title: Influence of the Pro12Ala polymorphism of PPAR-gamma on age at onset and sRAGE levels in Alzheimer's disease.
abstract: Peroxisome proliferator-activated receptor gamma (PPAR-gamma) has been described to have a role in the modulation of various genes involved in Abeta homeostasis, inflammation, and energy metabolism, making it a candidate gene for risk of Alzheimer's disease (AD). A functional polymorphism in exon 2 of the PPAR-gamma gene has been related to AD, but the effects are inconsistent across studies. To determine the role of PPAR-gamma in genetic susceptibility to AD in a representative Chinese sample, we genotyped 362 AD patients and 370 healthy controls for PPAR-gamma Pro12Ala polymorphism by polymerase chain reaction-restriction fragment length polymorphism method. We also examined the potential impact of this polymorphism on plasma level of soluble receptor for advanced glycation end products (sRAGE), a decoy receptor whose reduction has been associated with a higher risk of AD. Our results suggest that PPAR-gamma Pro12Ala polymorphism was not associated with an increased risk of AD in the overall sample. Stratification analysis revealed that the PPAR-gamma Pro/Ala genotype may be associated with the development of early-onset AD in the individuals without APOE epsilon4 allele (OR=3.76, 95% CI=1.10-12.84; p=0.03), but this association became insignificant after Bonferroni correction (p (corr)=0.10). Moreover, in the subgroup of APOE epsilon4 noncarriers, Kaplan-Meier survival analyses indicated that AD patients with the Pro/Ala genotype presented with disease onset 4.6 years earlier than carriers of Pro/Pro genotype. Further investigation revealed that AD patients carrying Pro/Ala genotype had significantly lower plasma sRAGE levels than patients with Pro/Pro genotype. These findings suggest that the functional PPAR-gamma Pro12Ala polymorphism may modify the age at onset of AD.
authors.affiliation: Department of Neurology, The first affiliated hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Lifen
authors.initials: L
authors.lastname: Yao
authors.forename: Keshen
authors.initials: K
authors.lastname: Li
authors.forename: Liming
authors.initials: L
authors.lastname: Zhang
authors.forename: Songpo
authors.initials: S
authors.lastname: Yao
authors.forename: Zhongyuan
authors.initials: Z
authors.lastname: Piao
authors.forename: Lin
authors.initials: L
authors.lastname: Song
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000097:blood / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D016019:Survival Analysis
chemical_list: D047495:PPAR gamma; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic