The association of the Klotho polymorphism rs9536314 with parameters of calcium-phosphate metabolism in patients on long-term hemodialysis

Marchelek-Myśliwiec, Małgorzata; Różański, Jacek; Ogrodowczyk, Aldona; Dutkiewicz, Grażyna; Dołęgowska, Barbara; Sałata, Daria; Budkowska, Marta; Safranow, Krzysztof; Stępniewska, Joanna; Wiśniewska, Magda; Ciechanowski, Kazimierz

doi:10.3109/0886022x.2016.1162062

Cited by 8 publications

(5 citation statements)

References 33 publications

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“…Analyses of alleles and genotypes crude frequencies of nine SNPs of genes codifying for key cytokine and receptors involved in kidney damage pathogenesis do not allow to identify associations with the Klotho, in spite of the above-mentioned data on the role of rs577912 polymorphism as risk factors of mortality in dialyzed patients [13] and the role of rs9536314 in the so-called longevity trait [17]. In a study performed in 2016, it was shown that the GG genotype is associated with reduced survival and poor prognosis in dialysis patients compared to the TT and TG genotypes [18] but we were unable to confirm this observation in our population. Similarly, FGF23 rs7955866 and IGF1 rs35767 were not found to be associated with ESRD.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, Klotho polymorphisms involved in metabolic disorders and cardiovascular pathologies might play a role in favoring progression to ESRD. In particular, rs564481 and rs9536314 might play a role, being implied in metabolic diseases and potentially influencing the prognosis of CKD [ 15 , 16 , 17 , 18 ]. In particular, rs56481 might influence hypertension susceptibility and creatinine serum levels in different populations [ 15 , 16 , 17 ] whereas rs9536314 might influence the kidney failure susceptibility impinging on the kidney function decline due to aging.…”

Section: Introductionmentioning

confidence: 99%

“…In particular, rs56481 might influence hypertension susceptibility and creatinine serum levels in different populations [ 15 , 16 , 17 ] whereas rs9536314 might influence the kidney failure susceptibility impinging on the kidney function decline due to aging. Actually, a pathophysiological modification associated with chronic kidney disease mimics that of elderly individuals, which underlies shared clinical characteristics such as an increased risk of infection and atherosclerosis [ 18 , 19 ]. Moreover, rs9536314 was the polymorphism most frequently involved in association studies on cardiovascular and non-cardiovascular mortality.…”

Section: Introductionmentioning

confidence: 99%

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MIF rs755622 and IL6 rs1800795 Are Implied in Genetic Susceptibility to End-Stage Renal Disease (ESRD)

Guarneri

Scola

Giarratana

et al. 2022

Genes

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Chronic kidney disease (CKD) is characterized by an increased risk of kidney failure and end-stage renal disease (ESRD). Aging and comorbidities as cardiovascular diseases, metabolic disorders, infectious diseases, or tumors, might increase the risk of dialysis. In addition, genetic susceptibility factors might modulate kidney damage evolution. We have analyzed, in a group of ESRD patients and matched controls, a set of SNPs of genes (Klotho rs577912, rs564481, rs9536314; FGF23 rs7955866; IGF1 rs35767; TNFA rs1800629; IL6 rs1800795; MIF rs755622, rs1007888) chosen in relation to their possible involvement with renal disease and concomitant pathologies. Analysis of the raw data did indicate that IL6 rs180795 and MIF rs755622 SNPs might be markers of genetic susceptibility to ESRD. In particular, the C positive genotypes of MIF rs755622, (dominant model) seem to be an independent risk factor for ESDR patients (data adjusted for age, gender, and associated pathologies). Stratifying results according to age MIF rs755622 C positive genotype frequencies are increased in both the two age classes considered (<59 and ≥59-year-old subjects). Analyses of data according to gender allowed us to observe that ESRD women shoved a significantly reduced frequency of genotypes bearing IL6 rs180795 C allele. In addition, MIF rs755622 might interact with diabetes or hypercholesterolemia in increasing susceptibility to ESRD. In conclusion, our data indicate that some polymorphisms involved in the regulation of both renal function and inflammatory response can influence the evolution of chronic kidney disease and suggest that the modulation of the activities of these and other genes should also be considered as therapeutic targets on to intervene with innovative therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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MIF rs755622 and IL6 rs1800795 Are Implied in Genetic Susceptibility to End-Stage Renal Disease (ESRD)

Guarneri

Scola

Giarratana

et al. 2022

Genes

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“…Evidence is limited to candidate gene association studies, which have significant issues with reproducibility and publication bias. Studies looked for SNP associations with hemodialysis outcomes including vascular access issues, 56 - 61 biochemical indices, 62 - 65 inflammation, 66 - 68 cardiovascular comorbidities 66 , 69 - 75 and mortality 76 - 79 and PD outcomes including peritoneal transport characteristics, 80 - 84 peritonitis risk, 85 - 87 or risk of encapsulating peritoneal sclerosis 88 ( Supplemental Table 1 ). Sample sizes were inadequate to confidently identify variants of reasonable effect sizes (average sample size of 246, range 67-777 patients).…”

Section: Reviewmentioning

confidence: 99%

Opportunities and Challenges for Genetic Studies of End-Stage Renal Disease in Canada

Kalatharan

Lemaire

Lanktree

2018

Can J Kidney Health Dis

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Purpose of review:Genetic testing can improve diagnostic precision in some patients with end-stage renal disease (ESRD) providing the potential for targeted therapy and improved patient outcomes. We sought to describe the genetic architecture of ESRD and Canadian data sources available for further genetic investigation into ESRD.Sources of information:We performed PubMed searches of English, peer-reviewed articles using keywords “chronic kidney disease,” “ESRD,” “genetics,” “sequencing,” and “administrative databases,” and searched for nephrology-related Mendelian diseases on the Online Mendelian Inheritance in Man database.Methods:In this narrative review, we discuss our evolving understanding of the genetic architecture of kidney disease and ESRD, the risks and benefits of using genetic data to help diagnose and manage patients with ESRD, existing public Canadian biobanks and databases, and a vision for future genetic studies of ESRD in Canada.Key findings:ESRD has a polygenic architecture including rare Mendelian mutations and common small effect genetic polymorphism contributors. Genetic testing will improve diagnostic accuracy and contribute to a precision medicine approach in nephrology. However, the risk and benefits of genetic testing needs to be considered from an individual and societal perspective, and further research is required. Merging existing health data, linking biobanks and administrative databases, and forming Canadian collaborations hold great potential for genetic research into ESRD. Large sample sizes are necessary to perform the suitably powered investigations required to bring this vision to reality.Limitations:This is a narrative review of the literature discussing future directions and opportunities. It reflects the views and academic biases of the authors.Implications:National collaborations will be required to obtain sample sizes required for impactful, robust research. Merging established datasets may be one approach to obtain adequate samples. Patient education and engagement will improve the value of knowledge gained.

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“…-Wnt pathway drives cardiac fibrosis in individuals with CKD. As Zhou et al showed, klotho's full-length and secreted form are hostile to Wnt/β-catenin activity, TA B L E 1(Marchelek-Myśliwiec et al, 2016;Nazarian et al, 2017;Valdivielso et al, 2019) …”

mentioning

confidence: 99%

A study of the molecular mechanism of quercetin and dasatinib combination as senolytic in alleviating age‐related and kidney diseases

Alharbi

Afzal

Altamimi

et al. 2022

Journal of Food Biochemistry

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Aging is a significant risk factor for the majority of prevalent human illnesses. The chance of having severe chronic conditions grows dramatically with advancing age. Indeed, more than 90% of people over 65 get at least one chronic disease, including diabetes, heart disease, malignancy, memory loss, and kidney disease, whereas more than 70% have two or more of these ailments. Mouse and human aging lead to increased senescent cells and decreased klotho concentrations. Mice lacking the protein α‐klotho show faster aging, similar to human aging. α‐Klotho upregulation extends life and slows or suppresses the onset of many age‐related illnesses and kidney diseases. Like the consequences of α‐klotho deficiency, senescent cell accumulation is linked to tissue dysfunction in various organs and multiple age‐related kidney diseases. In addition, α‐klotho and cell senescence are negatively and presumably mechanistically linked. Earlier research has demonstrated that klotho exerts its protective effects in age‐related and kidney disease by interacting with Wnt ligands, serving as an endogenous antagonist of Wnt/β‐catenin signaling. In addition, decreasing senescent cell burden with senolytics, a class of drugs that remove senescent cells selectively and extend the life span of mice. In this work, we are studying the molecular mechanism of the combination of quercetin and dasatinib as senolytic in easing age‐related chronic renal illness by altering the level of klotho/Wnt/β‐catenin. Practical applications There is an inverse relationship between the onset and the development of age‐related disorders and cellular senescence and Klotho. Earlier attempts to suppress transforming growth factor‐beta 1 (TGF‐β1) in kidney disease with anti‐TGF‐β1 antibodies were ineffective, and this should be kept in mind. Senolytic medications may benefit from targeting senescent cells, which enhances the protective factor α‐klotho. In addition, our study provides a unique, translationally feasible route for creating orally active small compounds to enhance α‐klotho, which may also be a valuable biomarker for age‐related kidney disease. Additionally, other aspects of aging can be affected by senolytics, such as limiting age‐related mitochondrial dysfunction, lowering inflammation and fibrosis, blunting reactive oxygen species (ROS) generation, decreasing deoxyribonucleic acid (DNA) damage, and reinforcing insulin sensitivity. Senolytic agents have been shown to increase adipose progenitor and cardiac progenitor cell activity in aging animals and animals with cellular senescence‐related diseases, such as heart, brain, and kidney disease.

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The association of the Klotho polymorphism rs9536314 with parameters of calcium-phosphate metabolism in patients on long-term hemodialysis

Cited by 8 publications

References 33 publications

MIF rs755622 and IL6 rs1800795 Are Implied in Genetic Susceptibility to End-Stage Renal Disease (ESRD)

MIF rs755622 and IL6 rs1800795 Are Implied in Genetic Susceptibility to End-Stage Renal Disease (ESRD)

Opportunities and Challenges for Genetic Studies of End-Stage Renal Disease in Canada

A study of the molecular mechanism of quercetin and dasatinib combination as senolytic in alleviating age‐related and kidney diseases

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