Polymorphisms in the PON gene cluster are associated with Alzheimer disease.
|Title||Polymorphisms in the PON gene cluster are associated with Alzheimer disease.|
|Publication Type||Journal Article|
|Year of Publication||2006|
|Authors||Erlich PM, Lunetta KL, L Cupples A, Huyck M, Green RC, Baldwin CT, Farrer LA|
|Corporate Authors||MIRAGE Study Group|
|Journal||Hum Mol Genet|
|Date Published||2006 Jan 01|
|Keywords||African Americans, Alzheimer Disease, Aryldialkylphosphatase, European Continental Ancestry Group, Gene Frequency, Humans, Linkage Disequilibrium, Multigene Family, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, United States|
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< or =P< or =0.04) and two SNPs were associated with AD in Caucasian families (0.01< or =P< or =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< or =P< or =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.
|Alternate Journal||Hum. Mol. Genet.|
|Grant List||P30-AG13846 / AG / NIA NIH HHS / United States |
R01-AG09029 / AG / NIA NIH HHS / United States
R01-HG/AG02213 / HG / NHGRI NIH HHS / United States