Background:
Approximately 40 independent Single Nucleotide Polymorphisms (SNPs) have
been associated with Alzheimer’s Disease (AD) or cognitive decline in genome-wide association studies.
Methods:
We aimed to evaluate the joint effect of genetic polymorphisms and environmental factors on
the progression from Mild Cognitive Impairment (MCI) to AD (MCI-AD progression) in a Chinese
community cohort.
Conclusion:
Demographic, DNA and incident AD diagnosis data were derived from the follow-up of 316
participants with MCI at baseline of the Shanghai Aging Study. The associations of 40 SNPs and environmental
predictors with MCI-AD progression were assessed using the Kaplan-Meier method with the
log-rank test and Cox regression model.
Results:
Rs4147929 at ATP-binding cassette family A member 7 (ABCA7) (AG/AA vs. GG, hazard ratio
[HR] = 2.43, 95% confidence interval [CI] 1.24-4.76) and body mass index (BMI) (overweight vs.
non-overweight, HR = 0.41, 95% CI 0.22-0.78) were independent predictors of MCI-AD progression. In
the combined analyses, MCI participants with the copresence of non-overweight BMI and the ABCA7
rs4147929 (AG/AA) risk genotype had an approximately 6-fold higher risk of MCI-AD progression
than those with an overweight BMI and a non-risk genotype (HR = 6.77, 95% CI 2.60-17.63). However,
a nonsignificant result was found when participants carried only one of these two risk factors (nonoverweight
BMI and AG/AA of ABCA7 rs4147929).
Conclusion:
ABCA7 rs4147929 and BMI jointly affect MCI-AD progression. MCI participants with the
rs4147929 risk genotype may benefit from maintaining an overweight BMI level with regard to their
risk for incident AD.