslipidemia and MetS in Turkish Adults. Experimed, [Publisher Location], v. 13, n. 3, p. 281-289, 2023.


Chicago: Author-Date Style

Güçlü Geyik, Filiz, and Evrim Kömürcü Bayrak and Günay Can and Nihan Erginel Ünaltuna. 2023. “Peroxisome Proliferator-activated Receptor-alpha (PPARA) and – Gamma (PPARG) Polymorphisms as Risk Factors for Dyslipidemia and MetS in Turkish Adults.” Experimed 13, no. 3: 281-289. https://doi.org/10.26650/experimed.1382282


Chicago: Humanities Style

Güçlü Geyik, Filiz, and Evrim Kömürcü Bayrak and Günay Can and Nihan Erginel Ünaltuna. Peroxisome Proliferator-activated Receptor-alpha (PPARA) and – Gamma (PPARG) Polymorphisms as Risk Factors for Dyslipidemia and MetS in Turkish Adults.” Experimed 13, no. 3 (Dec. 2024): 281-289. https://doi.org/10.26650/experimed.1382282


Harvard: Australian Style

Güçlü Geyik, F & Kömürcü Bayrak, E & Can, G & Ünaltuna, NE 2023, 'Peroxisome Proliferator-activated Receptor-alpha (PPARA) and – Gamma (PPARG) Polymorphisms as Risk Factors for Dyslipidemia and MetS in Turkish Adults', Experimed, vol. 13, no. 3, pp. 281-289, viewed 4 Dec. 2024, https://doi.org/10.26650/experimed.1382282


Harvard: Author-Date Style

Güçlü Geyik, F. and Kömürcü Bayrak, E. and Can, G. and Ünaltuna, N.E. (2023) ‘Peroxisome Proliferator-activated Receptor-alpha (PPARA) and – Gamma (PPARG) Polymorphisms as Risk Factors for Dyslipidemia and MetS in Turkish Adults’, Experimed, 13(3), pp. 281-289. https://doi.org/10.26650/experimed.1382282 (4 Dec. 2024).


MLA

Güçlü Geyik, Filiz, and Evrim Kömürcü Bayrak and Günay Can and Nihan Erginel Ünaltuna. Peroxisome Proliferator-activated Receptor-alpha (PPARA) and – Gamma (PPARG) Polymorphisms as Risk Factors for Dyslipidemia and MetS in Turkish Adults.” Experimed, vol. 13, no. 3, 2023, pp. 281-289. [Database Container], https://doi.org/10.26650/experimed.1382282


Vancouver

Güçlü Geyik F, Kömürcü Bayrak E, Can G, Ünaltuna NE. Peroxisome Proliferator-activated Receptor-alpha (PPARA) and – Gamma (PPARG) Polymorphisms as Risk Factors for Dyslipidemia and MetS in Turkish Adults. Experimed [Internet]. 4 Dec. 2024 [cited 4 Dec. 2024];13(3):281-289. Available from: https://doi.org/10.26650/experimed.1382282 doi: 10.26650/experimed.1382282


ISNAD

Güçlü Geyik, Filiz - Kömürcü Bayrak, Evrim - Can, Günay - Ünaltuna, NihanErginel. Peroxisome Proliferator-activated Receptor-alpha (PPARA) and – Gamma (PPARG) Polymorphisms as Risk Factors for Dyslipidemia and MetS in Turkish Adults”. Experimed 13/3 (Dec. 2024): 281-289. https://doi.org/10.26650/experimed.1382282



TIMELINE


Submitted27.10.2023
Accepted01.12.2023
Published Online28.12.2023

LICENCE


Attribution-NonCommercial (CC BY-NC)

This license lets others remix, tweak, and build upon your work non-commercially, and although their new works must also acknowledge you and be non-commercial, they don’t have to license their derivative works on the same terms.


SHARE




Istanbul University Press aims to contribute to the dissemination of ever growing scientific knowledge through publication of high quality scientific journals and books in accordance with the international publishing standards and ethics. Istanbul University Press follows an open access, non-commercial, scholarly publishing.