Genetic association of hypoxia inducible factor 1-alpha (HIF1A) Pro582Ser polymorphism with risk of diabetes and diabetic complications

Ren, Huan; Gao, Yongchao; Chen, Man‐Yun; Chen, Xiaoping; Zhou, Hong‐Hao; Jiang, Ying; Zhang, Wei

doi:10.18632/aging.103213

Cited by 7 publications

(7 citation statements)

References 43 publications

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“…This subgroup analysis results goes in favor of Ekberg et al [ 65 ], and Bi et al [ 66 ] for diabetic complications and Yu et al [ 17 ] and Wei et al [ 37 ] for COPD. The association of diabetic complication risk was also supported by a previous meta-analysis report [ 75 ]. Also the subgroup analysis results of HIF1A 1772 C/T polymorphism showed insignificant association with autoimmune diseases, inflammatory diseases, and preeclampsia under all five genetic models which goes in favor of Wipff et al [ 31 ] and Feng et al [ 25 ] for autoimmune disease, Torres et al [ 27 ], Chachami et al [ 32 ] and Senhaji et al [ 41 ] for inflammatory disease, and Nava-Salazar et al [ 34 ] for preeclampsia.…”

Section: Discussionsupporting

confidence: 71%

“…Also, the HIF1A 1790 G/A polymorphism showed significantly decreasing the risk of other (LDD, HAPC, Pressure injury) disease group under four genetic models (A vs. G, AA vs. GG, AA + GA vs. GG, AA vs. GA + GG) and insignificant association with inflammatory disease, COPD, autoimmune disease and preeclampsia under all genetic models. The association of diabetic complications contradicted the reports by Ren et al [75]. The insignificant result of HIF1A 1790 G/A were supported by Bahadori et al…”

Section: Plos Onementioning

confidence: 80%

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Association of hypoxia inducible factor 1-Alpha gene polymorphisms with multiple disease risks: A comprehensive meta-analysis

et al. 2022

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HIF1A gene polymorphisms have been confirmed the association with cancer risk through the statistical meta-analysis based on single genetic association (SGA) studies. A good number SGA studies also investigated the association of HIF1A gene with several other diseases, but no researcher yet performed statistical meta-analysis to confirm this association more accurately. Therefore, in this paper, we performed a statistical meta-analysis to draw a consensus decision about the association of HIF1A gene polymorphisms with several diseases except cancers giving the weight on large sample size. This meta-analysis was performed based on 41 SGA study’s findings, where the polymorphisms rs11549465 (1772 C/T) and rs11549467 (1790 G/A) of HIF1A gene were analyzed based on 11544 and 7426 cases and 11494 and 7063 control samples, respectively. Our results showed that the 1772 C/T polymorphism is not significantly associated with overall disease risks. The 1790 G/A polymorphism was significantly associated with overall diseases under recessive model (AA vs. AG + GG), which indicates that the A allele is responsible for overall diseases though it is recessive. The subgroup analysis based on ethnicity showed the significant association of 1772 C/T polymorphism with overall disease for Caucasian population under the all genetic models, which indicates that the C allele controls overall diseases. The ethnicity subgroup showed the significant association of 1790 G/A polymorphism with overall disease for Asian population under the recessive model (AA vs. AG + GG), which indicates that the A allele is responsible for overall diseases. The subgroup analysis based on disease types showed that 1772 C/T is significantly associated with chronic obstructive pulmonary disease (COPD) under two genetic models (C vs. T and CC vs. CT + TT), skin disease under two genetic models (CC vs. TT and CC + CT vs. TT), and diabetic complications under three genetic models (C vs. T, CT vs. TT and CC + CT vs. TT), where C allele is high risk factor for skin disease and diabetic complications (since, ORs > 1), but low risk factor for COPD (since, ORs < 1). Also the 1790 G/A variant significantly associated with the subgroup of cardiovascular disease (CVD) under homozygote model, diabetic complications under allelic and homozygote models, and other disease under four genetic models, where the A is high risk factor for diabetic complications and low risk factor for CVD. Thus, this study provided more evidence that the HIF1A gene is significantly associated with COPD, CVD, skin disease and diabetic complications. These might be the severe comorbidities and risk factors for multiple cancers due to the effect of HIF1A gene and need further investigations accumulating large number of studies.

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Section: Discussionsupporting

confidence: 71%

Section: Plos Onementioning

confidence: 80%

Association of hypoxia inducible factor 1-Alpha gene polymorphisms with multiple disease risks: A comprehensive meta-analysis

et al. 2022

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“…Hypoxia plays a vital role in diabetic complications and occurs in tissues central to the development of diabetes (pancreatic β-cells and adipose tissue) and in tissues susceptible to diabetic complications (nerves, retina, heart, blood vessels, kidneys, and wounds) ( 149 ). Hypoxia-inducible factor 1α (HIF-1α) gene polymorphisms may be associated with diabetes and diabetic complications ( 150 ). HIF-1α is a transcription factor that is expressed in response to decreased cellular oxygen partial pressure and activated to participate in angiogenesis, glycolysis, and regulation of vascular tone ( 151 ) The cellular adaptive response to hypoxia is mediated by hypoxia-inducible factor-1α, and hyperglycemia leads to decreased stability and low transcriptional potency of the HIF-1α protein in response to hypoxia ( 152 ), which also leads to a pseudo-hypoxic state that activates HIF-1α activity to adapt to hypoxia ( 153 ).…”

Section: Parallelism Between Dn and Dr Developmentmentioning

confidence: 99%

Parallelism and non-parallelism in diabetic nephropathy and diabetic retinopathy

Tang,

An,

Sun

et al. 2024

Front. Endocrinol.

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Diabetic nephropathy (DN) and diabetic retinopathy (DR), as microvascular complications of diabetes mellitus, are currently the leading causes of end-stage renal disease (ESRD) and blindness, respectively, in the adult working population, and they are major public health problems with social and economic burdens. The parallelism between the two in the process of occurrence and development manifests in the high overlap of disease-causing risk factors and pathogenesis, high rates of comorbidity, mutually predictive effects, and partial concordance in the clinical use of medications. However, since the two organs, the eye and the kidney, have their unique internal environment and physiological processes, each with specific influencing molecules, and the target organs have non-parallelism due to different pathological changes and responses to various influencing factors, this article provides an overview of the parallelism and non-parallelism between DN and DR to further recognize the commonalities and differences between the two diseases and provide references for early diagnosis, clinical guidance on the use of medication, and the development of new drugs.

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“…Accumulating evidence suggests that hypoxia is an important pathogenic factor for diabetes or insulin resistance [71][72][73]. Sestrin2 is important to maintain insulin sensitivity and glucose metabolism through HIF-1α or AMPKdependent autophagic activation [72,74].…”

Section: Sestrin2 and Other Hypoxia-related Diseasesmentioning

confidence: 99%

Sestrin2 in hypoxia and hypoxia-related diseases

et al. 2021

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Objectives: Sestrin2 is a stress-inducible protein and play an important role in adapting stress states of cells. This article reviewed the role of Sestrin2 in hypoxia and hypoxia-related diseases to provide new perspectives for future research and new therapeutic targets for hypoxia-related diseases. Methods: A review was conducted through an electronic search of PubMed and Medline databases. Keywords included Sestrin2, ROS, hypoxia, and hypoxia-related disease. Articles from 2008 to 2021 were mostly included and older ones were not excluded. Results: Sestrin2 is upregulated under various stress conditions, especially hypoxia. Under hypoxic condition, Sestrin2 plays a protective role by reducing the generation of ROS through various pathways, such as adenosine monophosphatea-ctivated protein kinase (AMPK) / mammalian target of rapamycin (mTOR) pathway and nuclear factor-E2-related factor2 (Nrf2) pathway. In addition, Sestrin2 is involved in various hypoxia-related diseases, such as cerebral hypoxic disease, myocardial hypoxic disease, hypoxia-related respiratory disease, and diabetes. Discussion: Sestrin2 is involved in various hypoxia-related diseases and maybe a therapeutic target. Furthermore, most studies focus on cerebral and myocardial ischemia reperfusion. More researches on hypoxia-related respiratory diseases, kidney injury, and diabetes are needed in future.

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Genetic association of hypoxia inducible factor 1-alpha (HIF1A) Pro582Ser polymorphism with risk of diabetes and diabetic complications

Cited by 7 publications

References 43 publications

Association of hypoxia inducible factor 1-Alpha gene polymorphisms with multiple disease risks: A comprehensive meta-analysis

Association of hypoxia inducible factor 1-Alpha gene polymorphisms with multiple disease risks: A comprehensive meta-analysis

Parallelism and non-parallelism in diabetic nephropathy and diabetic retinopathy

Sestrin2 in hypoxia and hypoxia-related diseases

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