Liang-Jen Chuo1, Wayne H H Sheu, Ming-Chyi Pai, Yu-Min Kuo. 1. Department of Psychiatry, Taichung Veterans General Hospital, Taichung, and Department of Neurology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
Abstract
BACKGROUND: A polymorphism locating at position 73 of cystatin C (CST3) exon 1 was suggested to be associated with Alzheimer disease (AD), but with contradictory results. The relationship between the CST3 genotype and the cystatin C plasma level in AD remains unknown. OBJECTIVE: We aim to determine the association between CST3 polymorphism and the plasma levels of cystatin C in AD and nondemented control individuals. METHOD: The polymorphisms of the CST3 genotype were determined using PCR followed by restriction fragment length polymorphism analysis, and the plasma cystatin C concentrations were quantified by sandwich ELISA in 175 AD and 461 control subjects. RESULTS: Although the CST3A allele frequencies were similar between the two groups, the CST3A/A homozygote was significantly associated with late-onset AD. As expected, the established AD genetic risk factor APOE epsilon4 allele was overrepresented in the AD cohort. The plasma cystatin C levels were lower in the AD patients than in the control group. Furthermore, plasma cystatin C levels were associated positively with age and negatively with CST3A allele in the control group. CONCLUSION: The homozygous CST3A/A genotype confers a risk for AD in Taiwan Chinese. Such an association may be due to the reduced level of cystatin C in the peripheral circulation. Copyright (c) 2007 S. Karger AG, Basel.
BACKGROUND: A polymorphism locating at position 73 of cystatin C (CST3) exon 1 was suggested to be associated with Alzheimer disease (AD), but with contradictory results. The relationship between the CST3 genotype and the cystatin C plasma level in AD remains unknown. OBJECTIVE: We aim to determine the association between CST3 polymorphism and the plasma levels of cystatin C in AD and nondemented control individuals. METHOD: The polymorphisms of the CST3 genotype were determined using PCR followed by restriction fragment length polymorphism analysis, and the plasma cystatin C concentrations were quantified by sandwich ELISA in 175 AD and 461 control subjects. RESULTS: Although the CST3A allele frequencies were similar between the two groups, the CST3A/A homozygote was significantly associated with late-onset AD. As expected, the established AD genetic risk factor APOE epsilon4 allele was overrepresented in the AD cohort. The plasma cystatin C levels were lower in the ADpatients than in the control group. Furthermore, plasma cystatin C levels were associated positively with age and negatively with CST3A allele in the control group. CONCLUSION: The homozygous CST3A/A genotype confers a risk for AD in Taiwan Chinese. Such an association may be due to the reduced level of cystatin C in the peripheral circulation. Copyright (c) 2007 S. Karger AG, Basel.
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