TheInterleukin-6Gene Promoter Polymorphism -174 and Atherosclerotic Events in Overweight Transplanted Patients

Chronic inflammation plays a pivotal role in atherosclerosis. We hypothesized that combining overweight and a greater genetic capacity to produce IL-6 predicted byIL-6gene promoter polymorphism at position -174 (G→C) may allow to identify individuals exhibiting higher IL-6 and C-reactive protein (CRP) concentrations with a higher risk of atherosclerotic events (AE). The occurrence of AE was analyzed with respect to body mass index,IL-6gene promoter polymorphism at position -174 (G→C), and other relevant risk factors, retrospectively, in 217 renal transplant recipients and, prospectively, in 132. Circulating IL-6 concentrations were closely related to BMI (r=0.55,P=.0005). In overweight patients, serum IL-6 concentration was found to be significantly lower in C carriers than in GG patients (4.2 [1.0–5.1] versus 7.3 pg/mL [4.4–100];P=.025). The incidence of AE was higher in overweight GG patients (29.5% versus 10.1%;P=.0003). In multivariate analysis, overweight-GG had an increased risk to develop AE (HR 2.96 [95% CI 1.09–8.04],P=.034in the retrospective cohort, and HR 2.99 [95% CI 0.92–9.33],P=.069in the prospective cohort). All these data are consistent with a role for both genetic and environmental determinants of inflammation (white adipose tissue mass) in the development of AE in renal transplanted patients.

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Independent association of an APOE gene promoter polymorphism with increased risk of myocardial infarction and decreased APOE plasma concentrations--the ECTIM Study

Human Molecular Genetics ◽

10.1093/hmg/9.1.57 ◽

2000 ◽

Vol 9 (1) ◽

pp. 57-61 ◽

Cited By ~ 99

Author(s):

J.-C. Lambert

Keyword(s):

Myocardial Infarction ◽

Plasma Concentrations ◽

Gene Promoter ◽

Promoter Polymorphism ◽

Apoe Gene ◽

Increased Risk ◽

Independent Association ◽

Gene Promoter Polymorphism

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Mycophenolate Mofetil and C-Reactive Protein in Renal Transplant Recipients

Transplantation Journal ◽

10.1097/01.tp.0000248864.21574.92 ◽

2007 ◽

Vol 83 (1) ◽

pp. 48-53 ◽

Cited By ~ 7

Author(s):

Brian M. Wong ◽

Michael Huang ◽

Jeffrey S. Zaltzman ◽

G V. Ramesh Prasad

Keyword(s):

Mycophenolate Mofetil ◽

Renal Transplant ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

C Reactive Protein ◽

Reactive Protein

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An Increase in Myeloid-Related Protein Serum Levels Precedes Acute Renal Allograft Rejection

Journal of the American Society of Nephrology ◽

10.1681/asn.v1291947 ◽

2001 ◽

Vol 12 (9) ◽

pp. 1947-1957

Author(s):

KLAUS BURKHARDT ◽

MARTIN RADESPIEL-TRÖGER ◽

HARALD D. RUPPRECHT ◽

MARGARETE GOPPELT-STRUEBE ◽

REGINE RIESS ◽

...

Keyword(s):

Pilot Study ◽

Renal Transplant ◽

Acute Rejection ◽

High Sensitivity ◽

Serum Levels ◽

Renal Transplant Recipients ◽

Related Protein ◽

Transplant Recipients ◽

C Reactive Protein ◽

Reactive Protein

Abstract. Upon interaction with activated endothelium, monocytes and neutrophils form complexes of myeloid-related protein 8 (MRP8) (S100A8) and MRP14 (S100A9), two members of the calcium-binding S100 family that are secreted during transendothelial migration. In a pilot study of 20 renal transplant recipients and a validation study of 36 renal transplant recipients, MRP8/14 serum levels were measured with an enzyme-linked immunosorbent assay for 28 d, associated with C-reactive protein and creatinine serum levels, and grouped according to biopsy-proven acute rejection. Serum levels of MRP8/14 but not C-reactive protein were significantly increased for several days during the first 2 wk for the acute rejection groups in both studies (P < 0.005, on day 6 after transplantation). As determined by using receiver operating characteristic curves, the optimal cutoff for 100% specificity and high sensitivity (67%) for acute rejection on day 6 after transplantation was calculated to be 4.2 μg/ml for MRP8/14 in the pilot study; this value was confirmed in the validation study. Positive MRP8/14 serum levels preceded acute rejection episodes by a median of 5 d. A 3-d course of intravenous methylprednisolone therapy reduced prerejection MRP8/14 serum levels from 5.7 μg/ml to 3.3 μg/ml (P < 0.05). All MRP8/14 serum levels were below the cutoff during urinary tract infections, delayed graft function, or cytomegalovirus infections, and these values did not differ significantly from control values. It is concluded that the MRP8/14 complex is a very early serum marker suitable for monitoring of acute rejection with high sensitivity and specificity.

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