A potential regulatory single nucleotide polymorphism in the promoter of the Klotho gene may be associated with essential hypertension in the Chinese Han population

Wang, Hu-Lin; Chen, Nansheng; Wang, Zhang; Zhang, Yihua; Si, Liang-Yi; Li, Xuejun; Yang, Qing; Xiao, Hang

doi:10.1016/j.cca.2009.12.004

Cited by 45 publications

(53 citation statements)

References 23 publications

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“…Moreover, old people with Alzheimer's disease have lower cerebrospinal fluid KLOTHO protein levels than those without (Semba et al 2014). Therefore, Klotho protein may function as a humoral factor (Wang et al 2010). Based on these studies, cognitive function and also found that KLOTHO KL-VS heterozygosity is associated with improved cognition and a larger right dorsolateral prefrontal cortex we hypothesized that the A allele can enhance the levels or activity of Klotho in humans.…”

Section: Discussionmentioning

confidence: 97%

“…The potential involvement of the SNP G-395A in KLOTHO gene function remains speculative. Previous studies reported that G-395A can influence the affinity of binding transcription factors and that the A allele exhibits higher promoter activity in vitro (Kawano et al 2002;Wang et al 2010). Furthermore, G-395A exhibits strong linkage disequilibrium, which may allow it to also act as a surrogate for other nearby functional variants (such as G110C, C1818T, and C2298T) (Zhang et al 2007).…”

Section: Discussionmentioning

confidence: 99%

“…The KLOTHO promoter region G-395A (rs1207568) was genotyped using the TaqMan allelic discrimination assay, as previously described by Wang and colleagues (Wang et al 2010). The following primers and probes (Takara, Dalian, China) were used:…”

Section: Klotho Genotype Analysismentioning

confidence: 99%

“…For example, G-395A (rs1207568) is one SNP of the KLOTHO gene located in the promoter region. GG represents the wild-type genotype, whereas GA+AA represents the mutant (A is the mutant allele) for the G-395A polymorphism (Wang et al 2010). G-395A polymorphism has been reported to be associated with age-related diseases.…”

Section: Introductionmentioning

confidence: 99%

“…G-395A polymorphism has been reported to be associated with age-related diseases. For example, the A allele increased the risk of essential hypertension (Wang et al 2010) and cardioembolic stroke (Kim et al 2006), whereas the G allele increased the risk of osteoarthritis (Tsezou et al 2008;Zhang et al 2007). The associations of the KLOTHO gene allele with bone mineral density (Kawano et al 2002;Yamada et al 2005), coronary artery disease (Imamura et al 2006;Rhee et al 2006), and cognitive impairment (Shimokata et al 2006) remain controversial.…”

Section: Introductionmentioning

confidence: 99%

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G-395A polymorphism in the promoter region of the KLOTHO gene associates with reduced cognitive impairment among the oldest old

Qin

Ding

Gao

et al. 2016

AGE

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This study aimed to examine the possible association between G-395A polymorphism in the promoter region of the KLOTHO gene and cognitive impairment among Chinese nonagenarians and centenarians. This study is a secondary analysis of the Project of Longevity and Aging in Dujiangyan (PLAD) study. Community-dwelling Chinese people aged 90 years or older were included. G-395A (rs1207568) genotyping in the promoter region of the KLOTHO gene was performed using the TaqMan allelic discrimination assay. Cognitive function was assessed with the mini-mental status examination (MMSE). A total of 706 participants (68.0 % female; mean age 93.5 ± 3.6 years) were included. The KLOTHO G-395A polymorphism genotype frequencies for the whole sample were 2.0 % AA, 30.3 % GA, and 67.7 % GG. The GG genotype frequencies for the cognitive impairment and control groups were 70.2 and 62.7 %, respectively. Cognitive impairment prevalence was significantly lower in the GA+AA group than in the GG genotype group (61.4 vs. 69.0 %, p = 0.044). GA+AA genotype subjects had a significantly lower risk of cognitive impairment (odds ratio 0.66; 95 % confidence interval 0.44 to 0.98) than GG genotype individuals after adjusting for age, gender, and other relevant risk factors. KLOTHO G-395A polymorphism associates with reduced cognitive impairment in a sample of Chinese nonagenarians and centenarians.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Klotho Genotype Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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G-395A polymorphism in the promoter region of the KLOTHO gene associates with reduced cognitive impairment among the oldest old

Qin

Ding

Gao

et al. 2016

AGE

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microRNA‐199a counteracts glucocorticoid inhibition of bone marrow mesenchymal stem cell osteogenic differentiation through regulation of Klotho expression in vitro

Tang

Wang

et al. 2020

Cell Biology International

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Osteogenic differentiation (OD) of bone marrow mesenchymal stem cells (BMSCs) is critically important for mitigation of osteoporosis. Glucocorticoids (GCs) are extensively used for treating chronic inflammation, although long‐term exposure to GCs is capable of triggering osteoporosis. microRNAs (miRNAs) have been reported to play a critical role in bone diseases. In the present study, we treated BMSCs with dexamethasone (DEX) during OD to stimulate GC‐mediated osteoporosis. Microarray and quantitative polymerase chain reaction (Q‐PCR) assays demonstrated that miR‐199a was upregulated during OD of BMSCs, while DEX treatment caused a significant reduction in miR‐199a. Alkaline phosphatase (ALP) activity, Alizarin red (AR) staining, and Q‐PCR were applied to assess the role of miRNA‐199a overexpression in DEX‐triggered OD inhibition. miR‐199a was able to rescue OD and ALP activity, which were inhibited by DEX. Additionally, we observed that ALP, BMP2, COL1A1, and Runx2 were increased after transfection of miRNA‐199a mimics. Furthermore, we confirmed that miRNA‐199a facilitates OD of BMSCs through direct inhibition of Klotho protein and messenger RNA expression affecting the downstream fibroblast growth factor receptor 1/extracellular‐signal‐regulated kinase and Janus kinase 1/signal transducer and activator of transcription 1 pathways. This study indicates that miR‐199a plays a critical role in preventing GC‐mediated osteoblast differentiation and may function as a promising miRNA biomarker for osteoporosis.

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Soluble Klotho as Biomarker of Vascular Dysfunction in Chronic Kidney Disease

Kitagawa¹,

Sugiyama²,

Nakamura³

et al. 2015

Biomarkers in Disease: Methods, Discoveries and Applications

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A potential regulatory single nucleotide polymorphism in the promoter of the Klotho gene may be associated with essential hypertension in the Chinese Han population

Cited by 45 publications

References 23 publications

G-395A polymorphism in the promoter region of the KLOTHO gene associates with reduced cognitive impairment among the oldest old

G-395A polymorphism in the promoter region of the KLOTHO gene associates with reduced cognitive impairment among the oldest old

microRNA‐199a counteracts glucocorticoid inhibition of bone marrow mesenchymal stem cell osteogenic differentiation through regulation of Klotho expression in vitro

Soluble Klotho as Biomarker of Vascular Dysfunction in Chronic Kidney Disease

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