PPARG
Peroxisome proliferator-activated receptor gamma (PPAR-gamma) (Nuclear receptor subfamily 1 group C member 3) [NR1C3]
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Previous reports suggest race/ethnic and sex heterogeneity in the association between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma (PPARG) gene and cognitive decline. Tests of verbal memory, processing speed, and verbal fluency and a composite global Z-score were used to assess cognitive performance longitudinally in a large (n=11,620) biracial cohort of older adults in the Atherosclerosis Risk in Communities Neurocognitive Study from midlife to older age. Linear mixed models were used to estimate associations between the Ala12 allele and cognitive performance over 20 years of follow-up. Heterogeneity was present for rate of cognitive decline as measured by the global Z-score by race, sex, and Ala12 allele status (P=0.01 for 4-way interaction term: race×sex×time×Ala12 carrier status). Stratified analysis showed a significantly increased rate of global cognitive decline over the 20-year follow-up for carriers of the Ala12 allele compared with noncarriers among black male individuals (-0.92 SD decline vs. -0.57 SD; P=0.02) but not among black female, white male, or white female individuals. Decline in global cognitive function among black male Ala12 carriers was primarily driven by decline in verbal memory. Our data underscore the context-dependent association between the Pro12Ala polymorphism and cognitive decline, specifically race/ethnic background and sex.
MeSH Terms
- African Americans
- Alleles
- Cognitive Aging
- Cognitive Dysfunction
- European Continental Ancestry Group
- Female
- Genetic Predisposition to Disease
- Genotype
- Humans
- Longitudinal Studies
- Male
- Middle Aged
- Neuropsychological Tests
- PPAR gamma
- Polymorphism, Genetic
- Prospective Studies
- Sex Factors
Evidence indicates that the pathophysiologic mechanisms associated with insulin resistance may contribute to cognitive aging and Alzheimer's diseases. In this study, we hypothesize that single nucleotide polymorphisms (SNPs) within insulin resistance-associated genes, such as the ADAM metallopeptidase with thrombospondin type 1 motif 9 (ADAMTS9), glucokinase regulator (GCKR), and peroxisome proliferator activated receptor gamma (PPARG) genes, may be linked with cognitive aging independently and/or through complex interactions in an older Taiwanese population. A total of 547 Taiwanese subjects aged over 60 years from the Taiwan Biobank were analyzed. Mini-Mental State Examinations (MMSE) were administered to all subjects, and MMSE scores were used to measure cognitive functions. Our data showed that four SNPs (rs73832338, rs9985304, rs4317088, and rs9831846) in the ADAMTS9 gene were significantly associated with cognitive aging among the subjects (P = 1.5 x 10-6 ~ 0.0002). This association remained significant after performing Bonferroni correction. Additionally, we found that interactions between the ADAMTS9 rs9985304 and ADAMTS9 rs76346246 SNPs influenced cognitive aging (P < 0.001). However, variants in the GCKR and PPARG genes had no association with cognitive aging in our study. Our study indicates that the ADAMTS9 gene may contribute to susceptibility to cognitive aging independently as well as through SNP-SNP interactions.
MeSH Terms
- ADAMTS9 Protein
- Adaptor Proteins, Signal Transducing
- Aged
- Aged, 80 and over
- Cognitive Aging
- Databases, Genetic
- Female
- Genetic Association Studies
- Genotype
- Humans
- Male
- Middle Aged
- Neuropsychological Tests
- PPAR gamma
- Polymorphism, Single Nucleotide
- Taiwan
Genotype and allele frequencies of uncoupling proteins 2 and 3 genes (UCP2 and UCP3) and peroxisome proliferator-activated receptors genes (PPARA, PPARD and PPARG) were studied in 206 residents of the siege and in 139 individuals of more than 69 years old (control group). Studied polymorphisms included UCP2 (Ala55Val), UCP3 (C-55T), PPARA (G/C), PPARD ( 294T/C), and PPARG (Pro12Ala). The G allele and the G/G genotype (PPARA) were overrepresented in the group of survivors and C/C (UCP3) genotype prevailed in the women of besieged Leningrad compared to relevant control groups of the persons of the same age who did not suffered hungry disaster. Feasible protective effects of PPARA gene allele G and C allele of UCP2 genes are briefly discussed.
MeSH Terms
- Aged
- Aged, 80 and over
- Case-Control Studies
- Cities
- Data Interpretation, Statistical
- Female
- Gene Frequency
- Genotype
- Humans
- Ion Channels
- Longevity
- Male
- Malnutrition
- Mitochondrial Proteins
- PPAR alpha
- PPAR delta
- PPAR gamma
- Polymorphism, Single Nucleotide
- Russia
- Survivors
- Uncoupling Protein 2
- Uncoupling Protein 3
- World War II