Association study of AMP-activated protein kinase subunit genes in polycystic ovary syndrome

Sproul, K.; Jones, Michelle R.; Azziz, Ricardo; Goodarzi, Mark O.

doi:10.1530/eje-09-0245

Cited by 3 publications

(4 citation statements)

References 16 publications

(20 reference statements)

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“…2, A--D). Stimulatory conditions have been well documented to promote allosteric associations between these subunits (65)(66)(67), and this work indicates that the inherent function of the natural UBA domain may be to regulate SNF1 kinase activation by restraining ␣-␥ associations. The mechanism underlying this modulation of association remains to be determined, yet a glucose-responsive association of a peripheral protein(s) with the hydrophobic face of the UBA domain may introduce steric hindrance between the ␣-␥ subunits, thereby preventing full activation.…”

Section: Discussionmentioning

confidence: 80%

The SNF1 Kinase Ubiquitin-associated Domain Restrains Its Activation, Activity, and the Yeast Life Span

Jiao¹,

Postnikoff²,

Harkness³

et al. 2015

Journal of Biological Chemistry

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Background:The UBA domain in the AMP kinase family is poorly defined. Results: This motif restrains kinase activity, resulting in decreased life span and oxidative stress resistance. Conclusion: This inhibitory domain has defined influences with FOXOs on stress and aging. Significance: The overactive kinase created by UBA mutations has positive stress resistance and aging influences that may translate to human metabolic benefits.

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Section: Discussionmentioning

confidence: 80%

The SNF1 Kinase Ubiquitin-associated Domain Restrains Its Activation, Activity, and the Yeast Life Span

Jiao¹,

Postnikoff²,

Harkness³

et al. 2015

Journal of Biological Chemistry

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“…However, variants in PRKAA2 genes were not associated with polycystic ovary syndrome. 24 Campa et al 26 found no statistically significant correlation between breast cancer risk and SNPs in PRKAA2 genes in the European Prospective Investigation on Cancer.…”

Section: Discussionmentioning

confidence: 98%

“…The current literature on PRKAA2 and diseases mainly includes diabetes-related studies. 22,23 Other studies on AMPK polymorphisms have mainly focused on cancer and polycystic ovary syndrome, [24][25][26] and no studies related to PHN have been reported. Thus, the purpose of this study was to investigate the relationship between PRKAA2 and PHN in the southwestern Chinese Han population.…”

Section: Introductionmentioning

confidence: 99%

Effect of AMPK Subunit Alpha 2 Polymorphisms on Postherpetic Pain Susceptibility in Southwestern Han Chinese

Mei¹,

Mu²,

Wang³

et al. 2022

JPR

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Introduction Adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) can influence energy metabolism. Energy metabolism imbalance is closely associated with the occurrence of neuropathic pain (NeP). Rs10789038 and rs2796498 are genetic polymorphisms of PRKAA2 , the gene encoding AMPK, which is closely related to energy metabolism imbalance. This study aimed to explore the relationship between PRKAA2 and postherpetic neuralgia (PHN) in the southwestern Chinese Han population. Methods This study enrolled 132 PHN patients and 118 healthy subjects. The rs10789038 and rs2796498 PRKAA2 genotypes were identified in all participants. The association between these single nucleotide polymorphisms and PHN susceptibility was evaluated in the dominant and recessive models. Haplotype analysis of patients with PHN and healthy controls was performed. Results The PHN patients were older than the healthy subjects ( P < 0.05); however, the other clinical characteristics between two groups were not significantly different (all P >0.05). Genotypes and allele frequencies differed significantly between PHN patients and healthy subjects in the rs10789038 polymorphism ( P < 0.05), but not in rs2796498 ( P > 0.05). In addition, the GG haplotype of rs10789038-rs2796498 correlated negatively with PHN occurrence in haplotype analysis ( P < 0.05). Conclusion PHN occurrence may be related to the PRKAA2 rs10789038 A>G genetic polymorphism in the southwestern Chinese Han population.

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“…Type II diabetes incidence was also associated with variation in PRKAG2 (32). Finally, carrying one or both minor alleles of rs692243 in PRKAG3 was nominally associated with increased risk of polycystic ovary syndrome, but this association did not stay significant after correction for multiple comparisons (33). To the best of our knowledge, this is the first association study exploring variation in AMPK and NHL risk.…”

Section: Discussionmentioning

confidence: 98%

Association of AMP-Activated Protein Kinase with Risk and Progression of Non–Hodgkin Lymphoma

Hoffman

Demanelis

et al. 2013

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background Metabolic dysregulation has been identified as an “emerging hallmark” of cancer. The heterotrimeric AMP-activated protein kinase (AMPK) complex is a central regulator of the metabolic system and an important component of the mTOR pathway and the p53 axis, making it uniquely positioned to influence carcinogenesis through its canonical functions in the metabolic arena, as well as through more traditional mechanisms such as regulation of apoptosis and angiogenesis. Methods We conducted a population-based genetic association study to examine the impact of mutations in AMPK subunit genes on risk of non-Hodgkin’s lymphoma (NHL). We also analyzed public microarray data to determine the expression of AMPK in NHL cells and to assess the influence of AMPK expression on overall survival in NHL patients. Results We identified an AMPK subunit haplotype which was significantly associated with NHL (OR=5.44, 95%CI: 2.15–13.75) in women with no family history of cancer. Haplotypes in two subunits, PRKAA2 and PRKAG3, were nominally associated with the follicular and diffuse large B cell lymphoma histologic subtypes, respectively, although these associations did not retain statistical significance after correction for multiple comparisons. Further, both of these subunits were differentially expressed (p<0.05) in one or more lymphoma cell type, and higher expression of two versions of the AMPK-β subunit were significantly associated with increased five-year survival among NHL patients (p=0.001 and p=0.021). Conclusion These results provide evidence for AMPK involvement in the pathogenesis and progression of NHL. Impact These findings may lead to a novel area of research into NHL treatment and chemoprevention.

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Association study of AMP-activated protein kinase subunit genes in polycystic ovary syndrome

Cited by 3 publications

References 16 publications

The SNF1 Kinase Ubiquitin-associated Domain Restrains Its Activation, Activity, and the Yeast Life Span

The SNF1 Kinase Ubiquitin-associated Domain Restrains Its Activation, Activity, and the Yeast Life Span

Effect of AMPK Subunit Alpha 2 Polymorphisms on Postherpetic Pain Susceptibility in Southwestern Han Chinese

Association of AMP-Activated Protein Kinase with Risk and Progression of Non–Hodgkin Lymphoma

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