J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M700059-JLR200 on March 24, 2007

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Journal of Lipid Research, Vol. 48, 1378-1385, June 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Genetic evidence that apolipoprotein E4 is not a relevant susceptibility factor for cholelithiasis in two high-risk populations

Juan G. Mella1,*, Ramin Schirin-Sokhan1,{dagger}, Attilio Rigotti*, Fernando Pimentel§, Luis Villarroel**, Hermann E. Wasmuth{dagger}, Tilman Sauerbruch{dagger}{dagger}, Flavio Nervi*, Frank Lammert2,{dagger},{dagger}{dagger} and Juan Francisco Miquel2,*

* Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile
{dagger} Department of Medicine III, University Hospital Aachen, Aachen University, Aachen, Germany
§ Departamento de Cirugía Digestiva, Pontificia Universidad Católica de Chile, Santiago, Chile
** Salud Pública Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
{dagger}{dagger} Department of Internal Medicine I, University Hospital Bonn, University of Bonn, Bonn, Germany

Published, JLR Papers in Press, March 24, 2007.

1 J. G. Mella and R. Schirin-Sokhan contributed equally to this work.

2 To whom correspondence should be addressed. e-mail: frank.lammert{at}ukb.uni-bonn.de (F.L.); jfmiguel{at}med.puc.cl (J.F.M.)

Apolipoprotein E (apoE) isoforms are genetic determinants of interindividual variations in lipid metabolism. To assess whether apoE is a genetic risk factor for cholesterol gallstone disease (GD), we analyzed apoE variants in populations from Chile and Germany, two countries with very high prevalence rates of this disease. ApoE genotypes were determined in Chilean gallstone patients (n = 117) and control subjects (n = 122) as well as in German gallstone patients (n = 184) and matched controls (n = 184). In addition, we studied apoE variants in subgroups of Chilean patients with strong differences in their susceptibility to acquire gallstones: 50 elderly subjects without gallstones in spite of well-known risk factors for this disease (gallstone-resistant) and 32 young individuals with gallstones but without risk factors (gallstone-susceptible). Furthermore, correlation analysis of apoE genotypes with cholesterol crystal formation times, biliary cholesterol saturation index (CSI), and gallstone cholesterol contents was performed in 81 cholecystectomized patients. In this study analyzing the largest sample set available, apoE4 genotype was not associated with an increased frequency of GD in either population. Moreover, in the Chilean population after adjusting for risk factors such as gender, age, body mass index, serum lipids, and glucose, the odds ratio for the association of the apoE4 allele and GD was significantly (P < 0.05) <1. Also, genotypes were not correlated with cholesterol crystal formation time, CSI, or gallstone cholesterol content. In contrast to previous smaller studies, apoE polymorphisms were not associated with susceptibility to cholesterol GD in high-risk populations.

Supplementary key words gallstone disease • cholesterol • genetic association study

Abbreviations: apoE, apolipoprotein E; BMI, body mass index; CSI, cholesterol saturation index; GD, gallstone disease


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Copyright © 2007 by the American Society for Biochemistry and Molecular Biology.