Population Difference in the Associations of KLOTH Promoter Methylation with Mild Cognitive Impairment in Xinjiang Uygur and Han Populations

Abstract

BackgroundMild cognitive impairment (MCI) is the intermediate stage of the cognitive changes between normal aging and dementia. KLOTH is an age-related gene that may contribute to the risk of MCI. The aim of our study was to explore the association between KLOTHO promoter methylation and MCI in Xinjiang Uygur and Han populations.MethodsDNA methylation assay was performed using the bisulphite pyrosequencing technology among 96 Uygur (48 MCI and 48 controls) and 96 Han (48 MCI and 48 controls) Chinese individuals from Xinjiang province of China.ResultsWe found significant association between KLOTHO promoter methylation and MCI in the Han Chinese (CpG1: p = 3.77E-06; CpG2: p = 1.91E-07; CpG3: p = 5.83E-07; CpG4: p = 2.23E-05; CpG5: p = 3.03E-06) but not in the Uygur Chinese. Higher KLOTHO promoter methylation levels were found in Han MCI patients than Uygur MCI patients for all the five CpGs (adjusted p values by age < 0.02).ConclusionOur results showed that KLOTHO promoter hypermethylation contributed to the MCI risk in Xinjiang Han Chinese but not in Xinjiang Uygur Chinese. The population difference of KLOTHO methylation in the risk of MCI required further investigation in the future.

Rhein reverses Klotho repression via promoter demethylation and protects against kidney and bone injuries in mice with chronic kidney disease

“…45 Epigenetic modification, especially the DNA methylation, is emerging as a critical contributor to both acute and CKD progression. 18,48 Klotho promoter is characterized by typical CpG islands, and its differential methylation is associated with aging-related disorders 20 and various cancer conditions. 21,47 Elevated Klotho promoter methylation has been linked to the severity of CKD in patients and in uremic toxin-induced CKD in experimental animals.…”

“…18 Population-based genomewide quantitative evaluations of DNA methylation demonstrate that DNA hypermethylation and DNA hypomethylation occur at different loci in CKD. 18 Aberrant Klotho promoter methylation has been reported in aging-related disorders 19,20 and various cancers. 21,22 Recent studies further suggest that Klotho promoter hypermethylation is associated with the pathogenesis of acute kidney disease and CKD.…”

DNA methylation analyses of the candidate genes identified by a methylome‐wide association study revealed common epigenetic alterations in schizophrenia and bipolar disorder

“…CTAGE11P is a pseudogene and its function is unknown. Ethnic differences of DNA methylation in some genes have been reported, and DNA methylation of the two CpG sites in CTAGE11P might be affected in a similar manner.…”

“…CTAGE11P is a pseudogene and its function is unknown. Ethnic differences of DNA methylation in some genes have been reported, [30][31][32] and DNA methylation of the Table 1). CT, control.…”

Significant association of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) rs3846662 and sirtuin 1 (SIRT1) rs7895833 and apolipoprotein E (APOE) hypermethylation with mild cognitive impairment (MCI)

“…Our previous studies have found that the promoter methylation of Klotho ( KL ) is ethnically different among Chinese Uygur and Han populations in Xinjiang. [25,26]…”