Skip to main content
Erschienen in: Endocrine 3/2015

01.04.2015 | Endocrine Genetics/Epigenetics

The Pro12Ala polymorphism in the peroxisome proliferator-activated receptor gamma (PPARG) gene in relation to obesity and metabolic phenotypes in a Taiwanese population

verfasst von: Tun-Jen Hsiao, Eugene Lin

Erschienen in: Endocrine | Ausgabe 3/2015

Einloggen, um Zugang zu erhalten

Abstract

Obesity is considered as an important public health problem in the world. Although the association of a common single nucleotide polymorphism (SNP), rs1801282 (Pro12Ala), in the peroxisome proliferator-activated receptor gamma (PPARG) gene with obesity has been reported in various populations, these data are not conclusive. This study aimed to reassess whether the PPARG rs1801282 SNP is linked with obesity and obesity-related metabolic traits in a Taiwanese population. A total of 674 Taiwanese subjects with general health examinations were genotyped. The rs1801282 genotype was determined by the Taqman SNP genotyping assay. Obesity-related metabolic traits such as triglyceride, waist circumference, systolic and diastolic blood pressure, total cholesterol, and fasting glucose were measured. The PPARG rs1801282 SNP did not exhibit any significant association with obesity among the complete sample population. However, sex-stratified analyses revealed an effect on overweight in female participants where the carriers of the combined CG and GG genotypes had a higher risk to overweight than those with the CC homozygotes (OR = 4.05; 95 % CI = 1.28–12.83; P = 0.017). Compared to the carriers of CC homozygotes, BMI was significantly higher for the carriers of the combined CG and GG genotypes in the female subjects (24.4 ± 3.7 vs. 23.5 ± 3.8 kg/m2; P = 0.033). In addition, the carriers of the CC homozygotes had a higher total cholesterol level than those with the combined CG and GG genotypes in the female subjects (197.0 ± 37.3 vs. 180.7 ± 33.7 mg/dl; P = 0.026). Our study indicates that PPARG rs1801282 may significantly predict overweight, BMI, and total cholesterol in female but not male Taiwanese subjects.
Literatur
1.
Zurück zum Zitat X. Formiguera, A. Cantón, Obesity: epidemiology and clinical aspects. Best Pract. Res. Clin. Gastroenterol. 18(6), 1125–1146 (2004)CrossRefPubMed X. Formiguera, A. Cantón, Obesity: epidemiology and clinical aspects. Best Pract. Res. Clin. Gastroenterol. 18(6), 1125–1146 (2004)CrossRefPubMed
3.
Zurück zum Zitat P. Hossain, Obesity and diabetes in the developing world—a growing challenge. N. Engl. J. Med. 356(3), 973–974 (2007)CrossRef P. Hossain, Obesity and diabetes in the developing world—a growing challenge. N. Engl. J. Med. 356(3), 973–974 (2007)CrossRef
4.
Zurück zum Zitat A.J. Vidal-Puig, R.V. Considine, M. Jimenez-Liñan, A. Werman, W.J. Pories, J.F. Caro, J.S. Flier, Peroxisome proliferator-activated receptor gene expression in human tissues. Effects of obesity, weight loss, and regulation by insulin and glucocorticoids. J. Clin. Invest. 99(10), 2416–2422 (1997)CrossRefPubMedCentralPubMed A.J. Vidal-Puig, R.V. Considine, M. Jimenez-Liñan, A. Werman, W.J. Pories, J.F. Caro, J.S. Flier, Peroxisome proliferator-activated receptor gene expression in human tissues. Effects of obesity, weight loss, and regulation by insulin and glucocorticoids. J. Clin. Invest. 99(10), 2416–2422 (1997)CrossRefPubMedCentralPubMed
5.
Zurück zum Zitat N. Latruffe, J. Vamecq, Peroxisome proliferators and peroxisome proliferator activated receptors (PPARs) as regulators of lipid metabolism. Biochimie 79(2–3), 81–94 (1997)CrossRefPubMed N. Latruffe, J. Vamecq, Peroxisome proliferators and peroxisome proliferator activated receptors (PPARs) as regulators of lipid metabolism. Biochimie 79(2–3), 81–94 (1997)CrossRefPubMed
6.
Zurück zum Zitat S.S. Deeb, L. Fajas, M. Nemoto, J. Pihlajamaki, L. Mykkanen, J. Kuusisto, M. Laakso, W. Fujimoto, J. Auwerx, A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat. Genet. 20(3), 284–287 (1998)CrossRefPubMed S.S. Deeb, L. Fajas, M. Nemoto, J. Pihlajamaki, L. Mykkanen, J. Kuusisto, M. Laakso, W. Fujimoto, J. Auwerx, A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat. Genet. 20(3), 284–287 (1998)CrossRefPubMed
7.
Zurück zum Zitat J. Masugi, Y. Tamori, H. Mori, T. Koike, M. Kasuga, 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. 268(1), 178–182 (2000)CrossRefPubMed J. Masugi, Y. Tamori, H. Mori, T. Koike, M. Kasuga, 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. 268(1), 178–182 (2000)CrossRefPubMed
8.
Zurück zum Zitat M. Stumvoll, H. Häring, The peroxisome proliferator-activated receptor-gamma2 Pro12Ala polymorphism. Diabetes 51(8), 2341–2347 (2002)CrossRefPubMed M. Stumvoll, H. Häring, The peroxisome proliferator-activated receptor-gamma2 Pro12Ala polymorphism. Diabetes 51(8), 2341–2347 (2002)CrossRefPubMed
9.
Zurück zum Zitat A.C. Pereira, R. Oliveira, A.C. Castro, R. Fernandes, Does Pro(12)Ala Polymorphism Enhance the Physiological Role of PPARγ2? PPAR Res. 2013, 401274 (2013)CrossRefPubMedCentralPubMed A.C. Pereira, R. Oliveira, A.C. Castro, R. Fernandes, Does Pro(12)Ala Polymorphism Enhance the Physiological Role of PPARγ2? PPAR Res. 2013, 401274 (2013)CrossRefPubMedCentralPubMed
10.
Zurück zum Zitat B.A. Beamer, C.J. Yen, R.E. Andersen, D. Muller, D. Elahi, L.J. Cheskin, R. Andres, J. Roth, A.R. Shuldiner, Association of the Pro12Ala variant in the peroxisome proliferator-activated receptor-gamma2 gene with obesity in two Caucasian populations. Diabetes 47(11), 1806–1808 (1998)CrossRefPubMed B.A. Beamer, C.J. Yen, R.E. Andersen, D. Muller, D. Elahi, L.J. Cheskin, R. Andres, J. Roth, A.R. Shuldiner, Association of the Pro12Ala variant in the peroxisome proliferator-activated receptor-gamma2 gene with obesity in two Caucasian populations. Diabetes 47(11), 1806–1808 (1998)CrossRefPubMed
11.
Zurück zum Zitat J.L.G. Sánchez, M.S. Ríos, C.F. Perez, M. Laakso, M.T.M. Larrad, Effect of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma-2 gene on adiposity, insulin sensitivity and lipid profile in the Spanish population. Eur. J. Endocrinol. 147(4), 495–501 (2002)CrossRef J.L.G. Sánchez, M.S. Ríos, C.F. Perez, M. Laakso, M.T.M. Larrad, Effect of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma-2 gene on adiposity, insulin sensitivity and lipid profile in the Spanish population. Eur. J. Endocrinol. 147(4), 495–501 (2002)CrossRef
12.
Zurück zum Zitat S. Ben Ali, F. Ben Yahia, Y. Sediri, A. Kallel, B. Ftouhi, M. Feki, M. Elasmi, S. Haj-Taieb, O. Souheil, H. Sanhagi, H. Slimane, R. Jemaa, N. Kaabachi, Gender-specific effect of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma-2 gene on obesity risk and leptin levels in a Tunisian population. Clin. Biochem. 42(16–17), 1642–1647 (2009)CrossRefPubMed S. Ben Ali, F. Ben Yahia, Y. Sediri, A. Kallel, B. Ftouhi, M. Feki, M. Elasmi, S. Haj-Taieb, O. Souheil, H. Sanhagi, H. Slimane, R. Jemaa, N. Kaabachi, Gender-specific effect of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma-2 gene on obesity risk and leptin levels in a Tunisian population. Clin. Biochem. 42(16–17), 1642–1647 (2009)CrossRefPubMed
13.
Zurück zum Zitat H. Mirzaei, S.M. Akrami, T. Golmohammadi, M. Doosti, R. Heshmat, M. Nakhjavani, P. Amiri, Polymorphism of Pro12Ala in the peroxisome proliferator-activated receptor gamma2 gene in Iranian diabetic and obese subjects. Metab. Syndr. Relat. Disord. 7(5), 453–458 (2009)CrossRefPubMed H. Mirzaei, S.M. Akrami, T. Golmohammadi, M. Doosti, R. Heshmat, M. Nakhjavani, P. Amiri, Polymorphism of Pro12Ala in the peroxisome proliferator-activated receptor gamma2 gene in Iranian diabetic and obese subjects. Metab. Syndr. Relat. Disord. 7(5), 453–458 (2009)CrossRefPubMed
14.
Zurück zum Zitat J. Prakash, N. Srivastava, S. Awasthi, C. Agarwal, S. Natu, N. Rajpal, B. Mittal, Association of PPAR-γ gene polymorphisms with obesity and obesity-associated phenotypes in North Indian population. Am. J. Hum. Biol. 24(4), 454–459 (2012)CrossRefPubMed J. Prakash, N. Srivastava, S. Awasthi, C. Agarwal, S. Natu, N. Rajpal, B. Mittal, Association of PPAR-γ gene polymorphisms with obesity and obesity-associated phenotypes in North Indian population. Am. J. Hum. Biol. 24(4), 454–459 (2012)CrossRefPubMed
15.
Zurück zum Zitat S.P. Bhatt, A. Misra, M. Sharma, K. Luthra, R. Guleria, R.M. Pandey, N.K. Vikram, Ala/Ala genotype of Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-γ2 gene is associated with obesity and insulin resistance in Asian Indians. Diabetes Technol. Ther. 14(9), 828–834 (2012)CrossRefPubMedCentralPubMed S.P. Bhatt, A. Misra, M. Sharma, K. Luthra, R. Guleria, R.M. Pandey, N.K. Vikram, Ala/Ala genotype of Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-γ2 gene is associated with obesity and insulin resistance in Asian Indians. Diabetes Technol. Ther. 14(9), 828–834 (2012)CrossRefPubMedCentralPubMed
16.
Zurück zum Zitat O. Vaccaro, F.P. Mancini, G. Ruffa, L. Sabatino, V. Colantuoni, G. Riccardi, Pro12Ala mutation in the peroxisome proliferator-activated receptor gamma2 (PPARgamma2) and severe obesity: a case-control study. Int. J. Obes. Relat. Metab. Disord. 24(9), 1195–1199 (2000)CrossRefPubMed O. Vaccaro, F.P. Mancini, G. Ruffa, L. Sabatino, V. Colantuoni, G. Riccardi, Pro12Ala mutation in the peroxisome proliferator-activated receptor gamma2 (PPARgamma2) and severe obesity: a case-control study. Int. J. Obes. Relat. Metab. Disord. 24(9), 1195–1199 (2000)CrossRefPubMed
17.
Zurück zum Zitat E.Y. Oh, K.M. Min, J.H. Chung, Y.K. Min, M.S. Lee, K.W. Kim, M.K. Lee, Significance of Pro12Ala mutation in peroxisome proliferator-activated receptor-gamma2 in Korean diabetic and obese subjects. J. Clin. Endocrinol. Metab. 85(5), 1801–1804 (2000)PubMed E.Y. Oh, K.M. Min, J.H. Chung, Y.K. Min, M.S. Lee, K.W. Kim, M.K. Lee, Significance of Pro12Ala mutation in peroxisome proliferator-activated receptor-gamma2 in Korean diabetic and obese subjects. J. Clin. Endocrinol. Metab. 85(5), 1801–1804 (2000)PubMed
18.
Zurück zum Zitat K. Clement, S. Hercberg, B. Passinge, P. Galan, M. Varroud-Vial, A.R. Shuldiner, B.A. Beamer, G. Charpentier, B. Guy-Grand, P. Froguel, C. Vaisse, The Pro115Gln and Pro12Ala PPAR gamma gene mutations in obesity and type 2 diabetes. Int. J. Obes. Relat. Metab. Disord. 24(3), 391–393 (2000)CrossRefPubMed K. Clement, S. Hercberg, B. Passinge, P. Galan, M. Varroud-Vial, A.R. Shuldiner, B.A. Beamer, G. Charpentier, B. Guy-Grand, P. Froguel, C. Vaisse, The Pro115Gln and Pro12Ala PPAR gamma gene mutations in obesity and type 2 diabetes. Int. J. Obes. Relat. Metab. Disord. 24(3), 391–393 (2000)CrossRefPubMed
19.
Zurück zum Zitat M. Ghoussaini, D. Meyre, S. Lobbens, G. Charpentier, K. Clément, M.A. Charles, M. Tauber, J. Weill, P. Froguel, Implication of the Pro12Ala polymorphism of the PPAR-gamma 2 gene in type 2 diabetes and obesity in the French population. BMC Med. Genet. 6, 11 (2005)CrossRefPubMedCentralPubMed M. Ghoussaini, D. Meyre, S. Lobbens, G. Charpentier, K. Clément, M.A. Charles, M. Tauber, J. Weill, P. Froguel, Implication of the Pro12Ala polymorphism of the PPAR-gamma 2 gene in type 2 diabetes and obesity in the French population. BMC Med. Genet. 6, 11 (2005)CrossRefPubMedCentralPubMed
20.
Zurück zum Zitat M.M. Swarbrick, C.M. Chapman, B.M. McQuillan, J. Hung, P.L. Thompson, J.P. Beilby, A Pro12Ala polymorphism in the human peroxisome proliferator-activated receptor-gamma 2 is associated with combined hyperlipidaemia in obesity. Eur. J. Endocrinol. 144(3), 277–282 (2001)CrossRefPubMed M.M. Swarbrick, C.M. Chapman, B.M. McQuillan, J. Hung, P.L. Thompson, J.P. Beilby, A Pro12Ala polymorphism in the human peroxisome proliferator-activated receptor-gamma 2 is associated with combined hyperlipidaemia in obesity. Eur. J. Endocrinol. 144(3), 277–282 (2001)CrossRefPubMed
21.
Zurück zum Zitat F.F. Carlos, J. Silva-Nunes, O. Flores, M. Brito, G. Doria, L. Veiga, P.V. Baptista, Association of FTO and PPARG polymorphisms with obesity in Portuguese women. Diabetes Metab. Syndr. Obes. 6, 241–245 (2013)PubMedCentralPubMed F.F. Carlos, J. Silva-Nunes, O. Flores, M. Brito, G. Doria, L. Veiga, P.V. Baptista, Association of FTO and PPARG polymorphisms with obesity in Portuguese women. Diabetes Metab. Syndr. Obes. 6, 241–245 (2013)PubMedCentralPubMed
22.
Zurück zum Zitat T.J. Hsiao, Y. Hwang, C.H. Liu, H.M. Chang, E. Lin, Association of the C825T polymorphism in the GNB3 gene with obesity and metabolic phenotypes in a Taiwanese population. Genes Nutr. 8(1), 137–144 (2013)CrossRefPubMedCentralPubMed T.J. Hsiao, Y. Hwang, C.H. Liu, H.M. Chang, E. Lin, Association of the C825T polymorphism in the GNB3 gene with obesity and metabolic phenotypes in a Taiwanese population. Genes Nutr. 8(1), 137–144 (2013)CrossRefPubMedCentralPubMed
24.
Zurück zum Zitat L.S. Wu, C.H. Hsieh, D. Pei, Y.J. Hung, S.W. Kuo, E. Lin, Association and interaction analyses of genetic variants in ADIPOQ, ENPP1, GHSR, PPAR{gamma} and TCF7L2 genes for diabetic nephropathy in a Taiwanese population with type 2 diabetes. Nephrol. Dial. Transplant. 24(11), 3360–3366 (2009)CrossRefPubMed L.S. Wu, C.H. Hsieh, D. Pei, Y.J. Hung, S.W. Kuo, E. Lin, Association and interaction analyses of genetic variants in ADIPOQ, ENPP1, GHSR, PPAR{gamma} and TCF7L2 genes for diabetic nephropathy in a Taiwanese population with type 2 diabetes. Nephrol. Dial. Transplant. 24(11), 3360–3366 (2009)CrossRefPubMed
25.
Zurück zum Zitat D.J. Hsiao, L.S. Wu, S.Y. Huang, E. Lin, Weight loss and body fat reduction under sibutramine therapy in obesity with the C825T polymorphism in the GNB3 gene. Pharmacogenet. Genomics 19(9), 730–733 (2009)CrossRefPubMed D.J. Hsiao, L.S. Wu, S.Y. Huang, E. Lin, Weight loss and body fat reduction under sibutramine therapy in obesity with the C825T polymorphism in the GNB3 gene. Pharmacogenet. Genomics 19(9), 730–733 (2009)CrossRefPubMed
26.
Zurück zum Zitat R. Valve, K. Sivenius, R. Miettinen, J. Pihlajamäki, A. Rissanen, S.S. Deeb, J. Auwerx, M. Uusitupa, M. Laakso, Two polymorphisms in the peroxisome proliferator-activated receptor-gamma gene are associated with severe overweight among obese women. J. Clin. Endocrinol. Metab. 84(10), 3708–3712 (1999)PubMed R. Valve, K. Sivenius, R. Miettinen, J. Pihlajamäki, A. Rissanen, S.S. Deeb, J. Auwerx, M. Uusitupa, M. Laakso, Two polymorphisms in the peroxisome proliferator-activated receptor-gamma gene are associated with severe overweight among obese women. J. Clin. Endocrinol. Metab. 84(10), 3708–3712 (1999)PubMed
27.
Zurück zum Zitat T.J. Hsiao, E. Lin, Evaluation of the glutamine 27 glutamic acid polymorphism in the adrenoceptor beta 2 surface gene on obesity and metabolic phenotypes in Taiwan. J. Investig. Med. 62(2), 310–315 (2014)PubMed T.J. Hsiao, E. Lin, Evaluation of the glutamine 27 glutamic acid polymorphism in the adrenoceptor beta 2 surface gene on obesity and metabolic phenotypes in Taiwan. J. Investig. Med. 62(2), 310–315 (2014)PubMed
28.
Zurück zum Zitat T.J. Hsiao, Y. Hwang, H.M. Chang, E. Lin, Association of the rs6235 variant in the proprotein convertase subtilisin/kexin type 1 (PCSK1) gene with obesity and related traits in a Taiwanese population. Gene 533(1), 32–37 (2014)CrossRefPubMed T.J. Hsiao, Y. Hwang, H.M. Chang, E. Lin, Association of the rs6235 variant in the proprotein convertase subtilisin/kexin type 1 (PCSK1) gene with obesity and related traits in a Taiwanese population. Gene 533(1), 32–37 (2014)CrossRefPubMed
29.
Zurück zum Zitat H.Y. Lane, G.E. Tsai, E. Lin, Assessing gene–gene interactions in pharmacogenomics. Mol. Diagn. Ther. 16(1), 15–27 (2012)CrossRefPubMed H.Y. Lane, G.E. Tsai, E. Lin, Assessing gene–gene interactions in pharmacogenomics. Mol. Diagn. Ther. 16(1), 15–27 (2012)CrossRefPubMed
30.
Zurück zum Zitat E. Lin, D. Pei, Y.J. Huang, C.H. Hsieh, L.S. Wu, Gene-gene interactions among genetic variants from obesity candidate genes for nonobese and obese populations in type 2 diabetes. Genet. Test Mol. Biomark. 13(4), 485–493 (2009)CrossRef E. Lin, D. Pei, Y.J. Huang, C.H. Hsieh, L.S. Wu, Gene-gene interactions among genetic variants from obesity candidate genes for nonobese and obese populations in type 2 diabetes. Genet. Test Mol. Biomark. 13(4), 485–493 (2009)CrossRef
31.
Zurück zum Zitat Y.J. Liou, Y.M. Bai, E. Lin, J.Y. Chen, T.T. Chen, C.J. Hong, S.J. Tsai, Gene-gene interactions of the INSIG1 and INSIG2 in metabolic syndrome in schizophrenic patients treated with atypical antipsychotics. Pharmacogenomics J. 12(1), 54–61 (2012)CrossRefPubMed Y.J. Liou, Y.M. Bai, E. Lin, J.Y. Chen, T.T. Chen, C.J. Hong, S.J. Tsai, Gene-gene interactions of the INSIG1 and INSIG2 in metabolic syndrome in schizophrenic patients treated with atypical antipsychotics. Pharmacogenomics J. 12(1), 54–61 (2012)CrossRefPubMed
Metadaten
Titel
The Pro12Ala polymorphism in the peroxisome proliferator-activated receptor gamma (PPARG) gene in relation to obesity and metabolic phenotypes in a Taiwanese population
verfasst von
Tun-Jen Hsiao
Eugene Lin
Publikationsdatum
01.04.2015
Verlag
Springer US
Erschienen in
Endocrine / Ausgabe 3/2015
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-014-0407-7

Weitere Artikel der Ausgabe 3/2015

Endocrine 3/2015 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.