Effects of the diabetes linked TCF7L2 polymorphism in a representative older population.
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.
Melzer
David
D
Peninsula Medical School, RD&E Wonford Site, Barrack Road, Exeter, EX2 5DW, UK. david.melzer@pms.ac.uk
Murray
Anna
A
Hurst
Alison J
AJ
Weedon
Michael N
MN
Bandinelli
Stefania
S
Corsi
Anna Maria
AM
Ferrucci
Luigi
L
Paolisso
Guiseppe
G
Guralnik
Jack M
JM
Frayling
Timothy M
TM
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
D007328:Insulin; D008055:Lipids; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein