Influence of the Pro12Ala polymorphism of PPAR-gamma on age at onset and sRAGE levels in Alzheimer's disease. Export

@article{citeulike:6080704, 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.}, author = {Yao, Lifen and Li, Keshen and Zhang, Liming and Yao, Songpo and Piao, Zhongyuan and Song, Lin}, citeulike-article-id = {6080704}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.brainres.2009.07.034}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19631630}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19631630}, day = {29}, doi = {10.1016/j.brainres.2009.07.034}, issn = {1872-6240}, journal = {Brain research}, keywords = {age, alzheimers\_disease, biomarkers, genetics, polymorphism, ppar-gamma, srage}, month = {September}, pages = {133--139}, posted-at = {2009-11-06 12:48:07}, priority = {3}, title = {Influence of the Pro12Ala polymorphism of PPAR-gamma on age at onset and sRAGE levels in Alzheimer's disease.}, url = {http://dx.doi.org/10.1016/j.brainres.2009.07.034}, volume = {1291}, year = {2009} }

TY - JOUR ID - citeulike:6080704 L3 - citeulike-article-id:6080704 N2 - 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. JF - Brain research SN - 1872-6240 EP - 139 TI - Influence of the Pro12Ala polymorphism of PPAR-gamma on age at onset and sRAGE levels in Alzheimer's disease. VL - 1291 SP - 133 KW - age KW - alzheimers_disease KW - biomarkers KW - genetics KW - polymorphism KW - ppar-gamma KW - srage AU - Yao, Lifen AU - Li, Keshen AU - Zhang, Liming AU - Yao, Songpo AU - Piao, Zhongyuan AU - Song, Lin PY - 2009/09/29/ UR - http://dx.doi.org/10.1016/j.brainres.2009.07.034 ER -