Polymorphisms in the PON gene cluster are associated with Alzheimer disease

被引:82
作者
Erlich, PM
Lunetta, KL
Cupples, LA
Huyck, M
Green, RC
Baldwin, CT
Farrer, LA
机构
[1] Boston Univ, Sch Med, Genet Program, Dept Med, Boston, MA 02118 USA
[2] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA
[3] Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA
[4] Boston Univ, Sch Med, Ctr Human Genet, Boston, MA 02118 USA
[5] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA
[6] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA
关键词
D O I
10.1093/hmg/ddi428
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Paraoxonase is an arylesterase enzyme that is expressed in the liver and found in the circulation in association with apoA1 and the high-density lipoprotein, and prevents the accumulation of oxidized lipids in low-density lipoproteins in vitro. Common polymorphisms in genes encoding paraoxonase are established risk factors in a variety of vascular disorders including coronary artery disease and carotid artery stenosis, but their association with Alzheimer disease (AD) is controversial. We tested the association of 29 SNPs in PON1, PON2 and PON3 with AD in 730 Caucasian and 467 African American participants of the MIRAGE Study, an ongoing multi-center family-based genetic epidemiology study of AD. Eight SNPs were associated with AD in the African American families (0.0001 <= P <= 0.04) and two SNPs were associated with AD in Caucasian families (0.01 <= P <= 0.04). Of note, the pattern of association for the PON1 promoter SNP -161[C/T] was the same in both ethnic groups (P=0.006). Haplotype analysis using sliding windows revealed 11 contiguous SNP combinations spanning the three PON genes with significant global test scores (0.006 <= P <= 0.04) in the two ethnic groups combined. The most significantly associated haplotype comprised SNPs in the region spanning the -161[C/T] SNP (P=0.00009). Our results demonstrate association between AD and variants in the PON gene cluster in Caucasians and African Americans.
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页码:77 / 85
页数:9
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