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Papers In Press, published online ahead of print June 1, 2004
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Department of Clinical Nutrition, Kuopio 70211
Corresponding Author: helena.gylling{at}uku.fi
The role of polymorphisms of sitosterolemia genes ABCG5 and ABCG8 in the regulation of cholesterol metabolism and insulin sensitivity were studied in mildly hypercholesterolemic non-coronary subjects (n=263, 144 men, 119 women). They were divided into tertiles by baseline serum cholestanol to cholesterol ratio (= 118.3 and =147.7 10²mmol/mol of cholesterol), a surrogate marker of cholesterol absorption efficiency. The lowest cholestanol tertile associated with the characteristics of the metabolic syndrome (p<0.01 for all): high BMI, plasma glucose, serum insulin, serum triglycerides and cholesterol synthesis markers (cholestenol, desmosterol and lathosterol), and low HDL cholesterol level and low cholesterol absorption markers (campesterol and sitosterol). The 19 H allele of the ABCG8 gene accumulated in the lowest cholestanol tertile (p<0.001), and it was associated with low total and LDL cholesterol level and absorption markers, and with high synthesis markers (p<0.05 for all) suggesting low cholesterol absorption efficiency and high compensatory cholesterol synthesis in subjects with the D19H polymorphism. The 604E allele of the ABCG5 gene in men, but not in women, was associated with high BMI, plasma insulin, low serum sitosterol and high serum cholestenol levels (p<0.05 for all). In a subgroup of 71 men the 604E allele associated with insulin resistance measured with the hyperinsulinemic euglycemic clamp. In conclusion, low cholesterol absorption efficiency was associated with characteristics of the metabolic syndrome. Low serum cholesterol and cholesterol absorption was linked to the D19H polymorphism of the ABCG8 gene, and characteristics of the insulin resistance syndrome in men with the Q604E polymorphism of the ABCG5 gene.
Revised on May 20, 2004
Accepted on June 1, 2004
Polymorphisms in the ABCG5 and ABCG8 genes associate with cholesterol absorption and insulin sensitivity
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