Association between Three Variants in the PRKAA2 gene, rs2796498, rs9803799, and rs2746342, with 10-year ASCVD Risk on Newly Diagnosed T2DM in Yogyakarta, Indonesia

BACKGROUND: AMPK has pivotal roles in glucose and lipid metabolism, including  AMPKa2, which PRKAA2 encodes. Metformin as an anti-hyperglycemia agent acts through AMPK. Poor glycemia control among patients with type 2 diabetes mellitus (T2DM) could increase atherosclerosis cardiovascular disease (ASCVD) risk. Therefore, PRKAA2 genetic variation might contribute to 10-year ASCVD risk in patients with newly diagnosed T2DM receiving monotherapy metformin. AIM: The study aimed to detect an association between PRKAA2 genetic variation with 10 year-ASCVD risk among newly diagnosed T2DM patients prescribed monotherapy metformin. METHODS: This present study was a case-control study involving 107 participants. Analysis of PRKAA2 genetic variation was performed using the TaqMan assay. RESULTS: A total of 91 participants who fulfilled our criteria enrolled in this study. Most of the participants were female, with mean age 54.40±7.75 years old, mean HbA1c level of 8.35±1.31%, and the lipid profile indicated normal conditions. There was a significant difference in age (p<0.01), HbA1c level (p=0.04), sex (p<0.01), and smoking status (p<0.01) between low-risk and high-risk groups. The GT genotype of rs9803799 had 187.86 times higher possibility for high-risk of 10-year ASCVD risk than TT genotype (OR=187.86, 95%CI:2.98–11863.51). The dominant model of rs9803799 showed that GT+GG had 94.33 times higher possibility for high-risk of 10-year ASCVD risk than TT genotype (OR=94.33; 95%CI:2.32–3841.21). Other results showed that G allele of rs980377 had 20.48 times higher possibility for high-risk of 10-year ASCVD risk than T allele (OR = 20.48; 95%CI:1.48–283.30). These associations were found after multivariate analysis. CONCLUSION: Our findings indicated that rs9803799 as one of PRKAA2 genetic variations might impact the 10-year ASCVD risk among newly diagnosed T2DM patients receiving monotherapy metformin. After considering non-genetic factors, patient assessment should include potential genetic factors in cases with hyperglycemia involving treatment affecting glucose and lipid metabolism such as monotherapy metformin.   Keywords: PRKAA2, genetic variation, atherosclerosis cardiovascular disease, type 2 diabetes mellitus, metformin, Indonesia