Determinants of leukocyte adenosine triphosphate-binding cassette transporter G1 gene expression in type 2 diabetes mellitus.
Cellular cholesterol efflux is regulated by cholesterol transporters including adenosine triphosphate-binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor class B type I (SR-BI). We have investigated whether the expression of these transporters is affected by type 2 diabetes mellitus and the association with glycemic indexes and oxidized low-density lipoprotein (oxLDL). Messenger RNA of ABCA1, ABCG1, and SR-BI in peripheral monocytes was measured in 30 diabetic patients and 30 matched controls. Plasma oxLDL and advanced glycation end products (AGEs) were assayed by enzyme-linked immunosorbent assay. Cellular cholesterol efflux from monocytes to serum was determined in a subgroup chosen randomly. The expression of ABCG1 was decreased in diabetic patients (P < .05), whereas the levels of ABCA1 and SR-BI were comparable between the 2 groups. Fasting glucose, hemoglobin A(1c), AGEs, and oxLDL were all significantly increased in diabetic patients. There was an inverse correlation between serum AGEs and ABCG1 (r = -0.44, P < .05) that remained significant after adjusting for potential confounding factors. No associations between fasting glucose, hemoglobin A(1c), plasma lipids, or oxLDL and the expression of ABCG1, ABCA1, or SR-BI were found. Cholesterol efflux from monocytes to standard serum or autologous serum was significantly impaired in diabetic patients, and the reduction in efflux to autologous serum correlated with the expression of ABCG1 (r = 0.60, P < .05). The expression of ABCG1 in monocytes is reduced in type 2 diabetes mellitus and is partly related to serum AGEs concentration. The reduction in ABCG1 is associated with impairment in cholesterol efflux and may contribute to accelerated foam cell formation in diabetic patients.
Zhou
Huali
H
Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong.
Tan
Kathryn C B
KC
Shiu
Sammy W M
SW
Wong
Ying
Y
D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D006442:Glycated Hemoglobin / Q000032:analysis; D017127:Glycation End Products, Advanced / Q000097:blood; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051122:Scavenger Receptors, Class B / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism
D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D001786:Blood Glucose; D002784:Cholesterol; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D051122:Scavenger Receptors, Class B; D014280:Triglycerides; C577836:ABCA1 protein, human; C419353:ABCG1 protein, human; C495124:SCARB1 protein, human; C099252:oxidized low density lipoprotein