title: Age-Based Differences in the Genetic Determinants of Glycemic Control: A Case of FOXO3 Variations.
abstract: BACKGROUND
  Glucose homeostasis is a trait of healthy ageing and is crucial to the elderly, but less consideration has been given to the age composition in most studies involving genetics and hyperglycemia.
  
  
  METHODS
  Seven variants in FOXO3 were genotyped in three cohorts (n = 2037; LLI, MI_S and MI_N; mean age: 92.5 ± 3.6, 45.9 ± 8.2 and 46.8 ± 10.3, respectively) to compare the contribution of FOXO3 to fasting hyperglycemia (FH) between long-lived individuals (LLI, aged over 90 years) and middle-aged subjects (aged from 35-65 years).
  
  
  RESULTS
  A different genetic predisposition of FOXO3 alleles to FH was observed between LLI and both of two middle-aged cohorts. In the LLI cohort, the longevity beneficial alleles of three variants with the haplotype "AGGC" in block 1 were significantly protective to FH, fasting glucose, hemoglobin A1C and HOMA-IR. Notably, combining multifactor dimensionality reduction and logistic regression, we identified a significant 3-factor interaction model (rs2802288, rs2802292 and moderate physical activity) associated with lower FH risk. However, not all of the findings were replicated in the two middle-aged cohorts.
  
  
  CONCLUSIONS
  Our data provides a novel insight into the inconsistent genetic determinants between middle-aged and LLI subjects. FOXO3 might act as a shared genetic predisposition to hyperglycemia and lifespan.
authors.affiliation: The key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Neurology, Jiangbin Hospital, Nanning, Guangxi, China.
authors.forename: Caiyou
authors.initials: C
authors.lastname: Hu
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Department of Cardiothoracic Surgery, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, China.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Department of Neurology, Jiangbin Hospital, Nanning, Guangxi, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Liang
authors.affiliation: Department of Neurology, Jiangbin Hospital, Nanning, Guangxi, China.
authors.forename: Zeping
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Office of longevity cultural, People's government of Yongfu County, Yongfu, Guangxi, China.
authors.forename: Zezhi
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Lab of Genetics and Metabolism, Beijing Obstetrics and Gynecology Hospital, Beijing, China.
authors.forename: Keyan
authors.initials: K
authors.lastname: Qi
authors.affiliation: Department of obstetrics, Beijing Shunyi Airport Hospital, Beijing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Neurology, Jiangbin Hospital, Nanning, Guangxi, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: The key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing, China.
authors.forename: Ze
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism; D003430:Cross-Sectional Studies; D005215:Fasting; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000097:blood / Q000235:genetics*; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006442:Glycated Hemoglobin / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000235:genetics*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D016015:Logistic Models; D008136:Longevity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D058011:Multifactor Dimensionality Reduction
chemical_list: D001786:Blood Glucose; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D006442:Glycated Hemoglobin; D007328:Insulin; C499517:FOXO3 protein, human; C517652:hemoglobin A1c protein, human