title: Effects of the diabetes linked TCF7L2 polymorphism in a representative older population.
abstract: BACKGROUND
  A polymorphism in the transcription factor 7-like 2 (TCF7L2) gene has been found to be associated with type 2 diabetes in case-control studies. We aimed to estimate associations of the marker rs7903146 (C/T) polymorphism with fasting glucose, lipids, diabetes prevalence and complications in an older general population.
  
  
  METHODS
  In total, 944 subjects aged > or = 65 years from the population representative InCHIANTI study were enrolled in this study. Those with fasting blood glucose of > or = 7 mmol/l or physician diagnosis were considered diabetic. Cut-off points for impaired fasting glucose (IFG) were > or = 5.6 mmol/l to < 7 mmol/l.
  
  
  RESULTS
  In the general population sample, minor (T) allele carriers of rs7903146 had higher fasting blood glucose (FBG) (p = 0.028) but lower fasting insulin (p = 0.030) and HOMA2b scores (p = 0.001), suggesting poorer beta-cell function. T allele carriers also had smaller waist circumference (p = 0.009), lower triglyceride levels (p = 0.006), and higher high-density lipoprotein cholesterol (p = 0.008). The prevalence of diabetes or IFG was 32.4% in TT carriers and 23.3% in CC carriers; adjusted OR = 1.67 (95% confidence interval 1.05 to 2.65, p = 0.031). Within the diabetic and IFG groups, fewer T allele carriers had metabolic syndrome features (p = 0.047) or had experienced a myocardial infarction (p = 0.037). Conversely, T allele carriers with diabetes had poorer renal function (reduced 24-hour creatinine clearance, p = 0.013), and possibly more retinopathy (p = 0.067). Physician-diagnosed dementia was more common in the T carriers (in diabetes p = 0.05, with IFG p = 0.024).
  
  
  CONCLUSIONS
  The TCF7L2 rs7903146 polymorphism is associated with lower insulin levels, smaller waist circumference, and lower risk lipid profiles in the general elderly population. Patients with diabetes who are carriers of the minor allele are less likely to have metabolic-syndrome features, but may experience more microvascular complications, although the number of cases was small. If replicated, these findings may have implications for developing treatment approaches tailored by genotype.
authors.affiliation: Peninsula Medical School, RD&E Wonford Site, Barrack Road, Exeter, EX2 5DW, UK. david.melzer@pms.ac.uk
authors.forename: David
authors.initials: D
authors.lastname: Melzer
authors.forename: Anna
authors.initials: A
authors.lastname: Murray
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Hurst
authors.forename: Michael N
authors.initials: MN
authors.lastname: Weedon
authors.forename: Stefania
authors.initials: S
authors.lastname: Bandinelli
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Corsi
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Guiseppe
authors.initials: G
authors.lastname: Paolisso
authors.forename: Jack M
authors.initials: JM
authors.lastname: Guralnik
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Frayling
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D049628:Body Size; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000235:genetics*; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007558:Italy; D008055:Lipids / Q000097:blood; D008297:Male; D011110:Polymorphism, Genetic; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein
chemical_list: D007328:Insulin; D008055:Lipids; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein