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

Qin, Hao; Ding, Xiang; Gao, Langli; Yang, Ming; Dong, Birong

doi:10.1007/s11357-015-9869-7

Cited by 24 publications

(11 citation statements)

References 34 publications

(55 reference statements)

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“…In vitro studies reported that the rs1207568 is associated with a higher promoter activity [54] upregulating its expression. Hao et al hypothesised that this variant could enhance the levels or activity of Klotho [55]. The KL-VS variant, instead, induces an increase of the catalytic activity of Klotho.…”

Section: Discussionmentioning

confidence: 99%

Klotho and vitamin D in multiple sclerosis: an Italian study

Scazzone¹,

Agnello²,

Sasso³

et al. 2020

aoms

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Introduction: Low vitamin D levels have been recognised as an important risk factor for autoimmune diseases, including multiple sclerosis (MS). MS is a multifactorial disease, the pathogenesis of which contributes both to genetic and environmental factors. Polymorphisms in genes codifying molecules involved in vitamin D homeostasis have been associated with hypovitaminosis D. However, the influence of polymorphisms of Klotho, which codify a protein with a pivotal role in vitamin D metabolism, have never been investigated. The aim of this study was to evaluate the association among genetic variants of Klotho, namely rs1207568 and rs9536314, serum 25(OH)D 3 levels, and multiple sclerosis (both risk and disease progression). Material and methods: 107 patients with MS and 133 healthy controls were enrolled in this study. Serum 25(OH)D 3 levels and genotyping of Klotho SNPs were evaluated in all participants by high-performance liquid chromatography and real-time polymerase chain reaction, respectively. Results: Allelic and genotypic frequencies did not differ between patients and controls. Concerning rs1207568, we found a trend toward lower serum 25(OH)D 3 levels in MS patients with A allele (mutant), both in heterozygosis (AG) and in homozygosis (AA), in comparison to MS patients with G allele in homozygosis (GG) (AG + AA 20.5 ±6.3 μg/l; GG 22.5 ±7.5 μg/l, p = 0.07). Conclusions: Our findings did not identify a role of Klotho in the genetic susceptibility to MS.

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Section: Discussionmentioning

confidence: 99%

Klotho and vitamin D in multiple sclerosis: an Italian study

Scazzone¹,

Agnello²,

Sasso³

et al. 2020

aoms

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“…Humans under age 60 show no cognitive effect of the polymorphism but those over 60 had a slight but significantly higher IQ and better MMSE score [ 43 ]. When humans 90+ years of age were examined, those with the G395A polymorphism were less cognitively impaired and also had higher MMSE scores [ 44 ]. Thus, KL transcriptional changes could impact brain function.…”

Section: Humans Klotho and Cognitive Functionmentioning

confidence: 99%

Klotho, the Key to Healthy Brain Aging?

Laszczyk

King

2018

BPL

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Brain expression of klotho was first described with the initial discovery of the klotho gene. The prominent age-regulating effects of klotho are attributed to regulation of ion homeostasis through klotho function in the kidney. However, recent advances identified brain functions and cell populations, including adult hippocampal neural progenitors, which require klotho. As well, both human correlational studies and mouse models of disease show that klotho is protective against multiple neurological and psychological disorders. This review focuses on current knowledge as to how the klotho protein effects the brain.

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“…In addition to the KL -VS haplotype, there are reports of associations between variants in the KL promoter region and cognition. Mengel-From et al (14) reported that carriers of the rs398655 C allele had better cognitive function than non-carriers and Hao et al (18) reported that those with who are homozygous for the G (guanine) allele at G-395A (rs1207568) have an increased risk of cognitive impairment.…”

Section: Introductionmentioning

confidence: 99%

Variation at the Klotho gene locus does not affect cognitive function in up to 335,074 British Caucasians in the UK Biobank

Amin

Drenos

Blakemore

2019

Preprint

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25The proportion of older adults in Western populations is increasing and there is, 26 therefore, a need to define factors affecting maintenance of physical and 27 cognitive health in old age. Variations in the Klotho (KL) gene, and specifically 28 the KL-VS haplotype, have been identified by several authors as potentially 29 influencing cognitive function and decline. We have attempted to verify the 30 reported associations between KL variants, including the KL-VS haplotype, and 31 cognitive function in up to 335,074 British Caucasian participants aged 40-79 32 years from the UK Biobank. We do not find evidence that KL-VS affects 33 cognitive function or its decline with increasing age. We examined a further 244 34 KL variants and found that rs117650866 was associated with Prospective 35Memory, but could not replicate this in follow-up samples. In conclusion, there is 36 insufficient evidence in the UK Biobank to support the concept that KL variants 37 affect cognitive function or its rate of decline. 38 39 42proportion of older adults. There is, thus, a need to define the factors affecting 43 maintenance of physical and cognitive health in old age. Cognition can be 44 defined as any process that is required for an individual to be aware of their 45 situation and to use that information to respond to it (1). As individuals get older, 46 memory, learning and processing speed decline (2); often leading to reduced 47 independence and increased reliance on families and social care. As life 48 expectancy increases, it becomes ever more necessary to explore some of the 49 factors that might explain variation in cognitive function and cognitive decline in 50 adults. 51 52 Several authors have highlighted variants in the Klotho (KL) gene as associated 53 with ageing. KL is located on chromosome 13 in humans, and encodes a single-54 pass transmembrane protein that acts as an FGF23 co-receptor (3-5). It was 55 first identified in mice by Kuro-o et al. (6) who showed that decreased kl 56 expression resulted in a condition resembling premature ageing. In humans, KL 57 variants have been reported to be associated with longevity, cardiovascular risk 58 factors and cancer (7-10).59 60 In addition, multiple studies have been carried out exploring the relationship 61 between KL variants and cognitive function and decline, mostly focusing on the 62 KL-VS haplotype, which refers to a pair of functional variants that result in 63 F352V (rs9536314) and C370S (rs9527025) substitutions. Previous evidence 64 has been varied: some authors have suggested that among adults aged 70 65 years or more, people homozygous for V (valine) at position 352 have poorer 66 cognitive function (11,12), but also suggests that V352 heterozygotes have 67 better cognitive function than those who are homozygous for (F) phenylalanine 68 at position 352 (11,13). On the other hand, Mengel-From et al. (14) showed 69 that, in Danish populations aged between 92-100 years, V352 heterozygotes 70 had poorer cognition and Almeida et al. (15) showed that among m...

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

Cited by 24 publications

References 34 publications

Klotho and vitamin D in multiple sclerosis: an Italian study

Klotho and vitamin D in multiple sclerosis: an Italian study

Klotho, the Key to Healthy Brain Aging?

Variation at the Klotho gene locus does not affect cognitive function in up to 335,074 British Caucasians in the UK Biobank

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