KL
Klotho is expressed at the highest levels in the kidney and is involved in calcium and phosphate homeostasis, as well as in aging-related signaling cascades, such as insulin signaling 1. Klotho is present in two isoforms: one attached to the membrane and one circulating in the body. The membrane isoform acts as a coreceptor to a hormone known as FGF23 that regulates phosphate metabolism and vitamin D synthesis in the kidney. The circulating isoform is detected in the blood and cerebrospinal fluid and is found in a wide range of organs, including the brain2. Klotho levels decline with aging and have been linked with longevity 4 and protection against neurodegenerative diseases 5. The KLOTHO-VS allele resulting in increased levels of circulating Klotho was shown to reduce the risk of Alzheimer’s disease associated with defective ApoE alleles 6.
| rsID Number | Major Allele | Minor Allele | Minor Allele Frequency (%) | Major Amino Acid | Minor Amino Acid |
|---|---|---|---|---|---|
| rs9536314 | t | g | 25 | Phe | Val |
Risk Description
This variant is part of the KLOTHO-VS haplotype, resulting in higher levels of circulating KLOTHO. The G allele of this SNP (in at least one copy of the KL gene) has been associated with increased longevity and reduced risk of Alzheimer’s disease, particularly in the careers of the defective ApoE allele (ApoE e4) that predisposes to Alzheimer’s 6.
Discuss this information with your doctor before taking any course of action.
Citations:
- https://www.frontiersin.org/articles/10.3389/fragi.2022.931331/full
- https://www.science.org/doi/10.1126/science.1112766?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
- https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2020.00560/full
- https://academic.oup.com/biomedgerontology/article/66A/7/794/616322?login=false
- https://portlandpress.com/neuronalsignal/article/5/2/NS20200101/228755/Exploiting-the-neuroprotective-effects-of-klotho
- https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2798873
| rsID Number | Major Allele | Minor Allele | Minor Allele Frequency (%) | Major Amino Acid | Minor Amino Acid |
|---|---|---|---|---|---|
| rs9527025 | g | c | 25 | Cys | Ser |
Risk Description
This variant is part of the KLOTHO-VS haplotype, resulting in higher levels of circulating KLOTHO. The C allele of this SNP (in at least one copy of the KL gene) has been associated with increased longevity and reduced risk of Alzheimer’s disease, particularly in the careers of the defective ApoE allele (ApoE e4) that predisposes to Alzheimer’s.
Discuss this information with your doctor before taking any course of action.
Citations:
- https://www.frontiersin.org/articles/10.3389/fragi.2022.931331/full
- https://www.science.org/doi/10.1126/science.1112766?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
- https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2020.00560/full
- https://academic.oup.com/biomedgerontology/article/66A/7/794/616322?login=false
- https://portlandpress.com/neuronalsignal/article/5/2/NS20200101/228755/Exploiting-the-neuroprotective-effects-of-klotho
- https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2798873