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

PLoS One. 2015 Jul 21;10(7):e0132156. doi: 10.1371/journal.pone.0132156. eCollection 2015.

Abstract

Background: Mild 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.

Methods: DNA 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.

Results: We 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).

Conclusion: Our 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Asian People / ethnology*
  • Asian People / legislation & jurisprudence
  • China / ethnology
  • Cognitive Dysfunction / ethnology
  • Cognitive Dysfunction / genetics*
  • DNA Methylation*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Glucuronidase / genetics*
  • Humans
  • Klotho Proteins
  • Male
  • Promoter Regions, Genetic

Substances

  • Glucuronidase
  • Klotho Proteins

Grants and funding

The research was supported by the grants from the National Natural Science Foundation of China (81471398, 81070873, 31100919 and 81371469), the 973 Program from the Ministry of Science and Technology of China (2013CB835100), the Natural Science Foundation of Zhejiang Province (LR13H020003), the Disciplinary Project of Ningbo University (B01350104900), and the3 K. C. Wong Magna Fund in Ningbo University.