Investigation of Klotho G395A and C1818T Polymorphisms and Their Association with Serum Glucose Level and Risk of Type 2 Diabetes Mellitus

Aziz, Muhammad Sadiq; Aamir, Aziz-ul-Hasan; Khan, Abad; Khan, Zahid; Shah, Syed Qaiser; Safi, Sher Zaman; Batumalaie, Kalaivani; Alobaid, Hussah M.; Ali, Abid; Imran, Muhammad

doi:10.3390/genes13091532

Cited by 8 publications

(3 citation statements)

References 20 publications

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“…One prospective study of participants with primary hyperoxaluria type 1 found that those with KS had lower levels of Klotho than individuals without nephrocalcinosis and CaOx KS [ 27 ]. Klotho gene G395A single-nucleotide polymorphisms were linked to the formation of renal stones among North Indian patients with KS [ 28 ]. Moreover, a meta-analysis involving five distinct research studies revealed that Klotho prevented the development of urinary stones [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Association between Serum Klotho and Kidney Stones in US Middle-Aged and Older Individuals with Diabetes Mellitus: Results from 2007 to 2016 National Health and Nutrition Survey

Xiao¹,

Xiao²

2023

Am J Nephrol

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Introduction: Kidney stones (KSs) are associated with hematuria and renal failure and pose a significant clinical and public health concern. Diabetes is associated with a higher risk of KSs. In addition, α-Klotho (Klotho), as a novel antiaging protein, is associated with kidney disease, diabetes, and complications and may participate in the pathological mechanism of KSs. However, studies that used large population-based database research are limited. Therefore, this study aimed to investigate whether or not KS prevalence is associated with serum Klotho levels in diabetic adults in the USA. Methods: This nationally representative cross-sectional study used data on diabetic adults in the USA aged 40–79 years from the National Health and Nutrition Examination Survey 2007–2016 cycles. Multivariate logistic regression models were used to calculate the association between Klotho and KS. Restricted cubic splines were used to further test for linearity and explore the shape of the dose-response association. Moreover, we performed stratified and interaction analyses to see if the relationship was stable in different subgroups. Results: Among the 3,537 diabetic patients included in this study (mean age of 61.4 years, consisting of 51.3% males), 543 participants (15.4%) suffered from KS. In the fully adjusted model, Klotho was negatively associated with KS (OR = 0.72; 95% CI: 0.54–0.96; p = 0.027). A negative relationship was observed between the occurrence of KS and Klotho (nonlinear: p = 0.560). Some differences in the association between Klotho and KS were found in stratified analyses; however, these differences lacked statistical significance. Conclusions: Serum Klotho was negatively associated with the incidence of KS; when ln-transformed Klotho concentration increased by 1 unit, the risk of KS was 28% lower.

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Section: Discussionmentioning

confidence: 99%

Association between Serum Klotho and Kidney Stones in US Middle-Aged and Older Individuals with Diabetes Mellitus: Results from 2007 to 2016 National Health and Nutrition Survey

Xiao¹,

Xiao²

2023

Am J Nephrol

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“…In such diabetic and high oxidative stress conditions, studies have shown that pro-diabetic, pro inflammatory and pro-oxidative stress genes are highly expressed. Several studies have reported altered gene expressions in such conditions ( Shaik et al, 2010 ; Safi et al, 2018 ; Bima et al, 2022a ; Aziz et al, 2022 ; Bima et al, 2022b ). In a recent study, Hall et al reported a significant impact of high glucose exposure on global gene expression and DNA methylation in human pancreatic islets ( Hall et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Hyperglycemia-induced oxidative stress and epigenetic regulation of ET-1 gene in endothelial cells

et al. 2023

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Introduction: Hyperglycemia-induced endothelial dysfunction and the subsequent increase of oxidative stress could lead to aberrant regulation of various genes which are responsible for a range of functions. This study aims to find out how hyperglycemia affect oxidative stress and then the expression and methylation of endothelin 1 (ET-1) gene in in human umbilical vein endothelial cells (HUVEC).Methods: Cells were cultured in growth medium and exposed to low and high glucose concentrations to mimic normal and diabetic condition respectively. Computational analysis were performed using UCSC genome browser and eukaryotic promoter database (EPD). The expression of ET-1 gene was investigated by real time PCR. Cytotoxicity and oxidative stress were determined by MTT and DCFH-DA assays respectively. Promoter methylation was assessed by the bisulfite sequencing method.Results: DCFH-DA assay showed that hyperglycemia can significantly increase the regulation of reactive oxygen species synthesis. The relative expression of ET-1 gene was increased due to exposure to high glucose concentration. MTT assay revealed reduced viability of cells due to the glucose induced damage. Methylation analysis revealed hypomethylation of the promoter of ET-1 however the difference was not significant. Out of 175 CpGs at 25 CpG sites, only 36 CpGs were methylated (20.5% methylation) in cell treated with normal glucose. Upon exposure to high glucose only 30 CpGs were methylated in 175 CpGs at 25 CpG sites (17.1% methylation).Discussion: Our study concludes a significantly high expression of ET-1 gene in response to high glucose exposure in HUVECs. It also reports that hyperglycemic condition leads to elevated oxidative stress. No significant change was found in methylation when cells were treated with high and low glucose concentrations.

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“…It has been shown to act as a co-receptor for FGF 23, which helps to regulate calcium and phosphorus metabolism 7 . Studies have shown that α-Klotho inhibits insulin signaling 9 , regulates glucose and fat metabolism 10 and plays a role in the central regulation of energy balance 11 . Recent studies have shown that diabetic patients have reduced serum Klotho levels 12 – 14 .…”

Section: Introductionmentioning

confidence: 99%

Serum α-Klotho and fibroblast growth factor 23 levels are not associated with non-proliferative diabetic retinopathy in type 1 diabetes mellitus

Oner,

Dogan,

Tuzun

et al. 2024

Sci Rep

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Diabetic retinopathy is a commonly observed cause of blindness and is a common problem in individuals with diabetes. Recent investigations have showed the capability of serum α-Klotho and FGF 23 in mitigating the effects of diabetic retinopathy. This study aimed to discover the correlation between FGF 23, α-Klotho, and diabetic retinopathy in type 1 diabetics. This case–control study included 63 diabetic patients and 66 healthy controls. Following an overnight duration of fasting, morning blood samples were taken from both the patient and the control groups. The serum concentrations of α-Klotho and FGF 23 were quantified. An experienced ophthalmologist inspected the retinopathy. All participants in this study have moderate non-proliferative retinopathy. A p value under 0.05 was considered statistically significant. The mean α-Klotho level for retinopathic diabetic patients was 501.7 ± 172.2 pg/mL and 579.6 ± 312.1 pg/mL for non-retinopathic diabetic patients. In comparison, α-Klotho level of the control group was 523.2 ± 265.4 pg/mL (p = 0.531). The mean of FGF 23 level did not demonstrate a significant difference (p = 0.259). The mean FGF 23 level were 75.7 ± 14.0 pg/mL, 74.0 ± 14.8 pg/mL and 79.3 ± 14.4 pg/mL in groups, respectively. In conclusion, there was no significant difference in FGF 23 and α-Klotho levels between type 1 diabetics with and without retinopathy when compared to the control group.

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Investigation of Klotho G395A and C1818T Polymorphisms and Their Association with Serum Glucose Level and Risk of Type 2 Diabetes Mellitus

Cited by 8 publications

References 20 publications

Association between Serum Klotho and Kidney Stones in US Middle-Aged and Older Individuals with Diabetes Mellitus: Results from 2007 to 2016 National Health and Nutrition Survey

Association between Serum Klotho and Kidney Stones in US Middle-Aged and Older Individuals with Diabetes Mellitus: Results from 2007 to 2016 National Health and Nutrition Survey

Hyperglycemia-induced oxidative stress and epigenetic regulation of ET-1 gene in endothelial cells

Serum α-Klotho and fibroblast growth factor 23 levels are not associated with non-proliferative diabetic retinopathy in type 1 diabetes mellitus

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