Polymorphisms in the ABCG5 and ABCG8 genes associate with cholesterol absorption and insulin sensitivity.
The roles of polymorphisms of the sitosterolemia genes ABCG5 and ABCG8 in the regulation of cholesterol metabolism and insulin sensitivity were studied in mildly hypercholesterolemic noncoronary subjects (n = 263, 144 men and 119 women) divided into tertiles by baseline serum cholestanol-to-cholesterol ratio (< or = 118.3 and > or = 147.7 10(2) x mmol/mol cholesterol), a surrogate marker of cholesterol absorption efficiency. The lowest cholestanol tertile was associated with high body mass index (BMI), plasma glucose, serum insulin and triglycerides, and cholesterol synthesis markers (cholestenol, desmosterol, lathosterol) and low HDL cholesterol and cholesterol absorption markers (campesterol, sitosterol) (P < 0.01 for all). The 19H allele of the ABCG8 gene accumulated in the lowest cholestanol tertile (P < 0.001) and was associated with low total and LDL cholesterol and absorption markers and with high synthesis markers (P < 0.05 for all). The 604E allele of the ABCG5 gene in men 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 was 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 were linked to the D19H polymorphism of the ABCG8 gene, and characteristics of the insulin resistance syndrome in men were linked with the Q604E polymorphism of the ABCG5 gene.
Gylling
Helena
H
Department of Clinical Nutrition, University of Kuopio, Kuopio University Hospital, Kuopio, Finland. helena.gylling@uku.fi
Hallikainen
Maarit
M
Pihlajamäki
Jussi
J
Agren
Jyrki
J
Laakso
Markku
M
Rajaratnam
Radhakrishnan A
RA
Rauramaa
Rainer
R
Miettinen
Tatu A
TA
D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000042:Absorption; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics; D008074:Lipoproteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
C416945:ABCG5 protein, human; C416946:ABCG8 protein, human; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D001786:Blood Glucose; D008074:Lipoproteins; D002784:Cholesterol