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

Yao, Lifen; Li, Keshen; Zhang, Liming; Yao, Songpo; Piao, Zhongyuan; Song, Lin

doi:10.1016/j.brainres.2009.07.034

Cited by 18 publications

(11 citation statements)

References 32 publications

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“…Functional polymorphism in PPARG gene has been also related to AD, but study results are conflicting [68][69][70][71]. Interestingly, it was recently suggested that the functional PPARG Pro12Ala polymorphism may modify the onset of age of AD [72]. Previous reports showed that the PPARG Ala allele was associated with cognitive function [73].…”

Section: Genetic Polymorphisms Associated With Risk Of Alzheimer's DImentioning

confidence: 99%

Genome-Wide Association Studies: Is there a Genotype for Cognitive Decline in Older Persons with Type 2 Diabetes?

Abbatecola¹,

Olivieri²,

Corsonello³

et al. 2011

Current Pharmaceutical Design

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There is a dramatic increase in the number of elderly persons on a worldwide scale with an increase in chronic comorbidities, especially type 2 diabetes (T2DM) and dementia. Although cognitive faculties commonly deteriorate in non-diabetic persons as they age, several studies have concluded that diabetes is uniquely associated with cognitive decline and is associated with a two-fold risk of Alzheimer's Disease (AD). Studies have also suggested that good glycemic has shown to improve cognitive status, however whether the use of specific anti-diabetic oral agents may play an additional role in controlling against cognitive deterioration is unknown. In addition, excitotoxicity from the overstimulation of glutamate receptors is considered a major cause of neuron death in AD and statins may be promising agents for protecting against memory loss. Possible pathophysiologic mechanisms common to both T2DM and AD are glucose toxicity and a direct effect of insulin on amyloid metabolism. In fact, AD and T2DM have comparable pathological features in the islet and brain (amyloid derived from amyloid β protein (β-amyloid) in the brain in AD and islet amyloid derived from islet amyloid polypeptide in the pancreas in T2DM). Evidence is growing linking precursors of amyloid deposition in the brain and pancreas to the pathogenesis of AD and T2DM, respectively. Indeed, the need to identify agents capable of correcting such pathological features may in turn significantly protect against the accumulation of β-amyloid in the brain, known to interfere with correct cognitive function. Cholesterol may also be directly involved in β-amyloid aggregation: abnormal oxidative metabolites such as cholesterol-derived aldehydes can modify β-amyloid, firstly promoting Schiff base formation, then accelerating the early stages of amyloidogenesis. At the moment, genome-wide association studies (GWAS) have begun to elucidate the genetic architecture of chronic diseases including, T2DM and AD. Thus, one of the challenges for a successful GWAS in the future will be to identify a genotype in older persons with T2DM for good drug response, which in turn may protect against cognitive decline and AD. The literature has suggested that the use of insulin sensitizers and statins is correlated with a lower rate of cognitive decline in older persons. In this paper, we will explore recent findings regarding diverse single nucleotide polymorphisms from GWAS on T2DM, AD and both. We will also shed light on future pathways, as the basis of improving drug and diagnostics development for a better integration of genetic studies for precise drug-development focusing on the role of genetic variation in maintaining metabolic control and cognitive performance.

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Section: Genetic Polymorphisms Associated With Risk Of Alzheimer's DImentioning

confidence: 99%

Genome-Wide Association Studies: Is there a Genotype for Cognitive Decline in Older Persons with Type 2 Diabetes?

Abbatecola¹,

Olivieri²,

Corsonello³

et al. 2011

Current Pharmaceutical Design

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“…The Ala12 allele frequency of the Pro12Ala SNP varies widely among continental and ethnic groups; reported Ala12 allele frequencies include 0.15 in a Finnish population, 0.12 in a German population, 0.082 in an Italian population, and 0.034 in a Chinese population [30]. In the context of sepsis, this variation might result in diverse genetic roles of this polymorphism in different populations.…”

Section: Discussionmentioning

confidence: 99%

The Pro12Ala Polymorphism of PPAR-γGene Is Associated with Sepsis Disease Severity and Outcome in Chinese Han Population

Wang

et al. 2014

PPAR Research

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Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a ligand-binding nuclear receptor, and its activation plays a prominent role in regulating the inflammatory response. Therefore, PPAR-γ has been suggested as a candidate gene for sepsis. In the present study, we investigated the association between the Pro12Ala polymorphism of PPAR-γ and sepsis in a Han Chinese population. A total of 308 patients with sepsis and 345 healthy controls were enrolled in this study. Genotyping was performed using the polymerase chain reaction-ligation detection reaction (PCR-LDR) method. No significant differences were detected in the allele and genotype distributions of the PPAR-γ Pro12Ala SNP between septic patients and controls (P = 0.622 for genotype; P = 0.629 for allele). However, stratification by subtypes (sepsis, septic shock, and severe sepsis) revealed a statistically significant difference in the frequency of the Ala allele and Ala-carrier genotype between the patients with the sepsis subtype and the healthy controls (P = 0.014 for allele and P = 0.012, for genotype). Moreover, significant differences were found in the frequency of the Ala allele and genotype between the sepsis survivors and nonsurvivors (all P = 0.002). In the survivors, the PPAR-γ Pro12Ala genotype was significantly associated with decreased disease severity and recovery time (all P < 0.001). Thus, genetic polymorphism is thought to play a role in the development and outcome of sepsis.

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“…After full-text review, one study was excluded, because the study was a review. A total of eight studies met all the inclusion criteria and were considered in our meta-analysis, comprising 2948 patients with AD and 3753 controls (Sauder et al, 2005;Koivisto et al, 2006;Hamilton et al, 2007;Scacchi et al, 2007;Helisalmi et al, 2008;Yao et al, 2009;Combarros et al, 2011;Shibata et al, 2013). Eight studies (seven European, one Asian) with 3501 cases and 4622 controls considered the PPARg Pro12Ala polymorphism, and three studies (three European) with 553 cases and 869 controls considered the PPARg His447His polymorphism.…”

Section: Studies Included In the Meta-analysismentioning

confidence: 99%

“…The PPARg Pro12Ala and His447His polymorphisms have been studied in the context of AD (Sauder et al, 2005;Koivisto et al, 2006;Hamilton et al, 2007;Scacchi et al, 2007;Helisalmi et al, 2008;Yao et al, 2009;Combarros et al, 2011;Shibata et al, 2013). However, published results on the genetic associations of these PPARg polymorphisms are controversial and inconclusive.…”

Section: Introductionmentioning

confidence: 99%

PPARγ Pro12Ala and His447His polymorphisms and susceptibility to Alzheimer’s disease: a meta-analysis

Lee¹,

Song²

2015

Genet. Mol. Res.

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ABSTRACT. We investigated whether Pro12Ala (C→G) and His447His (C→T) polymorphisms of the peroxisome proliferatoractivated receptor gamma (PPARg) gene are associated with susceptibility to Alzheimer's disease (AD). We conducted a metaanalysis of the associations between the PPARg Pro12Ala and His447His polymorphisms and AD in subjects. The meta-analysis was performed according to the apolipoprotein E (APOE) ɛ4 allele status. A total of eight studies were considered in our meta-analysis, comprising 2948 patients with AD and 3753 controls. Meta-analysis showed no association between AD and the PPARg Pro12Ala G allele in any of the study subjects [odds ratio (OR) = 1.013, 95% confidence interval (95%CI) = 0.906-1.132, P = 0.821] or in the European and Asian populations (OR = 0.997, 95%CI = 0.890-1.118, P = 0.965; OR = 1.409, 95%CI = 0.832-2.387, P = 0.202, respectively). We tested whether the APOE ɛ4 allele affects the association between the PPARg Pro12Ala polymorphism and AD. Meta-analysis showed no association between AD and the PPARg G allele in any of the study subjects with or without the APOE ɛ4 allele. Meta-analysis showed no association between AD and the PPARg His447His T allele in the European population (OR for T allele = 0.912, 95%CI = 0.732-1.136, P = 0.409). This meta-analysis has shown that there is a lack of association between the PPARg Pro12Ala and His447His polymorphisms and AD risk.

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

Cited by 18 publications

References 32 publications

Genome-Wide Association Studies: Is there a Genotype for Cognitive Decline in Older Persons with Type 2 Diabetes?

Genome-Wide Association Studies: Is there a Genotype for Cognitive Decline in Older Persons with Type 2 Diabetes?

The Pro12Ala Polymorphism of PPAR-γGene Is Associated with Sepsis Disease Severity and Outcome in Chinese Han Population

PPARγ Pro12Ala and His447His polymorphisms and susceptibility to Alzheimer’s disease: a meta-analysis

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