Research article

A role for CETP TaqIB polymorphism in determining susceptibility to atrial fibrillation: a nested case control study

Folkert W Asselbergs^1,2 , Jason H Moore³ , Maarten P van den Berg¹ , Eric B Rimm^2,4,5 , Rudolf A de Boer¹ , Robin P Dullaart⁶ , Gerjan Navis⁷ and Wiek H van Gilst^1,8

¹Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands

²Department of Nutrition, Harvard School of Public Health, Boston, MA, USA

³Computational Genetics Laboratory, Department of Genetics, Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, NH, USA

⁴Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA

⁵Channing Laboratory, Department of Medicine, Brigham & Women's Hospital, and Harvard Medical School, Boston, MA, USA

⁶Department of Endocrinology, University Medical Center Groningen, Groningen, The Netherlands

⁷Department of Nephrology, University Medical Center Groningen, Groningen, The Netherlands

⁸Department of Clinical Pharmacology, University Medical Center Groningen, Groningen, The Netherlands

author email corresponding author email

BMC Medical Genetics 2006, 7:39doi:10.1186/1471-2350-7-39

Published:	19 April 2006

Abstract

Background

Studies investigating the genetic and environmental characteristics of atrial fibrillation (AF) may provide new insights in the complex development of AF. We aimed to investigate the association between several environmental factors and loci of candidate genes, which might be related to the presence of AF.

Methods

A nested case-control study within the PREVEND cohort was conducted. Standard 12 lead electrocardiograms were recorded and AF was defined according to Minnesota codes. For every case, an age and gender matched control was selected from the same population (n = 194). In addition to logistic regression analyses, the multifactor-dimensionality reduction (MDR) method and interaction entropy graphs were used for the evaluation of gene-gene and gene-environment interactions. Polymorphisms in genes from the Renin-angiotensin, Bradykinin and CETP systems were included.

Results

Subjects with AF had a higher prevalence of electrocardiographic left ventricular hypertrophy, ischemic heart disease, hypertension, renal dysfunction, elevated levels of C-reactive protein (CRP) and increased urinary albumin excretion as compared to controls. The polymorphisms of the Renin-angiotensin system and Bradykinin gene did not show a significant association with AF (p > 0.05). The TaqIB polymorphism of the CETP gene was significantly associated with the presence of AF (p < 0.05). Using the MDR method, the best genotype-phenotype models included the combination of micro- or macroalbuminuria and CETP TaqIB polymorphism, CRP >3 mg/L and CETP TaqIB polymorphism, renal dysfunction and the CETP TaqIB polymorphism, and ischemic heart disease and CETP TaqIB polymorphism (1000 fold permutation testing, P < 0.05). Interaction entropy graph showed that the combination of albuminuria and CETP TaqIB polymorphism removed the most entropy.

Conclusion

CETP TaqIB polymorphism is significantly associated with the presence of AF in the context of micro- or macroalbuminuria, elevated C-reactive protein, renal dysfunction, and ischemic heart disease.