Genetic Effects of NDUFAF6 rs6982393 and APOE on Alzheimer's Disease in Chinese Rural Elderly: A Cross-Sectional Population-Based Study

Clin Interv Aging. 2022 Feb 24:17:185-194. doi: 10.2147/CIA.S345784. eCollection 2022.

Abstract

Purpose: To investigate the associations of genotypes of NDUFAF6 rs6982393 and APOE and their combined genotypes with the risk of Alzheimer's disease (AD) and mild cognitive impairment (MCI) in Chinese rural elderly.

Methods: This cross-sectional population-based study included 5096 older adults (age ≥60 years, 57.1% female). Genotypes of NDUFAF6 rs6982393 and APOE were detected using the multiple-polymerase chain reaction amplification. We diagnosed AD following the criteria of Diagnostic and Statistical Manual of Mental Disorders, the fourth edition and diagnosed MCI following the Petersen's criteria MCI. Data were analyzed using the logistic regression model.

Results: The overall prevalence of AD and MCI was 3.57% (95% confidence interval [CI]: 0.040, 0.053) and 22.65% (95% CI: 0.223, 0.247), separately. The TT versus CC/CT genotype of NDUFAF6 rs6982393 was related to a higher risk of AD with the multi-adjusted odds ratio (95% CI) being 1.61 (1.02, 2.54) in the total sample, 3.36 (1.48, 7.60) in those aged 60-69, and 1.24 (0.71, 2.17) in those aged 70 years and above. The interaction between genotype of NDUFAF6 rs6982393 with age groups (60-69 versus ≥70 years) was significant on the risk of AD. The presence of APOE ε4 was not significantly associated with the risk of AD. Carrying both NDUFAF6 TT and APOE ε4 was related to a higher risk of AD with the multi-adjusted odds ratio (95% CI) being 2.69 (1.10, 2.56). In addition, there was no significant association between the above genotypes and MCI.

Conclusion: In Chinese rural elderly, the TT versus CT/CC genotype of NDUFAF6 rs6982393 was associated with an increased likelihood of AD; such an association only existed among young-old adults. Carrying both NDUFAF6 rs6982393-TT and APOE ε4 was related to a higher risk of AD. This finding highlights the importance of considering age and combined genotype in studying the genetic profiles of AD.

Keywords: APOE; NDUFAF6 rs6982393; dementia; population-based study.

MeSH terms

  • Aged
  • Alzheimer Disease* / epidemiology
  • Alzheimer Disease* / genetics
  • Apolipoprotein E4 / genetics
  • China / epidemiology
  • Cognitive Dysfunction* / epidemiology
  • Cognitive Dysfunction* / genetics
  • Cross-Sectional Studies
  • Female
  • Genotype
  • Humans
  • Male
  • Mitochondrial Proteins / genetics

Substances

  • Apolipoprotein E4
  • Mitochondrial Proteins
  • NDUFAF6 protein, human

Grants and funding

This study was supported by grants from the National Key R&D Program of China Ministry of Sciences and Technology (grant no.: 2017YFC1310100), the National Natural Science Foundation of China (grants no.: 81861138008 and 82011530139), the Academic Promotion Program of Shandong First Medical University, China (grant no.: 2019QL020), and the Taishan Scholar Program of Shandong Province, China. The funding body did not participate in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.