Therapeutics and Clinical Risk Management (Apr 2022)

Single Nucleotide Polymorphism in the 3’ Untranslated Region of PRKAA2 on Cardiometabolic Parameters in Type 2 Diabetes Mellitus Patients Who Received Metformin

  • Virginia DM,
  • Patramurti C,
  • Fenty,
  • Setiawan CH,
  • Julianus J,
  • Hendra P,
  • Susanto NAP

Journal volume & issue
Vol. Volume 18
pp. 349 – 357

Abstract

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Dita Maria Virginia,1 Christine Patramurti,2 Fenty,1,3 Christianus Heru Setiawan,1 Jeffry Julianus,2 Phebe Hendra,1 Nicholas Adi Perdana Susanto3 1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Sanata Dharma University, Yogyakarta, Indonesia; 2Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Sanata Dharma University, Yogyakarta, Indonesia; 3Bethesda Lempuyangwangi Hospital, Yogyakarta, IndonesiaCorrespondence: Dita Maria Virginia, Universitas Sanata Dharma, Mrican, Tromol Pos 29, Yogyakarta, 55281, Indonesia, Tel +62 274 513301, Fax +62 274 562383, Email [email protected]: This study aimed to explore the association of rs857148 A>C as 3ʹUTR variants with blood pressure, HbA1c profile, and lipid profiles as cardiometabolic parameters among patients with T2DM receiving metformin.Patients and Methods: This cross-sectional analytic research was conducted with 114 consecutively selected patients with T2DM. Polymerase chain reaction-restriction fragment length polymorphism was conducted to determine rs857148. A total of 108 patients fulfilled inclusion and exclusion criteria.Results: Genotype distribution agreed with the Hardy Weinberg Equation for Equilibrium (p> 0.05) but wildtype allele was found as the minor allele. Subjects with CC genotype and C allele had enhanced HbA1c levels (OR=7.12; 95% CI=1.05– 48.26; p=0.04; OR=1.66; 95% CI=1.06– 2.60; p=0.03, respectively). It was confirmed by dominant model whereas subjects with AA tended to have reduced HbA1c compared to AC+CC genotype (OR=0.15; 95% CI=0.02– 0.97; p=0.047). AC genotype had significant correlation to total cholesterol (OR=1.05; 95% CI=1.01– 1.10; p=0.03) compared to AA genotype.Conclusion: We conclude that polymorphism of rs87148, specifically CC genotype and C allele, has a significant association with HbA1c and total cholesterol after considering oral hypoglycemia agent dose, age, gender, and combination therapy, compared to AA genotype. Future studies that involve a larger sample population and more rigorous selection criteria are required.Keywords: PRKAA2, rs857148, 3ʹUTR, cardiometabolic, type 2 diabetes mellitus

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