Skip to main content
Top
Published in: BMC Endocrine Disorders 1/2010

Open Access 01-12-2010 | Research article

The transcription factor 7-like 2 (TCF7L2) polymorphism may be associated with focal arteriolar narrowing in Caucasians with hypertension or without diabetes: the ARIC Study

Authors: Yu Yan, Ronald Klein, Gerardo Heiss, Cynthia J Girman, Ethan M Lange, Barbara E Klein, Kathryn M Rose, Eric Boerwinkle, James S Pankow, Frederick L Brancati, Christie M Ballantyne, Anna Köttgen, Kari E North

Published in: BMC Endocrine Disorders | Issue 1/2010

Login to get access

Abstract

Background

Transcription factor 7-like 2 (TCF7L2) has emerged as a consistently replicated susceptibility gene for type 2 diabetes, however, whether the TCF7L2 gene also has similar effects on the retinal microvasculature is less clear. We therefore aimed to investigate the association between the transcription factor 7-like 2 (TCF7L2) rs7903146 polymorphism and retinal microvascular phenotypes in the Atherosclerosis Risk in Communities (ARIC) Study (1993-1995).

Methods

This was a population-based, cross-sectional study of 10,320 middle-aged African American (n = 2,199) and Caucasian (n = 8,121) men and women selected from four United States communities to examine the association between TCF7L2 rs7903146 polymorphism and retinal microvascular signs (retinopathy, focal arteriolar narrowing, arteriovenous nicking, arteriolar and venular calibers). Photographs on one randomly selected eye were graded for presence of retinal microvascular signs and used to measure retinal vessel calibres.

Results

After adjusting for age, sex, study center, mean arterial blood pressure, total serum cholesterol, triglycerides, and other covariates, few associations of TCF7L2 rs7903146 and retinal microvascular signs were noted. TCF7L2 rs7903146 T risk allele was significantly associated with focal arteriolar narrowing in Caucasians with hypertension [odds ratio (OR)CT vs. CC (95% CI) = 1.25 (1.09-1.44); ORTT vs. CC = 1.56 (1.18-2.06); P = 0.002] and in Caucasians without diabetes [OR CT vs. CC = 1.18 (1.06-1.32); OR TT vs. CC = 1.40 (1.12, 1.75); P = 0.003]. No significant association of the TCF7L2 rs7903146 polymorphism and retinal vascular signs was noted among African American individuals.

Conclusions

TCF7L2 rs7903146 is not consistently associated with retinal microvascular signs. However, we report an association between the TCF7L2 rs7903146 polymorphism and focal arteriolar narrowing in Caucasians with hypertension or without diabetes. Further research in other large, population-based studies is needed to replicate these findings.
Appendix
Available only for authorised users
Literature
1.
go back to reference Wong TY, Klein R, Klein BE, Tielsch JM, Hubbard L, Nieto FJ: Retinal microvascular abnormalities and their relationship with hypertension, cardiovascular disease, and mortality. Surv Ophthalmol. 2001, 46: 59-80. 10.1016/S0039-6257(01)00234-X.CrossRefPubMed Wong TY, Klein R, Klein BE, Tielsch JM, Hubbard L, Nieto FJ: Retinal microvascular abnormalities and their relationship with hypertension, cardiovascular disease, and mortality. Surv Ophthalmol. 2001, 46: 59-80. 10.1016/S0039-6257(01)00234-X.CrossRefPubMed
2.
go back to reference Sun C, Wang JJ, Mackey DA, Wong TY: Retinal vascular caliber: systemic, environmental, and genetic associations. Surv Ophthalmol. 2009, 54: 74-95. 10.1016/j.survophthal.2008.10.003.CrossRefPubMed Sun C, Wang JJ, Mackey DA, Wong TY: Retinal vascular caliber: systemic, environmental, and genetic associations. Surv Ophthalmol. 2009, 54: 74-95. 10.1016/j.survophthal.2008.10.003.CrossRefPubMed
3.
go back to reference Nguyen TT, Wang JJ, Sharrett AR, Islam FM, Klein R, Klein BE, Cotch MF, Wong TY: Relationship of retinal vascular caliber with diabetes and retinopathy: the Multi-Ethnic Study of Atherosclerosis (MESA). Diabetes Care. 2008, 31: 544-549. 10.2337/dc07-1528.CrossRefPubMed Nguyen TT, Wang JJ, Sharrett AR, Islam FM, Klein R, Klein BE, Cotch MF, Wong TY: Relationship of retinal vascular caliber with diabetes and retinopathy: the Multi-Ethnic Study of Atherosclerosis (MESA). Diabetes Care. 2008, 31: 544-549. 10.2337/dc07-1528.CrossRefPubMed
4.
go back to reference Wang JJ, Wong TY: Genetic determinants of retinal vascular caliber: additional insights into hypertension pathogenesis. Hypertension. 2006, 47: 644-645. 10.1161/01.HYP.0000208303.74884.78.CrossRefPubMed Wang JJ, Wong TY: Genetic determinants of retinal vascular caliber: additional insights into hypertension pathogenesis. Hypertension. 2006, 47: 644-645. 10.1161/01.HYP.0000208303.74884.78.CrossRefPubMed
5.
go back to reference Xing C, Klein BE, Klein R, Jun G, Lee KE, Iyengar SK: Genome-wide linkage study of retinal vessel diameters in the Beaver Dam Eye Study. Hypertension. 2006, 47: 797-802. 10.1161/01.HYP.0000208330.68355.72.CrossRefPubMed Xing C, Klein BE, Klein R, Jun G, Lee KE, Iyengar SK: Genome-wide linkage study of retinal vessel diameters in the Beaver Dam Eye Study. Hypertension. 2006, 47: 797-802. 10.1161/01.HYP.0000208330.68355.72.CrossRefPubMed
6.
go back to reference Grant SF, Thorleifsson G, Reynisdottir I, Benediktsson R, Manolescu A, Sainz J, Helgason A, Stefansson H, Emilsson V, Helgadottir A: Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. NatGenet. 2006, 38: 320-323. Grant SF, Thorleifsson G, Reynisdottir I, Benediktsson R, Manolescu A, Sainz J, Helgason A, Stefansson H, Emilsson V, Helgadottir A: Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. NatGenet. 2006, 38: 320-323.
7.
go back to reference Yan Y, North KE, Ballantyne CM, Brancati FL, Chambless LE, Franceschini N, Heiss G, Kottgen A, Pankow JS, Selvin E: Transcription Factor 7-Like 2 (TCF7L2) Polymorphism and Context-Specific Risk of Type 2 Diabetes in African American and Caucasian Adults: The Atherosclerosis Risk in Communities (ARIC) Study. Diabetes. 2009, 58 (1): 285-9. 10.2337/db08-0569.CrossRefPubMedPubMedCentral Yan Y, North KE, Ballantyne CM, Brancati FL, Chambless LE, Franceschini N, Heiss G, Kottgen A, Pankow JS, Selvin E: Transcription Factor 7-Like 2 (TCF7L2) Polymorphism and Context-Specific Risk of Type 2 Diabetes in African American and Caucasian Adults: The Atherosclerosis Risk in Communities (ARIC) Study. Diabetes. 2009, 58 (1): 285-9. 10.2337/db08-0569.CrossRefPubMedPubMedCentral
8.
go back to reference Cauchi S, El Achhab Y, Choquet H, Dina C, Krempler F, Weitgasser R, Nejjari C, Patsch W, Chikri M, Meyre D, Froguel P: TCF7L2 is reproducibly associated with type 2 diabetes in various ethnic groups: a global meta-analysis. J Mol Med. 2007, 85: 777-782. 10.1007/s00109-007-0203-4.CrossRefPubMed Cauchi S, El Achhab Y, Choquet H, Dina C, Krempler F, Weitgasser R, Nejjari C, Patsch W, Chikri M, Meyre D, Froguel P: TCF7L2 is reproducibly associated with type 2 diabetes in various ethnic groups: a global meta-analysis. J Mol Med. 2007, 85: 777-782. 10.1007/s00109-007-0203-4.CrossRefPubMed
9.
go back to reference Cauchi S, Froguel P: TCF7L2 genetic defect and type 2 diabetes. Curr Diab Rep. 2008, 8: 149-155. 10.1007/s11892-008-0026-x.CrossRefPubMed Cauchi S, Froguel P: TCF7L2 genetic defect and type 2 diabetes. Curr Diab Rep. 2008, 8: 149-155. 10.1007/s11892-008-0026-x.CrossRefPubMed
10.
go back to reference Cauchi S, Meyre D, Dina C, Choquet H, Samson C, Gallina S, Balkau B, Charpentier G, Pattou F, Stetsyuk V: Transcription factor TCF7L2 genetic study in the French population: expression in human beta-cells and adipose tissue and strong association with type 2 diabetes. Diabetes. 2006, 55: 2903-2908. 10.2337/db06-0474.CrossRefPubMed Cauchi S, Meyre D, Dina C, Choquet H, Samson C, Gallina S, Balkau B, Charpentier G, Pattou F, Stetsyuk V: Transcription factor TCF7L2 genetic study in the French population: expression in human beta-cells and adipose tissue and strong association with type 2 diabetes. Diabetes. 2006, 55: 2903-2908. 10.2337/db06-0474.CrossRefPubMed
11.
go back to reference Melzer D, Murray A, Hurst AJ, Weedon MN, Bandinelli S, Corsi AM, Ferrucci L, Paulisso G, Guralnik JM, Frayling TM: Effects of the diabetes linked TCF7L2 polymorphism in a representative older population. BMC Med. 2006, 4: 34-10.1186/1741-7015-4-34.CrossRefPubMedPubMedCentral Melzer D, Murray A, Hurst AJ, Weedon MN, Bandinelli S, Corsi AM, Ferrucci L, Paulisso G, Guralnik JM, Frayling TM: Effects of the diabetes linked TCF7L2 polymorphism in a representative older population. BMC Med. 2006, 4: 34-10.1186/1741-7015-4-34.CrossRefPubMedPubMedCentral
12.
go back to reference The ARIC Investigators: The Atherosclerosis Risk in Communnities (ARIC) Study: design and objectives. Am J Epidemiol. 1989, 129: 687-702. The ARIC Investigators: The Atherosclerosis Risk in Communnities (ARIC) Study: design and objectives. Am J Epidemiol. 1989, 129: 687-702.
13.
go back to reference Hubbard LD, Brothers RJ, King WN, Clegg LX, Klein R, Cooper LS, Sharrett AR, Davis MD, Cai J: Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the Atherosclerosis Risk in Communities Study. Ophthalmology. 1999, 106: 2269-2280. 10.1016/S0161-6420(99)90525-0.CrossRefPubMed Hubbard LD, Brothers RJ, King WN, Clegg LX, Klein R, Cooper LS, Sharrett AR, Davis MD, Cai J: Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the Atherosclerosis Risk in Communities Study. Ophthalmology. 1999, 106: 2269-2280. 10.1016/S0161-6420(99)90525-0.CrossRefPubMed
14.
go back to reference Klein R, Clegg L, Cooper LS, Hubbard LD, Klein BE, King WN, Folsom AR: Prevalence of age-related maculopathy in the Atherosclerosis Risk in Communities Study. Arch Ophthalmol. 1999, 117: 1203-1210.CrossRefPubMed Klein R, Clegg L, Cooper LS, Hubbard LD, Klein BE, King WN, Folsom AR: Prevalence of age-related maculopathy in the Atherosclerosis Risk in Communities Study. Arch Ophthalmol. 1999, 117: 1203-1210.CrossRefPubMed
15.
go back to reference Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT: Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003, 42: 1206-1252. 10.1161/01.HYP.0000107251.49515.c2.CrossRefPubMed Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT: Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003, 42: 1206-1252. 10.1161/01.HYP.0000107251.49515.c2.CrossRefPubMed
16.
go back to reference Sharrett AR, Hubbard LD, Cooper LS, Sorlie PD, Brothers RJ, Nieto FJ, Pinsky JL, Klein R: Retinal Arteriolar Diameters and Elevated Blood Pressure: The Atherosclerosis Risk in Communities Study. Am J Epidemiol. 1999, 150: 263-270.CrossRefPubMed Sharrett AR, Hubbard LD, Cooper LS, Sorlie PD, Brothers RJ, Nieto FJ, Pinsky JL, Klein R: Retinal Arteriolar Diameters and Elevated Blood Pressure: The Atherosclerosis Risk in Communities Study. Am J Epidemiol. 1999, 150: 263-270.CrossRefPubMed
17.
go back to reference ADA: American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2007, 30 (Suppl 1): S42-47. ADA: American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2007, 30 (Suppl 1): S42-47.
18.
go back to reference Eckfeldt JH, Chambless LE, Shen YL: Short-term, within-person variability in clinical chemistry test results. Experience from the Atherosclerosis Risk in Communities Study. ArchPatholLab Med. 1994, 118: 496-500. Eckfeldt JH, Chambless LE, Shen YL: Short-term, within-person variability in clinical chemistry test results. Experience from the Atherosclerosis Risk in Communities Study. ArchPatholLab Med. 1994, 118: 496-500.
19.
go back to reference US Department of Health and Human Service: The practical guide-identification, evaluation, and treatment of overweight and obesity in adults. NIH publication no. 004084. 2000, Bethesda, MD: National Institutes of Health US Department of Health and Human Service: The practical guide-identification, evaluation, and treatment of overweight and obesity in adults. NIH publication no. 004084. 2000, Bethesda, MD: National Institutes of Health
20.
go back to reference Rothman KJ, Greenland S: Modern Epidemiology. 1998, Philadelphia, PA: Lippincott-Raven, 2 Rothman KJ, Greenland S: Modern Epidemiology. 1998, Philadelphia, PA: Lippincott-Raven, 2
21.
go back to reference Li R, Chambless L: Test for additive interaction in proportional hazards models. Ann Epidemiol. 2007, 17: 227-236. 10.1016/j.annepidem.2006.10.009.CrossRefPubMed Li R, Chambless L: Test for additive interaction in proportional hazards models. Ann Epidemiol. 2007, 17: 227-236. 10.1016/j.annepidem.2006.10.009.CrossRefPubMed
22.
go back to reference Greenland S: Tests for interaction in epidemiologic studies: a review and a study of power. Stat Med. 1983, 2: 243-251. 10.1002/sim.4780020219.CrossRefPubMed Greenland S: Tests for interaction in epidemiologic studies: a review and a study of power. Stat Med. 1983, 2: 243-251. 10.1002/sim.4780020219.CrossRefPubMed
23.
go back to reference Kirton JP, Crofts NJ, George SJ, Brennan K, Canfield AE: Wnt/beta-catenin signaling stimulates chondrogenic and inhibits adipogenic differentiation of pericytes: potential relevance to vascular disease?. Circ Res. 2007, 101: 581-589. 10.1161/CIRCRESAHA.107.156372.CrossRefPubMed Kirton JP, Crofts NJ, George SJ, Brennan K, Canfield AE: Wnt/beta-catenin signaling stimulates chondrogenic and inhibits adipogenic differentiation of pericytes: potential relevance to vascular disease?. Circ Res. 2007, 101: 581-589. 10.1161/CIRCRESAHA.107.156372.CrossRefPubMed
24.
go back to reference Tso MO, Jampol LM: Pathophysiology of hypertensive retinopathy. Ophthalmology. 1982, 89: 1132-1145.CrossRefPubMed Tso MO, Jampol LM: Pathophysiology of hypertensive retinopathy. Ophthalmology. 1982, 89: 1132-1145.CrossRefPubMed
25.
go back to reference Rothman KJ, Greenland S, Lash TL: Modern Epidemiology. 2008, Philadelphia, PA: Lippincott Williams & Wilkins, 3 Rothman KJ, Greenland S, Lash TL: Modern Epidemiology. 2008, Philadelphia, PA: Lippincott Williams & Wilkins, 3
Metadata
Title
The transcription factor 7-like 2 (TCF7L2) polymorphism may be associated with focal arteriolar narrowing in Caucasians with hypertension or without diabetes: the ARIC Study
Authors
Yu Yan
Ronald Klein
Gerardo Heiss
Cynthia J Girman
Ethan M Lange
Barbara E Klein
Kathryn M Rose
Eric Boerwinkle
James S Pankow
Frederick L Brancati
Christie M Ballantyne
Anna Köttgen
Kari E North
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Endocrine Disorders / Issue 1/2010
Electronic ISSN: 1472-6823
DOI
https://doi.org/10.1186/1472-6823-10-9

Other articles of this Issue 1/2010

BMC Endocrine Disorders 1/2010 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.