A novel polymorphism in protein kinase AMP‐activated catalytic subunit alpha 2 (<i>PRKAA2</i>) is associated with type 2 diabetes in the Han Chinese population

Shen, Jingtao; Ge, Weihong; Fang, Yun; Liu, Huan

doi:10.1111/1753-0407.12449

Cited by 10 publications

(24 citation statements)

References 32 publications

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“…Keshavarz et al found that the PRKAA2 SNP rs1418442 A/G was relevant to T2DM in Japanese individuals and another study implied that PRKAA2 variants were significantly relevant to serum lipoproteins in normal female Caucasians . Recently, Shen et al suggested that the G allele of the PRKAA2 SNP rs2746342 was significantly associated with an increased risk of T2DM in the Chinese Han population . However, in the present study, rs2746342 was not associated with T2DM susceptibility as such.…”

Section: Discussioncontrasting

confidence: 68%

“…However, in the present study, rs2746342 was not associated with T2DM susceptibility as such. This apparent discrepancy may be due to gene–environment or gene–region interactions, because the subjects in the present study were from northern China (Zhengzhou, Henan Province), whereas those in the study of Shen et al were from southern China (Nanjing, Jiangsu Province). In addition, statistical parameters, such as sample size (e.g.…”

Section: Discussioncontrasting

confidence: 64%

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Effect of AMP‐activated protein kinase subunit alpha 2 (PRKAA2) genetic polymorphisms on susceptibility to type 2 diabetes mellitus and diabetic nephropathy in a Chinese population

et al. 2017

Journal of Diabetes

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Background: It is well known that AMP-activated protein kinase (AMPK) is a key factor affecting the development of type 2 diabetes mellitus (T2DM). The single nucleotide polymorphism (SNP) rs2746342 in the AMPK alpha 2 subunit gene (PRKAA2) has been found to be associated with susceptibility to T2DM in the Chinese Han population. The present study further investigates the association of PRKAA2 genotypes with susceptibility to T2DM and its complication, diabetic nephropathy. Methods: The PRKAA2 genotypes of 406 T2DM patients and 214 controls from the Chinese Han population were determined with regard to SNPs rs10789038, rs2796498 and rs2746342. The association between these SNPs and susceptibility to T2DM and diabetic nephropathy was evaluated. The clinical characteristics differed significantly between T2DM patients and controls. Results: After adjustment for age, sex and body mass index, there was an obvious relationship between T2DM and both rs10789038 (odds ratio [OR] 1.634; P = 0.015) and rs2796498 (OR 0.656; P = 0.030), but not rs2746342. There was haplotype association of PRKAA2 rs10789038-rs2796498-rs2746342 with T2DM susceptibility. In addition, rs2796498 was found to be related to the susceptibility to diabetic nephropathy. Conclusions: Polymorphisms in rs10789038 and rs2796498 are associated with the susceptibility to T2DM, and rs2796498 may be related to diabetic nephropathy.

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Section: Discussioncontrasting

confidence: 68%

Section: Discussioncontrasting

confidence: 64%

Effect of AMP‐activated protein kinase subunit alpha 2 (PRKAA2) genetic polymorphisms on susceptibility to type 2 diabetes mellitus and diabetic nephropathy in a Chinese population

et al. 2017

Journal of Diabetes

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“…Furthermore, this study found that the TT genotype of rs2746342 had higher FBG and HbA1c levels signi cantly than GG+GT among study subjects before receiving metformin. Conversely, Shen et al reported that the G allele had a higher FBG level and T2DM risk [22] . It could be caused by dissimilar ethnicity, where Shen et al focused on Han Chinese, and this study focused on Indonesia.…”

Section: Discussionmentioning

confidence: 95%

“…An animal study con rmed that 10 weeks of metformin treatment signi cantly escalated AMPK phosphorylation on the a2 subunit [27]. Several PRKAA2 genetic variations have been investigated to increase T2DM risk, including that's located in the intron region [21,22,28]. Nevertheless, only a few studies observe that SNP is related to metformin responses [23].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of PRKAA2 Genetic Variation on Metformin Efficacy as an Initial Therapy Among Drug-Naïve Patients With Type II Diabetes Mellitus

Virginia¹,

Wahyuningsih²,

Nugrahaningsih³

2020

Preprint

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Background: Metformin is the most popular oral antidiabetic agent, which is recommended as initial monotherapy. AMPK is the pivotal target of metformin molecular mechanisms. AMPK subunit a2 (encoded by PRKAA2) is a gene contributable to increase type 2 diabetes mellitus (T2DM) risk. This study aimed to evaluate PRKAA2 rs2796498, rs2746342, and rs980799 genetic variations on metformin efficacy.Methods: This study enrolled 191 newly diagnosed Indonesia T2DM patients in primary health care. Patients who received metformin as monotherapy for at least 3 months were included for genotyping. Genotyping was performed using the Taqman assay.Results: Baseline characteristics showed that BMI was higher among AA than GG+AG (p=0.04). Patients with TT genotype showed a higher FBG and HbA1c than GG+GT (p=0.02 and p=0.02, respectively). There was no significant difference in allele and genotype frequencies between responders and non-responders group in PRKAA2 rs2796498, rs9803799, and rs2746342. However, among PRKAA2 rs2796498, AG carrier had 0.32 times of responding in metformin efficacy after adjusting BMI, WC, blood pressure, lipid profiles, and eGFR. Dominant model of rs2796498 showed a significant association (OR=0.34, 95%CI=0.13 – 0.90) to metformin efficacy. Conclusions: Our findings suggest that PRKAA2 rs2796498 genetic variation may affect metformin efficacy, especially AG carrier, in drug-naïve T2DM patients.

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“…In contrast to AMPK's well characterized molecular functions in lipid, glucose and energy metabolism, the impact of common genetic variation in its subunit genes on metabolic disorders is less well studied. Single-gene-focused reports described effects of SNPs in PRKAA2, PRKAG2 and PRKAG3 on cholesterol metabolism [4][5][6] and of SNPs in PRKAA1, PRKAA2 and PRKAG2 on type-2 diabetes and type-2 diabetes-related traits (fasting glucose, insulin resistance, diabetic nephropathy, coronary artery disease) in Asian cohorts [6][7][8][9][10][11][12]. On the other hand, studies in Pima Indians and Caucasians on selected AMPK subunit genes (PRKAA2, PRKAB1, PRKAB2, PRKAG2) failed to show significant SNP associations with type-2 diabetes and related traits [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

AMPK Subunits Harbor Largely Nonoverlapping Genetic Determinants for Body Fat Mass, Glucose Metabolism, and Cholesterol Metabolism

Randrianarisoa

Lehn-Stefan

Krier

et al. 2019

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a heterotrimeric enzyme and central regulator of cellular energy metabolism. The impact of single nucleotide polymorphisms (SNPs) in all 7 AMPK subunit genes on adiposity, glucose metabolism, and lipid metabolism has not yet been systematically studied. Objective To analyze the associations of common SNPs in all AMPK genes, and of different scores thereof, with adiposity, insulin sensitivity, insulin secretion, blood glucose, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, total cholesterol, and triglycerides. Study Design and Methods A cohort of 2789 nondiabetic participants from the Tübingen Family study of type 2 diabetes, metabolically characterized by oral glucose tolerance test and genotyped by genome-wide SNP array, was analyzed. Results We identified 6 largely nonoverlapping SNP sets across 4 AMPK genes (PRKAA1, PRKAA2, PRKAG2, PRKAG3) associated with adiposity, insulin sensitivity, insulin secretion, blood glucose, total/LDL cholesterol, or HDL cholesterol, respectively. A genetic score of body-fat-increasing alleles revealed per-allele effect sizes on body mass index (BMI) of +0.22 kg/m2 (P = 2.3 × 10–7), insulin sensitivity of −0.12 × 1019 L2/mol2 (P = 9.9 × 10–6) and 2-hour blood glucose of +0.02 mmol/L (P = 0.0048). Similar effects on blood glucose were observed with scores of insulin-sensitivity-reducing, insulin-secretion-reducing and glucose-raising alleles, respectively. A genetic cholesterol score increased total and LDL cholesterol by 1.17 mg/dL per allele (P = 0.0002 and P = 3.2 × 10–5, respectively), and a genetic HDL score decreased HDL cholesterol by 0.32 mg/dL per allele (P = 9.1 × 10–6). Conclusions We describe largely nonoverlapping genetic determinants in AMPK genes for diabetes-/atherosclerosis-related traits, which reflect the metabolic pathways controlled by the enzyme. Formation of trait-specific genetic scores revealed additivity of allele effects, with body-fat-raising alleles reaching a marked effect size. (J Clin Endocrinol Metab 105: 14–25, 2020)

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A novel polymorphism in protein kinase AMP‐activated catalytic subunit alpha 2 (PRKAA2) is associated with type 2 diabetes in the Han Chinese population

Abstract: The rs2746342 polymorphism is significantly associated with susceptibility to T2DM and seems to interact with the rs2143754 polymorphism in the modulation of FPG in the Han Chinese population.

Cited by 10 publications

References 32 publications

Effect of AMP‐activated protein kinase subunit alpha 2 (PRKAA2) genetic polymorphisms on susceptibility to type 2 diabetes mellitus and diabetic nephropathy in a Chinese population

Effect of AMP‐activated protein kinase subunit alpha 2 (PRKAA2) genetic polymorphisms on susceptibility to type 2 diabetes mellitus and diabetic nephropathy in a Chinese population

Evaluation of PRKAA2 Genetic Variation on Metformin Efficacy as an Initial Therapy Among Drug-Naïve Patients With Type II Diabetes Mellitus

AMPK Subunits Harbor Largely Nonoverlapping Genetic Determinants for Body Fat Mass, Glucose Metabolism, and Cholesterol Metabolism

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