Effects of the diabetes linked TCF7L2 polymorphism in a representative older population

David Melzer, Anna Murray, Alison J. Hurst, Michael N. Weedon, Stefania Bandinelli, Anna Maria Corsi, Luigi Ferrucci, Guiseppe Paolisso, Jack M. Guralnik, Timothy M. Frayling

Research output: Contribution to journalArticle

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 ≥ 65 years from the population representative InCHIANTI study were enrolled in this study. Those with fasting blood glucose of ≥ 7 mmol/l or physician diagnosis were considered diabetic. Cut-off points for impaired fasting glucose (IFG) were ≥ 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). Conclusion: The TCF7L2 rs790314 6 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.

Original languageEnglish (US)
Article number34
JournalBMC Medicine
Volume4
DOIs
StatePublished - 2006
Externally publishedYes

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T Cell Transcription Factor 1
Fasting
Alleles
Population
Glucose
Waist Circumference
Blood Glucose
Insulin
Physicians
Lipids
Diabetes Complications
Type 2 Diabetes Mellitus
HDL Cholesterol
Dementia
Case-Control Studies
Creatinine
Triglycerides
Myocardial Infarction
Genotype
Confidence Intervals

ASJC Scopus subject areas

  • Medicine(all)
  • Public Health, Environmental and Occupational Health

Cite this

Melzer, D., Murray, A., Hurst, A. J., Weedon, M. N., Bandinelli, S., Corsi, A. M., ... Frayling, T. M. (2006). Effects of the diabetes linked TCF7L2 polymorphism in a representative older population. BMC Medicine, 4, [34]. https://doi.org/10.1186/1741-7015-4-34

Effects of the diabetes linked TCF7L2 polymorphism in a representative older population. / Melzer, David; Murray, Anna; Hurst, Alison J.; Weedon, Michael N.; Bandinelli, Stefania; Corsi, Anna Maria; Ferrucci, Luigi; Paolisso, Guiseppe; Guralnik, Jack M.; Frayling, Timothy M.

In: BMC Medicine, Vol. 4, 34, 2006.

Research output: Contribution to journalArticle

Melzer, D, Murray, A, Hurst, AJ, Weedon, MN, Bandinelli, S, Corsi, AM, Ferrucci, L, Paolisso, G, Guralnik, JM & Frayling, TM 2006, 'Effects of the diabetes linked TCF7L2 polymorphism in a representative older population', BMC Medicine, vol. 4, 34. https://doi.org/10.1186/1741-7015-4-34
Melzer, David ; Murray, Anna ; Hurst, Alison J. ; Weedon, Michael N. ; Bandinelli, Stefania ; Corsi, Anna Maria ; Ferrucci, Luigi ; Paolisso, Guiseppe ; Guralnik, Jack M. ; Frayling, Timothy M. / Effects of the diabetes linked TCF7L2 polymorphism in a representative older population. In: BMC Medicine. 2006 ; Vol. 4.
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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 ≥ 65 years from the population representative InCHIANTI study were enrolled in this study. Those with fasting blood glucose of ≥ 7 mmol/l or physician diagnosis were considered diabetic. Cut-off points for impaired fasting glucose (IFG) were ≥ 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). Conclusion: The TCF7L2 rs790314 6 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.",
author = "David Melzer and Anna Murray and Hurst, {Alison J.} and Weedon, {Michael N.} and Stefania Bandinelli and Corsi, {Anna Maria} and Luigi Ferrucci and Guiseppe Paolisso and Guralnik, {Jack M.} and Frayling, {Timothy M.}",
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T1 - Effects of the diabetes linked TCF7L2 polymorphism in a representative older population

AU - Melzer, David

AU - Murray, Anna

AU - Hurst, Alison J.

AU - Weedon, Michael N.

AU - Bandinelli, Stefania

AU - Corsi, Anna Maria

AU - Ferrucci, Luigi

AU - Paolisso, Guiseppe

AU - Guralnik, Jack M.

AU - Frayling, Timothy M.

PY - 2006

Y1 - 2006

N2 - 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 ≥ 65 years from the population representative InCHIANTI study were enrolled in this study. Those with fasting blood glucose of ≥ 7 mmol/l or physician diagnosis were considered diabetic. Cut-off points for impaired fasting glucose (IFG) were ≥ 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). Conclusion: The TCF7L2 rs790314 6 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.

AB - 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 ≥ 65 years from the population representative InCHIANTI study were enrolled in this study. Those with fasting blood glucose of ≥ 7 mmol/l or physician diagnosis were considered diabetic. Cut-off points for impaired fasting glucose (IFG) were ≥ 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). Conclusion: The TCF7L2 rs790314 6 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.

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