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

Juan G. Mella, Ramin Schirin-Sokhan, Attilio Rigotti, Fernando Pimentel, Luis Villarroel, Hermann E. Wasmuth, Tilman Sauerbruch, Flavio Nervi, Frank Lammert, and Juan Francisco Miquel

Gastroenterology, Pontificia Universidad Catolica de Chile, Santiago, Santiago 6513677

Corresponding Author: jfmiquel{at}med.puc.cl

Background & Aims: Apolipoprotein E (ApoE) isoforms are genetic determinants of interindividual variations in lipid metabolism. To assess if ApoE is a genetic risk factor for cholesterol gallstone disease, we analyzed ApoE variants in populations from Chile and Germany, two countries with very high prevalence rates of this disease. Methods: ApoE genotypes were determined in Chilean gallstone (n = 117) and control subjects (n = 122) as well as 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. Results: In this study analyzing the largest sample set available ApoE 4 genotype was not associated with an increased frequency of gallstone disease in either population. Moreover, in the Chilean population after adjusting for risk factors like gender, age body mass index, serum lipids and glucose, the odds ratio (OR) for the association of ApoE4 allele and gallstone disease was even significantly (p < 0.05) lower than 1. Also, genotypes were not correlated with cholesterol crystal formation time, CSI, or gallstone cholesterol content. Conclusion: In contrast to previous smaller studies, ApoE polymorphisms are not associated with susceptibility to cholesterol gallstone disease in high-risk populations.

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?