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Peroxisome proliferator-activated receptor gamma polymorphisms affect systemic inflammation and survival in end-stage renal disease patients starting renal replacement therapy.

Abstract：

BACKGROUND:Inflammation may contribute to the markedly increased cardiovascular morbidity and mortality in end-stage renal disease (ESRD). However, the prevalence of inflammation varies in different ESRD populations. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is an important nuclear signaling protein that may regulate inflammatory response, and recent studies have revealed genetic polymorphisms that have significant effect on PPAR-gamma signaling. The aim of this study was to clarify whether the PPAR-gamma 161C/T and PPAR-gamma2 Pro12Ala single-nucleotide polymorphisms (SNPs) influence the inter-individual variance of inflammation and mortality in ESRD patients. METHODS:The present prospective study included 229 incident Caucasian ESRD patients (62% males) just prior to starting renal replacement therapy and 207 healthy controls (62% males). Blood samples were taken for measuring systemic inflammatory (CRP, TNF-alpha, IL-6) and nutritional (S-albumin) parameters. The presence of diabetes mellitus, malnutrition (subjective global assessment (SGA)) and cardiovascular disease (CVD) were also assessed. Genotyping of the two PPAR-gamma SNPs was performed using Pyrosequencing. During follow-up (1621+/-63 days), both all-cause and CVD-mortality were investigated. RESULTS:ESRD patients had a higher prevalence of both the PPAR-gamma 161 CC and PPAR-gamma2 Pro12Pro genotypes than the general population (p<0.01). Whereas the Pro12Pro genotype was associated with higher median serum levels of both hs-CRP (p<0.05) and TNF-alpha (p<0.01) the 161CC genotype was associated with a significantly higher (6.6 mg/L versus 3.3 mg/L; p<0.01) median hs-CRP level. Following adjustment for age, gender, SGA and CVD a significantly higher mortality rate was observed in patients with the Pro12Pro genotype. CONCLUSION:This study demonstrates significant differences in PPAR-gamma genotype distribution between ESRD patients and healthy controls. Furthermore, as the PPAR-gamma2 Pro12Pro genotype was associated with both higher levels of biomarkers of inflammation as well as shorter survival, genetic polymorphisms seem to play a role in determining systemic inflammatory status and outcome in this patient group.

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

Yao Q,Nordfors L,Axelsson J,Heimbürger O,Qureshi AR,Báràny P,Lindholm B,Lönnqvist F,Schalling M,Stenvinkel P

doi

10.1016/j.atherosclerosis.2005.01.033

keywords:

subject

Has Abstract

pub_date

2005-09-01 00:00:00

pages

105-11

issue

eissn

0021-9150

issn

1879-1484

pii

S0021-9150(05)00108-5

journal_volume

182

pub_type

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Peroxisome proliferator-activated receptor gamma polymorphisms affect systemic inflammation and survival in end-stage renal disease patients starting renal replacement therapy.