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Desmoglein-2 precursor (Cadherin family member 5) (HDGC) [CDHF5]


Association and interaction effects of Alzheimer's disease-associated genes and lifestyle on cognitive aging in older adults in a Taiwanese population.

Genome-wide association studies and meta-analyses implicated that increased risk of developing Alzheimer's diseases (AD) has been associated with the ABCA7, APOE, BIN1, CASS4, CD2AP, CD33, CELF1, CLU, CR1, DSG2, EPHA1, FERMT2, HLA-DRB1, HLA-DRB4, INPP5D, MEF2C, MS4A4A, MS4A4E, MS4A6E, NME8, PICALM, PLD3, PTK2B, RIN3, SLC24A4, SORL1, and ZCWPW1 genes. In this study, we assessed whether single nucleotide polymorphisms (SNPs) within these 27 AD-associatedgenes are linked with cognitive aging independently and/or through complex interactions in an older Taiwanese population. We also analyzed the interactions between lifestyle and these genes in influencing cognitive aging. A total of 634 Taiwanese subjects aged over 60 years from the Taiwan Biobank were analyzed. Mini-Mental State Examination (MMSE) scores were performed for all subjects to evaluate cognitive functions. Out of the 588 SNPs tested in this study, only the association between CASS4-rs911159 and cognitive aging persisted significantly (P = 2.2 x 10-5) after Bonferroni correction. Our data also showed a nominal association of cognitive aging with the SNPs in six more key AD-associated genes, including EPHA1-rs10952552, FERMT2-rs4901317, MEF2C-rs9293506, PLD3-rs11672825, RIN3-rs1885747, and SLC24A4-rs67063100 (P = 0.0018~0.0097). Additionally, we found the interactions among CASS4-rs911159, EPHA-rs10952552, FERMT2-rs4901317, MEF2C-rs9293506, or SLC24A4-rs67063100 on cognitive aging (P = 0.004~0.035). Moreover, our analysis suggested the interactions of SLC24A4-rs67063100 or MEF2C-rs9293506 with lifestyle such as alcohol consumption, smoking status, physical activity, or social support on cognitive aging (P = 0.008~0.041). Our study indicates that the AD-associated genes may contribute to the risk of cognitive aging independently as well as through gene-gene and gene-lifestyle interactions.

MeSH Terms

  • Age Factors
  • Aged
  • Alleles
  • Alzheimer Disease
  • Cognitive Aging
  • Epistasis, Genetic
  • Female
  • Gene-Environment Interaction
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Life Style
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Taiwan


  • Alzheimer’s diseases
  • Gerotarget
  • Mini-Mental State Examination
  • cognitive aging
  • gene-gene and gene-lifestyle interactions
  • single nucleotide polymorphisms

Age-dependent clinical and genetic characteristics in Japanese patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia.

 Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a heart muscle disease caused by desmosomal gene mutations, and presents as ventricular tachycardia and sudden cardiac death. Although the mean age at onset or diagnosis of ARVC/D are reported to be around the 30-40s, the age-dependent clinical and genetic differences remain unknown.  A total of 35 consecutive Japanese probands (23 male) who were clinically diagnosed with ARVC/D were enrolled in the present study, and genetic analysis of PKP2, DSP, DSG2, and DSC2 was done. The mean age at the first symptom and at diagnosis was 38.6±14.8 years and 40.5±17.7 years, respectively. Probands in whom the onset was cardiopulmonary arrest were significantly younger (22.3±15.3 years) than those with arrhythmia (41.1±13.2 years) or congestive heart failure (45.7±8.5 years). On genetic screening, 19 mutation carriers were identified. Although there was no age dependence for each gene mutation carrier, carriers with PKP2 premature stop codon developed the disease at a significantly younger age than other mutation carriers.  The initial clinical manifestations in some young probands were very severe, and PKP2 mutations with a premature stop codon would be associated with disease onset at a younger age. 

MeSH Terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aging
  • Arrhythmogenic Right Ventricular Dysplasia
  • Asian Continental Ancestry Group
  • Desmocollins
  • Desmoglein 2
  • Desmoplakins
  • Female
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Mutation
  • Plakophilins