Genotype and plasma concentration of cystatin C in patients with late-onset Alzheimer disease.
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.


METHODS
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.


CONCLUSIONS
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.
Chuo
Liang-Jen
LJ
Department of Psychiatry, Taichung Veterans General Hospital, Taichung, and Department of Neurology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
Sheu
Wayne H H
WH
Pai
Ming-Chyi
MC
Kuo
Yu-Min
YM
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000235:genetics*; D000704:Analysis of Variance; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D055316:Cystatin C; D015891:Cystatins / Q000097:blood* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012016:Reference Values; D018709:Statistics, Nonparametric; D013624:Taiwan
D001057:Apolipoproteins E; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins