S100A12 gene expression is increased in peripheral leukocytes in chronic kidney disease stage 4-5 patients with cardiovascular disease.
OBJECTIVE
S100A12 induces vascular inflammation contributing to the development of atherosclerosis. Serum S100A12 concentration is shown to be elevated in patients with chronic kidney disease (CKD), however the reason remains unclear.


METHODS
Transcriptional levels of S100A12 and RAGE (receptor for advanced glycation end products) were measured in peripheral leukocytes by quantitative real-time RT-PCR. Subjects were 40 patients with CKD stage 4-5, 20 of whom were affected with cardiovascular disease (CVD), and 20 healthy subjects. Serum concentrations of S100A12 and soluble RAGE were measured using enzyme-linked immunosorbent assay.


RESULTS
The serum concentration of S100A12 was significantly higher in CKD patients than in healthy subjects (78.5 ± 70.5 vs. 23.7 ± 19.2 ng/ml, p = 0.0035), but that of soluble RAGE was not. The relative quantity of S100A12 mRNA was significantly greater in leukocytes from CKD patients than in those from healthy subjects [mean (95% confidence interval of the mean): 3.1 (2.2-3.9) vs. 1.2 (0.8-1.7), p = 0.0001], however that of RAGE mRNA was not. The serum concentration of S100A12 was significantly correlated with the relative quantity of S100A12 mRNA among uremic CKD patients (r(2) = 0.656, p < 0.0001). Both the serum concentration and gene expression of S100A12 were significantly higher in patients who had CVD than in those who did not.


CONCLUSIONS
Excessive expression of the S100A12 gene in uremic leukocytes is relevant to its increased serum concentration, particularly in those affected with CVD.
Division of Nephrology, Department of Internal Medicine, Tokyo Metropolitan Komagome General Hospital, Tokyo, Japan.
Masaki
M
Hara
Minoru
M
Ando
Taku
T
Morito
Hirohiko
H
Nokiba
Yuko
Y
Iwasa
Ken
K
Tsuchiya
Kosaku
K
Nitta
D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood*; D003430:Cross-Sectional Studies; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood / Q000235:genetics; D051436:Renal Insufficiency, Chronic / Q000097:blood*; D009418:S100 Proteins / Q000097:blood / Q000235:genetics*; D000067616:S100A12 Protein
D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human