Original ArticleOpen Access

Relationship Between the Paraoxonase 1 Gene Glutamine 192 to Arginine Polymorphism and Diabetes Mellitus in Ghanaian Subjects

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DOI: 10.23958/ijirms/vol10-i07/2112· Pages: 280 - 284· Vol. 10, No. 07, (2025)· Published: July 28, 2025
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Abstract

Introduction: The activity of human Paraoxonase 1 (PON1), an HDL-associated enzyme with anti-atherogenic properties, has been observed to be reduced in a number of diseases, including diabetes. This has partly been attributed to a PON1 Glutamine (Q)/Arginine (R) polymorphism at codon 192 of the PON1 gene. Aim: To determine the prevalence of PON1 Q192R polymorphism in Ghanaian patients with type 2 diabetes (T2DM), and it impact on lipid profiles of T2DM subjects. Methods: PON1 Q192R was genotyped in 112 individuals with type 2 diabetes mellitus (T2DM) and 97 nondiabetic control individuals, using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) analysis. Other investigations determined using standard methods included fasting blood glucose (FPG), body mass index (BMI), lipid profile, atherogenic indices and hip-waist ratios. Results: The PON1 RR genotype found to be was the most common in both T2DM patients (74.6 %) and controls (57.1 %), whilst the QR genotype was the least frequent in both groups (7.3 % and 9.5% for T2DM and controls respectively). These genotype distributions were however not significantly different between the study groups. Allele frequencies in T2DM and the control groups were significantly different, with R allele being the most common in both T2DM patients and controls. The R allele was found to be increased in T2DM. The Q192R genotype does not consistently affect the lipid and lipoprotein concentrations of T2DM and healthy populations. Conclusion: The RR genotype was the most predominant in T2DM patients and healthy individuals within a Ghanaian population. The prevalence of the R allele in T2DM may have implications for the metabolism of oxidized lipoproteins as these oxidative modifications are central to the development of cardiovascular disease in T2DM.

Keywords

alleleGhanaiandiabetes mellitusparaoxonase 192 gene polymorphismparaoxonase 1

References

  1. Mackness MI, Mackness B, Durrington PN, et al.: Paraoxonase: Biochemistry, genetics, and relationship to plasma lipoproteins. Cur. Opin. Lipidol. 1996, 7:69-76. 10.1097/00041433-199604000-00004DOI ↗Google Scholar ↗
  2. Montella IR, Schama R, Valle D: The classification of esterases: An important gene family involved in insecticide resistance. A review. Mem Inst Oswaldo Cruz. 2012, 107:437-49. 10.1590/s0074-02762012000400001DOI ↗Google Scholar ↗
  3. Costa C, Gangemi S, Giambò F, et al.: Oxidative stress biomarkers and paraoxonase 1 polymorphism frequency in farmers occupationally exposed to pesticides. Mol Med Rep. 2015, 12:6353-6357. 10.3892/mmr.2015.4196DOI ↗Google Scholar ↗
  4. Sharma GS, Kumar T, Singh LR: N-homocysteinylation induces different structural and functional consequences on acidic and basic proteins. PLoS One. 2014, 9:1163. 10.1371/journal.pone.0116386DOI ↗Google Scholar ↗
  5. Costa LG, Vitalone A, Cole TB, and Furlong CE: Modulation of paraoxonase (PON1) activity. Biochem. Pharmacol. 2005, 69:541-550.Google Scholar ↗
  6. Durrington PN, Mackness B, Mackness MI: The hunt for nutritional and pharmacological modulators of paraoxonase. Arterioscler. Thromb. Vasc. Biol. 2002, 22:1248-1250.Google Scholar ↗
  7. Wysocka A Zwolak A: The Relevance of non-coding DNA variations of Paraoxonase gene cluster in 5 of 6: Atherosclerosis-related diseases. Int. J. Mol. Sci. 2021, 22:2137.Google Scholar ↗
  8. Levy D, Reichert CO, Bydlowski SP: Paraoxonases Activities and Polymorphisms in Elderly and Old-Age Diseases: An Overview. Antioxidants. 2019, 8:118.Google Scholar ↗
  9. Leviev I, James RW: Promoter polymorphisms of human paraoxonase PON 1 gene and serum paraoxonase activities and concentrations. Arterioscler. Thromb. Vasc. Biol. 2000, 20:516-521. 10.1161/01.ATV.20.2.516DOI ↗Google Scholar ↗
  10. Mahsa A, Sedigheh EB, Amir A, et al.: Paraoxonase-1 Q192R polymorphism and its association with hs-CRP and fasting blood glucose levels and risk of coronary artery disease. Diabetes Metab. Syndr. 2019, 13:1053-1057.Google Scholar ↗
  11. Flekac M, Skrha J, Zidkova K, Lacinova Z, Hilgertova J: Paraoxonase1 gene polymorphisms and enzyme activities in diabetes mellitus. Physiol. Res. 2008, 57:717-726. 10.33549/physiolres.931285DOI ↗Google Scholar ↗
  12. Abbot CA, Mackness, MI, Kumar S: Serum Paraoxonase activity, concentration, and phenotype distribution in diabetes mellitus in relation to serum lipids and lipoproteins. Thromb. Vasc. Biol. 1995, 15:1812. 10.1161/01.atv.15.11.1812DOI ↗Google Scholar ↗
  13. Wild S, Roglic G, Sicree R, King H: Global prevalence of Diabetes estimates for the year 2000 and projections. for. 20302004, 27:1047-1053. 10.2337/diacare.27.5.1047DOI ↗Google Scholar ↗
  14. Tuomilehto J, Lindstrom J, Eriksson JG, et al.: Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N. Engl. J. Med. 2001, 344:1343-1350. 10.1056/NEJM200105033441801DOI ↗Google Scholar ↗
  15. Karakaya P. Ozdemir B. Mert M. Okuturlar Y: Relation of Paraoxonase 1 Activity with Biochemical Variables, Brachial Artery Intima-Media Thickness in Patients with Diabetes with or without Obesity. Obes Facts. 2018, 11:56-66.Google Scholar ↗
  16. Tward A, Xia YR, Wang XP, et al.: Decreased atherosclerotic lesion formation in human serum paraoxonase transgenic mice. Circulation. 2002, 23:484-90. 10.1161/01.ATV.0000222924.62641.aaDOI ↗Google Scholar ↗
  17. Mackness B, Quarck R, Verreth W, et al.: Human paraoxonase 1 over-expression inhibits atherosclerosis in a mouse model of metabolic syndrome. Arterioscler. Thromb. Vasc. Biol. 2006, 26:1545-1550. 10.1161/01.ATV.0000222924. 62641.aaDOI ↗Google Scholar ↗
  18. WHO: Definition, diagnosis and classification of diabetes mellitus and its complications: Report of a WHO consultation. Part 1, Diagnosis and classification of diabetes mellitus. World Health Organization. 1999Google Scholar ↗
  19. Friedewald WT, Levy RI, Fredrickson DS: Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972, 18:499-502.Google Scholar ↗
  20. Mackness MI, Mackness B, Durrington PN, et al.: Paraoxonase and coronary heart disease. Curr Opin Lipidol. 1998, 9:319-24. 10.1097/00041433-199808000-00006DOI ↗Google Scholar ↗
  21. Bounafaa A, Berrougui H, Ghalim N, et al.: Association between Paraoxonase 1 (PON1) Polymorphisms and the Risk of Acute Coronary Syndrome in a North African Population. PLoS ONE. 2015, 10:0133719.Google Scholar ↗
  22. Draganov DI, La Du BN: Pharmacogenetics of paraoxonases: a brief review. Naunyn Schmiedebergs Arch Pharmacol. 2004, 69:78-88.Google Scholar ↗
  23. Khodier SA, Abd El Raouf YM, Amer AE, et al.: Paraoxonase gene polymorphism and activity in type 2 diabetes mellitus with microvascular complications. J. Amer. Sci. 2012, 8:303-309. 10.1007/s00210-003-0833-1DOI ↗Google Scholar ↗
  24. El Fasakhany FM, El-Segay O, Alahwal L, et al.: Paraoxonse 1 activity and paraoxonase 192 gene polymorphism in non-insulin dependent diabetes mellitus patients among Egyptian population. Tanta Med Sci J. 2007, 2:68-77.Google Scholar ↗
  25. Agachan B, Yilmaz H, Karaali Z, et al.: Paraoxonase 55 and 192 polymorphism and its relationship to serum paraoxonase activity and serum lipids in Turkish patients with non-insulin dependent diabetes mellitus. Cell Biochem Funct. 2004, 22:163-8. 10.1002/cbf.1070.DOI ↗Google Scholar ↗
Author details
Nii A. Aryee
Department of Medical Biochemistry, UGMS, University of Ghana, Accra, Ghana.
✉ Corresponding Author
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Steve A. Asante-Poku
Department of Medical Biochemistry, UGMS, University of Ghana, Accra, Ghana.
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Emmanuel A. Tagoe
Medical Laboratory Science, SBHAS, University of Ghana, Accra, Ghana.
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Grace K. Ababio
Department of Medical Biochemistry, UGMS, University of Ghana, Accra, Ghana.
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Dorcas A. Muhyia Annan
Department of Vascular Biology and Molecular Pathology, Hokkaido University, Kita-Ku, Sapporo, Japan.
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