Impaired cholesterol metabolism appears to be the primary factor [2] in the formation of cholesterol gallstones and polyps in the gallbladder [12]. A prerequisite for their development is accumulation of cholesterol in the bile, causing cholesterol supersaturation. This often, but not always, reduces gallbladder motility because of excessive accumulation of cholesterol esters within epithelial macrophages of the gallbladder wall and formation of foam cells (cholesterolosis). Gallbladder dysfunction is caused by cholesterol action on sarcoleme membrane of the gallbladder smooth muscles [13]. However, some patients with cholesterolosis have a normal functioning gallbladder, as in the case of patient P. Cholesterol in bile is accumulated as micelles and vesicles under normal physiologic conditions. Supersaturated mono lamellar vesicles coalesce into multi lamellar vesicles and liposomes (liquid crystals), which transform into solid mono crystals of cholesterol [14]. Gallbladder hypomotility reduces the enterohepatic circulation and increases the aggregation of bile components. The monozygotic twin patients described here indicate a common genetic basis for their gallstone disease and cholesterolosis.

Many studies indicate that gallstone susceptibility has genetic components [5-7,15]. The genetic polymorphisms in various genes for apo E, apo B, apo A1, LDL receptor, cholesterol ester transfer and LDL receptor-associated protein, have been implicated in gallstone and polyp formation.

Kesaniemi et al. [16] have studied the relative contribution of genetic factors to biliary and serum lipid composition in 17 monozygotic and 18 dizygotic middle-aged pairs of twins. Their data suggest that molar percentage of biliary cholesterol, bile acid composition, cholesterol synthesis, bile cholesterol saturation and gallstone formation may be under significant genetic control.

Determination of zygosity may be done by comparison of physical characteristics, blood group or tissue typing, chromosome studies, or examination of various other polymorphic protein markers. However, all these markers may not be uniformly informative. Here, we used a multi locus DNA fingerprinting method for determining the twin zygosity of our patients. This method uses microsatellite or minisatellite core probes [11], requires only a small amount of DNA, and detects the restriction fragment length polymorphisms (RFLP) which are a result of allelic differences in the loci that contain the core sequences. The DNA fingerprinting analysis revealed that patients F. and P. were indeed monozygotic twins. Both had a predominance of minor dense particles of LDL, but different forms of cholesterol accumulation (gallstone disease in one and cholesterolosis in the other). Patient F. showed marked hypotonya of gallbladder and hypertonya of sphincter of Oddi. But in patient P., we observe the normal function of the gallbladder and sphincter Oddi. We conclude that heterogeneity of the LDL fraction in patient F. resulted in aggregation of supersaturated bile with formation of gallstones, and that the normal gallbladder function in patient P. led to passive and active cholesterol absorption.

At present, it is unclear why in some patients cholesterol accumulation occurs in the gallbladder wall (cholesterolosis), and in others it occurs in the gallbladder cavity (gallstone disease). We conclude that gallstone disease and cholesterolosis showing identical changes in the plasma LDL subfraction may be caused by different functional conditions within the gallbladder, which may be due to epigenetic, metabolic or environmental factors, since both diseases have a common genetic basis.