rs9536314

rs9536314, also known as c.1062T>G, p.Phe352Val and F352V, represents a variant in the KL (Klotho) gene on chromosome 13. Together with rs9527025 (C370S), which it co-segregates with, a haplotype ("KL-VS") has been described that is reported to increase klotho secretion and may alter its functions; the alternative haplotype is named KL-FC (due to the F from F352V and C from C370S). The klotho protein is a hormone found primarily in the kidney and choroid plexus of the brain. At the genetic level, the Klotho gene is reported to affect longevity in mice and perhaps humans , and KL-VS heterozygosity (but not homozygosity) has been associated with greater brain cortical volume . At the protein level, older adults with higher plasma klotho concentrations tend to show lower less decline with age on standardized cognitive tests , adults with higher stress tend to have lower plasma klotho levels , and transgenic mice bred to have excess human amyloid precursor protein (to simulate Alzheimer's disease) score better on some tests when their klotho levels are increased . Most of the studies cited above for studies of klotho in humans should be considered preliminary for at least two reasons: they are not based on large sample sizes, and, they haven't been replicated by independent investigators. In addition, there is a report showing no difference in the klotho plasma levels between FC/FC and FC/VS individuals , as well as a report showing KL-VS heterozygotes had poorer cognitive function than noncarriers , in contrast to the studies cited above. Variation in longevity gene KLOTHO is associated with greater cortical volumes

G;G

See discussion at rs9536314

G;T

See discussion at rs9536314