POLYMORPHISMS AT THE APO-B, APOA-I, AND CHOLESTERYL ESTER TRANSFER PROTEIN GENE LOCI IN PATIENTS WITH GALLBLADDER-DISEASE

Alterations in lipoprotein levels are reported to be related to an inc reased risk of gallstones. Plasma lipid metabolism is regulated by a n umber of proteins that are polymorphic in the population. The present research was designed to investigate the association between the polym orphisms of these proteins and the presence of various gallbladder dis eases. Restriction fragment length polymorphisms (RFLPs) of apolipopro tein B (XbaI, EcoRI), apolipoprotein A-I (PstI, MspI), and cholesteryl ester transfer protein (CETP) (EcoNI, TaqIA, TaqIB) genes were examin ed in a series of 210 cholecystectomy patients operated on for symptom atic gallbladder disease and in 92 healthy controls. The patients were categorized into four groups according to the type of gallstones and the presence or absence of cholesterolosis. The distribution of CETP T aqIB polymorphism in the patients with cholesterol gallstones differed significantly from that in the controls, with the B1B1 jects (39.7%) (P = 0.036). The patients with both cholesterol and non-cholesterol st ones had lower high density lipoprotein (HDL)-cholesterol levels than the control subjects. However, the most distinct difference was found in the gallstone patients with the B2B2 genotype (P = 0.006). The freq uency of the X1X1 genotype of the apolipoprotein B XbaI polymorphism w as markedly higher in the patients with acalculous cholesterolosis (48 .9%) or cholesterolosis with stones (58.1%) than in the gallstone pati ents with cholesterol stones (27.2%) or with non-cholesterol stones (3 4.1%) (P = 0.002). The present data suggest that CETP gene polymorphis m may be associated with cholesterol gallstone disease, probably in co mbination with some additional factor that reduces the plasma HDL chol esterol concentration, especially in TaqIB B2B2 genotype. Changes in t he apolipoprotein B structure possibly associated with the XbaI polymo rphism may be involved in the accumulation of neutral lipids during th e development of cholesterolosis of the gallbladder.