Leukocyte ABCA1 gene expression is associated with fasting glucose concentration in normoglycemic men.
Adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) mediates the efflux of cholesterol to apolipoprotein A1, a process necessary for high-density lipoprotein (HDL) formation and reverse cholesterol transport. In patients with Tangier disease, mutations in ABCA1 result in low circulating HDL-cholesterol and predisposition to coronary heart disease (CHD). ABCA1 gene expression is decreased in diabetic mice. In humans, glycated hemoglobin (HbA(1c)) predicted future CHD events, even within the normal range. We hypothesised that leukocyte ABCA1 gene expression would be inversely associated with indices of glycemia in normoglycemic men. Fasting blood samples were taken from 32 healthy, nonsmoking, normoglycemic men (age 23 to 46 years). ABCA1, peroxisome proliferator-activated receptor gamma (PPARgamma), and liver X receptor alpha (LXRalpha) gene expressions in circulating leukocytes were measured using TaqMan technology. Significant inverse associations between ABCA1 gene expression and both fasting glucose concentration (r = -0.49, P =.008) and age (r = -0.39, P =.043) were found. There was no association with HbA(1c) (r = -0.23, P =.238) or HDL-cholesterol concentration (r = 0.02, P =.904). In a multiple regression model, fasting glucose remained a significant independent predictor (P =.037), whereas age did not (P =.226). Mechanisms underlying the association were explored; there were no significant associations between fasting glucose concentration and leukocyte PPARgamma gene expression, or between fasting glucose concentration and leukocyte LXRalpha gene expression. This is the first demonstration of an association between ABCA1 gene expression and fasting glucose concentration in vivo.
Albrecht
C
C
Medical Research Council Clinical Sciences Center, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, UK.
Simon-Vermot
I
I
Elliott
J I
JI
Higgins
C F
CF
Johnston
D G
DG
Valabhji
J
J
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000097:blood / Q000235:genetics*; D000328:Adult; D000375:Aging; D001786:Blood Glucose / Q000032:analysis*; D008076:Cholesterol, HDL / Q000097:blood; D004268:DNA-Binding Proteins; D005215:Fasting; D015870:Gene Expression; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D016014:Linear Models; D008099:Liver / Q000737:chemistry; D000071518:Liver X Receptors; D008297:Male; D008875:Middle Aged; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D001786:Blood Glucose; D008076:Cholesterol, HDL; D004268:DNA-Binding Proteins; D006442:Glycated Hemoglobin; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C577836:ABCA1 protein, human; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse