Skip to main content
Top
Published in: Diagnostic Pathology 1/2013

Open Access 01-12-2013 | Research

The association between the PPARγ2 Pro12Ala polymorphism and nephropathy susceptibility in type 2 diabetes: a meta-analysis based on 9,176 subjects

Authors: Lei Wang, Zan Teng, Shuang Cai, Difei Wang, Xin Zhao, Kai Yu

Published in: Diagnostic Pathology | Issue 1/2013

Login to get access

Abstract

Background

The polymorphism Pro12Ala in peroxisome proliferator-activated receptor­γ2 gene (PPARγ2) has been reported to be associated with diabetic nephropathy (DN) in some studies, though the results remain inconclusive. To explore this relationship between PPARγ2 Pro12Ala polymorphism and the susceptibility for DN, a cumulative meta-analysis was performed in this study.

Method

PubMed, Medline, Embase and Web of Science databases have been systematically searched to identify relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.

Results

18 studies were included in this meta-analysis, involving 3,361 cases and 5,815 controls. The PPARγ2 Ala12 allele was significantly associated with decreased risk of DN based on dominant model (OR=0.778; 95%CI=0.618–0.981; Pheterogeneity=0.008; P=0.034). In the stratified analysis by ethnicity, significantly decreased risks were found among Caucasians for dominant model (OR=0.674; 95%CI=0.500–0.909; Pheterogeneity=0.079; P=0.010), while there was no significant association was found in Asians.

Conclusions

The results from the present meta-analysis indicated that the Pro12Ala polymorphism in PPARγ2 gene is not a risk factor for DN in type 2 diabetes (T2D). Further large and well-designed studies are needed to confirm this conclusion.

Virtual slides

Appendix
Available only for authorised users
Literature
1.
go back to reference Ayodele OE, Alebiosu CO, Salako BL: Diabetic nephropathy: A review of the natural history, burden, risk factors and treatment. J Natl Med Assoc. 2004, 96: 1445-1454.PubMedCentralPubMed Ayodele OE, Alebiosu CO, Salako BL: Diabetic nephropathy: A review of the natural history, burden, risk factors and treatment. J Natl Med Assoc. 2004, 96: 1445-1454.PubMedCentralPubMed
2.
go back to reference Moczulski DK, Rogus JJ, Antonellis A, Warram JH, Krolewski AS: Major susceptibility locus for nephropathy in type 1 diabetes on chromosome 3q: Results of novel discordant sib-pair analysis. Diabetes. 1998, 47: 1164-1169. 10.2337/diabetes.47.7.1164.CrossRefPubMed Moczulski DK, Rogus JJ, Antonellis A, Warram JH, Krolewski AS: Major susceptibility locus for nephropathy in type 1 diabetes on chromosome 3q: Results of novel discordant sib-pair analysis. Diabetes. 1998, 47: 1164-1169. 10.2337/diabetes.47.7.1164.CrossRefPubMed
3.
go back to reference Guan Y, Zhang Y, Schneider A, Davis L, Breyer RM, Breyer MD: Peroxisome proliferator-activated receptor-gamma activity is associated with renal microvasculature. Am J Physiol Renal Physiol. 2001, 281: F1036-F1046.CrossRefPubMed Guan Y, Zhang Y, Schneider A, Davis L, Breyer RM, Breyer MD: Peroxisome proliferator-activated receptor-gamma activity is associated with renal microvasculature. Am J Physiol Renal Physiol. 2001, 281: F1036-F1046.CrossRefPubMed
4.
go back to reference Deeb SS, Fajas L, Nemoto M, et al.: A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet. 1998, 20: 284-287. 10.1038/3099.CrossRefPubMed Deeb SS, Fajas L, Nemoto M, et al.: A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet. 1998, 20: 284-287. 10.1038/3099.CrossRefPubMed
5.
go back to reference Liu L, Zheng T, Wang F, et al.: Pro12Ala polymorphism in the PPARG gene contributes to the development of diabetic nephropathy in Chinese type 2 diabetic patients. DiabetesCare. 2010, 33: 144-149. 10.2337/dc09-1258. Liu L, Zheng T, Wang F, et al.: Pro12Ala polymorphism in the PPARG gene contributes to the development of diabetic nephropathy in Chinese type 2 diabetic patients. DiabetesCare. 2010, 33: 144-149. 10.2337/dc09-1258.
6.
go back to reference Argmann CA, Cock TA, Auwerx J: Peroxisome proliferator-activated receptor gamma: The more the merrier?. Eur J Clin Invest. 2005, 35: 82-92. 10.1111/j.1365-2362.2005.01456.x.CrossRefPubMed Argmann CA, Cock TA, Auwerx J: Peroxisome proliferator-activated receptor gamma: The more the merrier?. Eur J Clin Invest. 2005, 35: 82-92. 10.1111/j.1365-2362.2005.01456.x.CrossRefPubMed
7.
go back to reference Desvergne B, Michalik L, Wahli W: Be fit or be sick: Peroxisome proliferator-activated receptors are down the road. Mol Endocrinol. 2004, 18: 1321-1332. 10.1210/me.2004-0088.CrossRefPubMed Desvergne B, Michalik L, Wahli W: Be fit or be sick: Peroxisome proliferator-activated receptors are down the road. Mol Endocrinol. 2004, 18: 1321-1332. 10.1210/me.2004-0088.CrossRefPubMed
8.
go back to reference Caramori ML, Canani LH, Costa LA, Gross JL: The human peroxisome proliferator-activated receptor gamma2 (PPAR-gamma2) Pro12Ala polymorphism is associated with decreased risk of diabetic nephropathy in patients with type 2 diabetes. Diabetes. 2003, 52: 3010-3013. 10.2337/diabetes.52.12.3010.CrossRefPubMed Caramori ML, Canani LH, Costa LA, Gross JL: The human peroxisome proliferator-activated receptor gamma2 (PPAR-gamma2) Pro12Ala polymorphism is associated with decreased risk of diabetic nephropathy in patients with type 2 diabetes. Diabetes. 2003, 52: 3010-3013. 10.2337/diabetes.52.12.3010.CrossRefPubMed
9.
go back to reference Herrmann SM, Ringel J, Wang JG, Staessen JA, Brand E: Peroxisome proliferator-activated receptor-gamma2 polymorphism Pro12Ala is associated with nephropathy in type 2 diabetes: The Berlin Diabetes Mellitus (BeDiaM) Study. Diabetes. 2002, 51: 2653-2657. 10.2337/diabetes.51.8.2653.CrossRefPubMed Herrmann SM, Ringel J, Wang JG, Staessen JA, Brand E: Peroxisome proliferator-activated receptor-gamma2 polymorphism Pro12Ala is associated with nephropathy in type 2 diabetes: The Berlin Diabetes Mellitus (BeDiaM) Study. Diabetes. 2002, 51: 2653-2657. 10.2337/diabetes.51.8.2653.CrossRefPubMed
10.
go back to reference Masugi J, Tamori Y, Mori H, Koike T, Kasuga M: Inhibitory effect of a proline-to-alanine substitution at codon 12 of peroxisome proliferator-activated receptor-gamma 2 on thiazolidinedione-induced adipogenesis. Biochem Biophys Res Commun. 2000, 268: 178-182. 10.1006/bbrc.2000.2096.CrossRefPubMed Masugi J, Tamori Y, Mori H, Koike T, Kasuga M: Inhibitory effect of a proline-to-alanine substitution at codon 12 of peroxisome proliferator-activated receptor-gamma 2 on thiazolidinedione-induced adipogenesis. Biochem Biophys Res Commun. 2000, 268: 178-182. 10.1006/bbrc.2000.2096.CrossRefPubMed
11.
go back to reference Davey SG, Egger M: Meta-analyses of randomized controlled trials. Lancet. 1997, 350: 1182- Davey SG, Egger M: Meta-analyses of randomized controlled trials. Lancet. 1997, 350: 1182-
12.
go back to reference Ioannidis JP, Boffetta P, Little J, et al.: Assessment of cumulative evidence on genetic associations: interim guidelines. Int J Epidemiol. 2008, 37: 120-132. 10.1093/ije/dym159.CrossRefPubMed Ioannidis JP, Boffetta P, Little J, et al.: Assessment of cumulative evidence on genetic associations: interim guidelines. Int J Epidemiol. 2008, 37: 120-132. 10.1093/ije/dym159.CrossRefPubMed
13.
go back to reference Mantel N, Haenszel W: Statistical aspects of the analysis of data from retrospective studies of disease. Natl Cancer Inst. 1959, 22: 719-778. Mantel N, Haenszel W: Statistical aspects of the analysis of data from retrospective studies of disease. Natl Cancer Inst. 1959, 22: 719-778.
14.
go back to reference DerSimonian R, Laird N: Meta-analysis in clinical trials. Control Clin Trials. 1986, 7: 177-188. 10.1016/0197-2456(86)90046-2.CrossRefPubMed DerSimonian R, Laird N: Meta-analysis in clinical trials. Control Clin Trials. 1986, 7: 177-188. 10.1016/0197-2456(86)90046-2.CrossRefPubMed
15.
go back to reference Begg CB, Mazumdar M: Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994, 50: 1088-1101. 10.2307/2533446.CrossRefPubMed Begg CB, Mazumdar M: Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994, 50: 1088-1101. 10.2307/2533446.CrossRefPubMed
16.
go back to reference Egger M, Smith DG, Schneider M, Minder C: Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997, 315: 629-634. 10.1136/bmj.315.7109.629.PubMedCentralCrossRefPubMed Egger M, Smith DG, Schneider M, Minder C: Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997, 315: 629-634. 10.1136/bmj.315.7109.629.PubMedCentralCrossRefPubMed
17.
go back to reference Mori H, Ikegami H, Kawaguchi Y, et al.: The Pro12→Ala substitution in PPAR-gamma is associated with resistance to development of diabetes in the general population: possible involvement in impairment of insulin secretion in individuals with type 2 diabetes. Diabetes. 2001, 50: 891-894. 10.2337/diabetes.50.4.891.CrossRefPubMed Mori H, Ikegami H, Kawaguchi Y, et al.: The Pro12→Ala substitution in PPAR-gamma is associated with resistance to development of diabetes in the general population: possible involvement in impairment of insulin secretion in individuals with type 2 diabetes. Diabetes. 2001, 50: 891-894. 10.2337/diabetes.50.4.891.CrossRefPubMed
18.
go back to reference Wu S: Study on the Relationship of Polymorphism of PPAR-g2 and Type 2 Diabetes and Diabetic Nephropathy. 2004, Tianjin: Tianjin Medical University Wu S: Study on the Relationship of Polymorphism of PPAR-g2 and Type 2 Diabetes and Diabetic Nephropathy. 2004, Tianjin: Tianjin Medical University
19.
go back to reference Maeda A, Gohda T, Funabiki K, Horikoshi S, Tomino Y: Peroxisome proliferator-activated receptor gamma gene polymorphism is associated with serum triglyceride levels and body mass index in Japanese type 2 diabetic patients. J Clin Lab Anal. 2004, 18: 317-321. 10.1002/jcla.20045.CrossRefPubMed Maeda A, Gohda T, Funabiki K, Horikoshi S, Tomino Y: Peroxisome proliferator-activated receptor gamma gene polymorphism is associated with serum triglyceride levels and body mass index in Japanese type 2 diabetic patients. J Clin Lab Anal. 2004, 18: 317-321. 10.1002/jcla.20045.CrossRefPubMed
20.
go back to reference Pollex RL, Mamakeesick M, Zinman B, Harris SB, Hegele RA, Hanley AJ: Peroxisome proliferator-activated receptor gamma polymorphism Pro12Ala is associated with nephropathy in type 2 diabetes. J Diabetes Complications. 2007, 21: 166-171. 10.1016/j.jdiacomp.2006.02.006.CrossRefPubMed Pollex RL, Mamakeesick M, Zinman B, Harris SB, Hegele RA, Hanley AJ: Peroxisome proliferator-activated receptor gamma polymorphism Pro12Ala is associated with nephropathy in type 2 diabetes. J Diabetes Complications. 2007, 21: 166-171. 10.1016/j.jdiacomp.2006.02.006.CrossRefPubMed
21.
go back to reference Erdogan M, Karadeniz M, Eroglu Z, Tezcanli B, Selvi N, Yilmaz C: The relationship of the peroxisome proliferator-activated receptor-gamma 2 exon 2 and exon 6 gene polymorphism in Turkish type 2 diabetic patients with and without nephropathy. Diabetes Res Clin Pract. 2007, 78: 355-359. 10.1016/j.diabres.2007.06.005.CrossRefPubMed Erdogan M, Karadeniz M, Eroglu Z, Tezcanli B, Selvi N, Yilmaz C: The relationship of the peroxisome proliferator-activated receptor-gamma 2 exon 2 and exon 6 gene polymorphism in Turkish type 2 diabetic patients with and without nephropathy. Diabetes Res Clin Pract. 2007, 78: 355-359. 10.1016/j.diabres.2007.06.005.CrossRefPubMed
22.
go back to reference Wei F, Wang J, Wang C, Huo X, Xue Y, Bai L: The relationship between the pro12Ala polymorphism in PPAR-g2 gene and diabetic nephropathy in Baotou. Chinese J Diabetes. 2008, 16: 679-680. Wei F, Wang J, Wang C, Huo X, Xue Y, Bai L: The relationship between the pro12Ala polymorphism in PPAR-g2 gene and diabetic nephropathy in Baotou. Chinese J Diabetes. 2008, 16: 679-680.
23.
go back to reference Li L, Liu L, Zheng T, Wang N, Wang F: Peroxisome proliferator activated receptor g2 gene P12A polymorphism and type 2 diabetic nephropathy in Han population in Shanghai. J Shanghai Jiaotong Univ. 2008, 28: 376-379. Li L, Liu L, Zheng T, Wang N, Wang F: Peroxisome proliferator activated receptor g2 gene P12A polymorphism and type 2 diabetic nephropathy in Han population in Shanghai. J Shanghai Jiaotong Univ. 2008, 28: 376-379.
24.
go back to reference Wu LS, Hsieh CH, Pei D, Hung YJ, Kuo SW, Lin E: Association and interaction analyses of genetic variants in ADIPOQ, ENPP1, GHSR, PPARgamma and TCF7L2 genes for diabetic nephropathy in a Taiwanese population with type 2 diabetes. Nephrol Dial Transplant. 2009, 24: 3360-3366. 10.1093/ndt/gfp271.CrossRefPubMed Wu LS, Hsieh CH, Pei D, Hung YJ, Kuo SW, Lin E: Association and interaction analyses of genetic variants in ADIPOQ, ENPP1, GHSR, PPARgamma and TCF7L2 genes for diabetic nephropathy in a Taiwanese population with type 2 diabetes. Nephrol Dial Transplant. 2009, 24: 3360-3366. 10.1093/ndt/gfp271.CrossRefPubMed
25.
go back to reference De Cosmo S, Motterlini N, Prudente S, et al.: BENEDICT Study Group. Impact of the PPAR-gamma2 Pro12Ala polymorphism and ACE inhibitor therapy on new-onset microalbuminuria in type 2 diabetes: evidence from BENEDICT. Diabetes. 2009, 58: 2920-2929. 10.2337/db09-0407.PubMedCentralCrossRefPubMed De Cosmo S, Motterlini N, Prudente S, et al.: BENEDICT Study Group. Impact of the PPAR-gamma2 Pro12Ala polymorphism and ACE inhibitor therapy on new-onset microalbuminuria in type 2 diabetes: evidence from BENEDICT. Diabetes. 2009, 58: 2920-2929. 10.2337/db09-0407.PubMedCentralCrossRefPubMed
26.
go back to reference Liu L, Zheng T, Wang F, et al.: Pro12Ala polymorphism in the PPARG gene contributes to the development of diabetic nephropathy in Chinese type 2 diabetic patients. Diabetes Care. 2010, 33: 144-149. 10.2337/dc09-1258.PubMedCentralCrossRefPubMed Liu L, Zheng T, Wang F, et al.: Pro12Ala polymorphism in the PPARG gene contributes to the development of diabetic nephropathy in Chinese type 2 diabetic patients. Diabetes Care. 2010, 33: 144-149. 10.2337/dc09-1258.PubMedCentralCrossRefPubMed
27.
go back to reference Lapice E, Pinelli M, Riccardi G, Vaccaro O: Pro12Ala polymorphism in the PPARG gene contributes to the development of diabetic nephropathy in Chinese type 2 diabetic patients: comment on the study by Liu et al. Diabetes Care. 2010, 33: e114-10.2337/dc10-0596.CrossRefPubMed Lapice E, Pinelli M, Riccardi G, Vaccaro O: Pro12Ala polymorphism in the PPARG gene contributes to the development of diabetic nephropathy in Chinese type 2 diabetic patients: comment on the study by Liu et al. Diabetes Care. 2010, 33: e114-10.2337/dc10-0596.CrossRefPubMed
28.
go back to reference Zhu W, Ji Y, Bu L, Yang Q: The correlativity study of peroxisome proliferator activated receptor g2 gene polymorphism with susceptibility of diabetic nephropathy in type 2 diabetes mellitus. J Radio-immunology. 2011, 24: 296-298. Zhu W, Ji Y, Bu L, Yang Q: The correlativity study of peroxisome proliferator activated receptor g2 gene polymorphism with susceptibility of diabetic nephropathy in type 2 diabetes mellitus. J Radio-immunology. 2011, 24: 296-298.
29.
go back to reference De Cosmo S, Prudente S, Lamacchia O, et al.: PPAR{gamma}2 P12A polymorphism and albuminuria in patients with type 2 diabetes: a meta-analysis of case–control studies. Nephrol Dial Transplant. 2011, 26: 4011-4016. 10.1093/ndt/gfr187.CrossRefPubMed De Cosmo S, Prudente S, Lamacchia O, et al.: PPAR{gamma}2 P12A polymorphism and albuminuria in patients with type 2 diabetes: a meta-analysis of case–control studies. Nephrol Dial Transplant. 2011, 26: 4011-4016. 10.1093/ndt/gfr187.CrossRefPubMed
30.
go back to reference Zhang H, Zhu S, Chen J, Tang Y, Hu H, Mohan V, Venkatesan R, Wang J, Chen H: Peroxisome Proliferator–Activated Receptor g Polymorphism Pro12Ala Is Associated With Nephropathy in Type 2 Diabetes. Diabetes Care. 2012, 35: 1388-1393. 10.2337/dc11-2142.PubMedCentralCrossRefPubMed Zhang H, Zhu S, Chen J, Tang Y, Hu H, Mohan V, Venkatesan R, Wang J, Chen H: Peroxisome Proliferator–Activated Receptor g Polymorphism Pro12Ala Is Associated With Nephropathy in Type 2 Diabetes. Diabetes Care. 2012, 35: 1388-1393. 10.2337/dc11-2142.PubMedCentralCrossRefPubMed
31.
go back to reference Fujisawa T, Ikegami H, Kawaguchi Y, et al.: Meta-analysis of association of insertion/deletion polymorphism of angiotensin I-con-verting enzyme gene with diabetic nephropathy and retinopathy. Diabetologia. 1998, 41: 47-53. 10.1007/s001250050865.CrossRefPubMed Fujisawa T, Ikegami H, Kawaguchi Y, et al.: Meta-analysis of association of insertion/deletion polymorphism of angiotensin I-con-verting enzyme gene with diabetic nephropathy and retinopathy. Diabetologia. 1998, 41: 47-53. 10.1007/s001250050865.CrossRefPubMed
32.
go back to reference Fei J, Li-Shuai Q, Xi-Zhong S: Association between the methylenetetrahydrofolate reductase C677T polymorphism and hepatocellular carcinoma risk: a meta-analysis. Diagn Pathol. 2009, 4: 39-10.1186/1746-1596-4-39.CrossRef Fei J, Li-Shuai Q, Xi-Zhong S: Association between the methylenetetrahydrofolate reductase C677T polymorphism and hepatocellular carcinoma risk: a meta-analysis. Diagn Pathol. 2009, 4: 39-10.1186/1746-1596-4-39.CrossRef
33.
go back to reference de Matos L, Adriana Del G, Carolina M, de Lima Farah M, Auro Del G, da Silva Pinhal M: Expression of ck-19, galectin-3 and hbme-1 in the differentiation of thyroid lesions: systematic review and diagnostic meta-analysis. Diagn Pathol. 2012, 7: 97-10.1186/1746-1596-7-97.PubMedCentralCrossRefPubMed de Matos L, Adriana Del G, Carolina M, de Lima Farah M, Auro Del G, da Silva Pinhal M: Expression of ck-19, galectin-3 and hbme-1 in the differentiation of thyroid lesions: systematic review and diagnostic meta-analysis. Diagn Pathol. 2012, 7: 97-10.1186/1746-1596-7-97.PubMedCentralCrossRefPubMed
34.
go back to reference Xue Q, Qiliu P, Aiping Q, Zhiping C, Liwen L, Yan D, Li X, Juanjuan X, Haiwei L, Taijie L, Shan L, Jinmin Z: Association of COMT Val158Met polymorphism and breast cancer risk: an updated meta-analysis. Diagn Pathol. 2012, 7: 136-10.1186/1746-1596-7-136.CrossRef Xue Q, Qiliu P, Aiping Q, Zhiping C, Liwen L, Yan D, Li X, Juanjuan X, Haiwei L, Taijie L, Shan L, Jinmin Z: Association of COMT Val158Met polymorphism and breast cancer risk: an updated meta-analysis. Diagn Pathol. 2012, 7: 136-10.1186/1746-1596-7-136.CrossRef
35.
go back to reference Liwa Y, Jianqiu C: Association of MHTFR Ala222Val (rs1801133) polymorphism and breast cancer susceptibility: An update meta-analysis based on 51 research studies. Diagn Pathol. 2012, 7: 171-10.1186/1746-1596-7-171.CrossRef Liwa Y, Jianqiu C: Association of MHTFR Ala222Val (rs1801133) polymorphism and breast cancer susceptibility: An update meta-analysis based on 51 research studies. Diagn Pathol. 2012, 7: 171-10.1186/1746-1596-7-171.CrossRef
Metadata
Title
The association between the PPARγ2 Pro12Ala polymorphism and nephropathy susceptibility in type 2 diabetes: a meta-analysis based on 9,176 subjects
Authors
Lei Wang
Zan Teng
Shuang Cai
Difei Wang
Xin Zhao
Kai Yu
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2013
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/1746-1596-8-118

Other articles of this Issue 1/2013

Diagnostic Pathology 1/2013 Go to the issue