Cholesterol concentration in plasma depends on the amount of

Cholesterol concentration in plasma depends on the amount of cholesterol from the diet and its intestinal absorption, on de novo synthesis, and on its biliary excretion [10]. Previous studies have reported increased intestinal cholesterol INDY in non-FH ADH subjects that may partially explain plasma hypercholesterolemia in these subjects [11], [12]. However, no familial cosegregation studies have been performed to study the linkage between hyper-absorption and high LDL cholesterol in non-FH ADH families. Normal serum contains small but detectable amounts of non-cholesterol sterols, including plant sterols, also named phytosterols, and cholestanol, and their ratios to cholesterol are accepted surrogate markers for the efficiency of cholesterol intestinal absorption [13], [14]. Efficiency of cholesterol intestinal absorption is a partly inherited phenomenon. Heredity of cholesterol absorption has been demonstrated in siblings of hypercholesterolemic probands with low and high serum cholestanol to cholesterol ratio [15].
Materials and methods
Results The main clinical and biochemical characteristics of the 54 non-FH ADH probands are presented in Table 1. Probands were mostly healthy women (65%) with high total cholesterol and LDL cholesterol and normal triglycerides as expected due to inclusion and exclusion criteria. The concentration of the non-cholesterol sterols is represented by ratio to total cholesterol determined by HPLC-MS/MS. Ten non-FH ADH probands fulfilled the diagnostic criteria of hyperabsorbers. Table 2 shows the main lipid characteristics of these subjects and of 10 non-hyperabsorber probands used for comparison. There were differences between groups in body mass index, waist circumference and triglycerides. Other clinical variables, including dietary characteristics, did not differ between hyperabsorber and non-hyperabsorber probands. Mean values of cholestanol, sitosterol, campesterol and stigmasterol showed statistically significant (P = 0.003 for cholestanol and P < 0.001 for phytosterols) between both groups. Table 3 shows the clinical and biochemical characteristics of the family members in both, hyperabsorber and non-hyperabsorber families. In families with a hyperabsorber proband, there were significant differences between affected and non-affected subjects for total cholesterol, LDL cholesterol, non-HDL cholesterol and apolipoprotein B, without differences in BMI. Intestinal cholesterol absorption markers were higher in affected subjects, with significant differences for cholestanol. In non-hyperabsorber families, there were similar lipid differences than in hyperabsorber families and affected subjects had higher BMI than non-affected subjects. The concentration of cholesterol absorption markers was not significantly different in the non-hyperabsorber families, except for cholestanol. No difference was found in desmosterol between affected and non-affected subjects in hyperabsorber families and significant difference was found between affected and non-affected subjects in non-hyperabsorber families (P = 0.004), probably associated with a significantly higher BMI. Desmosterol, was significantly lower in affected subjects from hyperabsorber families than in affected subjects from non-hyperabsorber families (2.76 (2.26–2.94) vs. 2.96 (2.67–3.32), P = 0.035). An opposite pattern although without reaching statistical significance was found for intestinal cholesterol absorption markers (6.87 (5.43–8.75) vs. 5.90 (4.90–6.77), P = 0.083).