Dataset Information

Sequence variants of peroxisome proliferator-activated receptor-gamma gene and the clinical courses of patients with end-stage renal disease.

ABSTRACT:

Background

PPAR-γ single nucleotide polymorphisms (SNPs) reportedly play an important role in determining metabolic risk among diverse population. Whether PPAR-γ SNPs affect the clinical courses in ESRD patients is unknown.

Methods

From a multicenter cohort, we identified 698 patients with prevalent ESRD between 2002 and 2003, and other 782 healthy subjects as control. Two PPAR-γ SNPs, Pro12Ala (rs1801282) and C161T (rs3856806), were genotyped and their association with ESRD was examined. Both groups were prospectively followed until 2007, and the predictability of genotypes for the long-term survival of ESRD patients was analyzed.

Results

After multivariable-adjusted regression, GG genotype of Pro12Ala was significantly more likely to associate with ESRD (P < 0.001) among patients with non-diabetes-related ESRD. Cox's proportional hazard regression showed that both Pro12Ala and C161T polymorphisms were significant predictors of mortality in ESRD patients with DM (Pro12Ala: GG versus other genotypes, hazard ratio [HR] <0.01; P < 0.001; for C161T, CC versus TT genotypes, HR 2.86; P < 0.001; CT versus TT genotypes, HR 1.93; P < 0.001).

Conclusion

This is the first and largest study to evaluate PPAR-γ SNPs in ESRD patients. Further mechanistic study is needed to elucidate the role of PPAR-γ among ESRD patients.

SUBMITTER: Chao CT

PROVIDER: S-EPMC4345048 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Sequence variants of peroxisome proliferator-activated receptor-gamma gene and the clinical courses of patients with end-stage renal disease.

Chao Chia-Ter CT Chen Yen-Ching YC Chiang Chih-Kang CK Huang Jenq-Wen JW Hu Fu-Chang FC Fang Cheng-Chung CC Chang Chen-Chih CC Yen Chung-Jen CJ

Disease markers 20150215

<h4>Background</h4>PPAR-γ single nucleotide polymorphisms (SNPs) reportedly play an important role in determining metabolic risk among diverse population. Whether PPAR-γ SNPs affect the clinical courses in ESRD patients is unknown.<h4>Methods</h4>From a multicenter cohort, we identified 698 patients with prevalent ESRD between 2002 and 2003, and other 782 healthy subjects as control. Two PPAR-γ SNPs, Pro12Ala (rs1801282) and C161T (rs3856806), were genotyped and their association with ESRD was e ...[more]

PMID: 25784779

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Project description:Peroxisome proliferator activated receptor-gamma (PPAR-gamma) is abundantly expressed in atherosclerotic lesions and is implicated in atherogenesis. The existence of three splice variants, PPAR-gamma 1, PPAR-gamma 2, and PPAR-gamma 3 has been established. Using monocyte-derived macrophages from cynomolgus monkeys, we demonstrate here the identification of two new PPAR-gamma exons, exon C and exon D, which splice together with already established exons A1, A2, and B in the 5(') terminal region to generate four novel PPAR-gamma subtypes, PPAR-gamma 4, -gamma 5, -gamma 6, and -gamma 7. PPAR-gamma 4 and gamma 5 were detected only in macrophages whereas gamma 6 and gamma 7 were expressed both in macrophages and adipose tissues. None of these novel isoforms were detected in muscle, kidney, and spleen from monkeys. We found sequences identical to exons C and D in the human genome database. These and all PPAR-gamma exons known to date are encoded by a single gene, located from region 10498 K to 10384 K on human chromosome 3. We cloned and expressed PPAR-gamma 1, PPAR-gamma 4, and PPAR-gamma 5 proteins in yeast using the expression vector pPICZB. As expected, all recombinant proteins showed a molecular weight of approximately 50 kDa. We also investigated the effect of a high-fat diet on the level of macrophage PPAR-gamma expression in monkeys. RT-PCR showed a significant increase in total PPAR-gamma and ABCA1 mRNA levels in macrophages of fat-fed monkeys (n=7) compared to those maintained on a normal diet (n=2). However, none of the novel isoforms seemed to be induced by fat-feeding. We used tetracycline-responsive expression vectors to obtain moderate expression of PPAR-gamma 4 and -gamma 5 in CHO cells. In these cells, expression of PPAR-gamma 5 but not -gamma 4 repressed the expression of ABCA1. Neither isoform modulated the expression of lipoprotein lipase. Our results suggest that individual PPAR-gamma isoforms may be responsible for unique tissue-specific biological effects and that PPAR-gamma 4 and -gamma 5 may modulate macrophage function and atherogenesis.

Dataset Information

Sequence variants of peroxisome proliferator-activated receptor-gamma gene and the clinical courses of patients with end-stage renal disease.

Background

Methods

Results

Conclusion

Publications

Sequence variants of peroxisome proliferator-activated receptor-gamma gene and the clinical courses of patients with end-stage renal disease.

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