Gene–Gene Interaction between PPARδ and PPARγ Is Associated with Abdominal Obesity in a Chinese Population

a.
Department of Epidemiology, School of Public Health, Soochow University, Suzhou 215123, China
b.
Center for Diseases Control of Jiangsu Province, Nanjing 210009, China
c.
Center for Disease Control of Changzhou, Changzhou 213002, China

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Corresponding author: E-mail address: guozhirong28@163.com (Zhi-Rong Guo)

摘要

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Abstract: The peroxisome proliferator-activated receptors (PPARs) -α, -δ/β and -γ are the ligand-activated transcription factors that function as the master regulators of glucose, fatty acid and lipoprotein metabolism, energy balance, cell proliferation and differentiation, inflammation, and atherosclerosis. The objective of the current study was to examine the main and interactive effect of seven single nucleotide polymorphisms (SNPs) of PPARδ/γ in contribution to abdominal obesity. A total of 820 subjects were randomly selected and no individuals were related. The selected SNPs in PPARδ (rs2016520 and rs9794) and PPARγ (rs10865710, rs1805192, rs709158, rs3856806, and rs4684847) were genotyped. Mean difference and 95% confident interval were calculated. Interactions were explored by the method of generalized multifactor dimensionality reduction. After adjustment for gender, age, and smoking status, it was found that the carriers of the C allele (TC + CC) of rs2016520 were associated with a decreased risk of abdominal obesity compared to the carriers of the TT genotype (mean difference = −2.63, 95% CI = −3.61–−1.64, P < 0.0001). A significant two-locus model (P = 0.0107) involving rs2016520 and rs10865710 and a significant three-locus model (P = 0.0107) involving rs2016520, rs9794, and rs1805192 were observed. Overall, the three-locus model had the highest level of testing accuracy (59.85%) and showed a better cross-validation consistency (9/10) than two-locus model. Therefore, for abdominal obesity defined by waist circumference, we chose the three-locus model as the best interaction model. In conclusion, the C allele in rs2016520 was significantly associated with a lower abdominal obesity. Moreover, an interaction among rs2016520, rs1805192, and rs9794 on incident abdominal obesity could be demonstrated.
- Polymorphism /
- Abdominal obesity /
- Interaction

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参考文献(35)

[1]	Aberle, J., Hopfer, I., Beil, F.U. et al. Association of peroxisome proliferator-activated receptor δ +294T/C with body mass index and interaction with peroxisome proliferator-activated receptor α L162V Int. J. Obes. (Lond.), 30 (2006),pp. 1709-1713
[2]	Altshuler, D., Hirschhorn, J.N., Klannemark, M. et al. Nat. Genet., 26 (2000),pp. 76-80
[3]	Bensinger, S.J., Tontonoz, P. Integration of metabolism and inflammation by lipid-activated nuclear receptors Nature, 454 (2008),pp. 470-477
[4]	Bigaard, J., Tjonneland, A., Thomsen, B.L. et al. Waist circumference, BMI, smoking, and mortality in middle-aged men and women Obes. Res., 11 (2003),pp. 895-903
[5]	Bosse, Y., Despres, J.P., Bouchard, C. et al. The peroxisome proliferator-activated receptor α L162V mutation is associated with reduced adiposity Obes. Res., 11 (2003),pp. 809-816
[6]	Cecil, J.E., Watt, P., Palmer, C.N. et al. Physiol. Behav., 88 (2006),pp. 227-233
[7]	Chen, C.M. Overview of obesity in Mainland China Obes. Rev., 9 (2008),pp. 14-21
[8]	Consilvio, C., Vincent, A.M., Feldman, E.L. Neuroinflammation, COX-2, and ALS – a dual role? Exp. Neurol., 187 (2004),pp. 1-10
[9]	Evans, D., Aberle, J., Wendt, D. et al. J. Mol. Med. (Berl.), 79 (2001),pp. 198-204
[10]	Evans, R.M., Barish, G.D., Wang, Y.X. PPARs and the complex journey to obesity Nat. Med., 10 (2004),pp. 355-361
[11]	Fornage, M., Jacobs, D.R., Steffes, M.W. et al. Metabolism, 54 (2005),pp. 910-917
[12]	Gallicchio, L., Chang, H.H., Christo, D.K. et al. Single nucleotide polymorphisms in obesity-related genes and all-cause and cause-specific mortality: a prospective cohort study BMC Med. Genet., 10 (2009),p. 103
[13]	Hossain, P., Kawar, B., El Nahas, M. Obesity and diabetes in the developing world – a growing challenge N. Engl. J. Med., 356 (2007),pp. 213-215
[14]	Janssen, I., Katzmarzyk, P.T., Ross, R. Waist circumference and not body mass index explains obesity-related health risk Am. J. Clin. Nutr., 79 (2004),pp. 379-384
[15]	Lemay, D.G., Hwang, D.H. Genome-wide identification of peroxisome proliferator response elements using integrated computational genomics J. Lipid. Res., 47 (2006),pp. 1583-1587
[16]
[17]	Lou, X.Y., Chen, G.B., Yan, L. et al. A generalized combinatorial approach for detecting gene-by-gene and gene-by-environment interactions with application to nicotine dependence Am. J. Hum. Genet., 80 (2007),pp. 1125-1137
[18]	Michalik, L., Auwerx, J., Berger, J.P. et al. International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors Pharmacol. Rev., 58 (2006),pp. 726-741
[19]	Michalik, L., Wahli, W. PPARs mediate lipid signaling in inflammation and cancer PPAR Res., 2008 (2008),p. 134059
[20]	, Shenk, J.L., Snaith, M.R., Russell, C.S. et al. A selective peroxisome proliferator-activated receptor δ agonist promotes reverse cholesterol transport Proc. Natl. Acad. Sci. USA, 98 (2001),pp. 5306-5311
[21]	Qi, L., Cho, Y.A. Gene–environment interaction and obesity Nutr. Rev., 66 (2008),pp. 684-694
[22]	Rhee, E.J., Oh, K.W., Lee, W.Y. et al. Effects of two common polymorphisms of peroxisome proliferator-activated receptor-γ gene on metabolic syndrome Arch. Med. Res., 37 (2006),pp. 86-94
[23]	Ricote, M., Glass, C.K. PPARs and molecular mechanisms of transrepression Biochim. Biophys. Acta., 1771 (2007),pp. 926-935
[24]	Ritchie, M.D., Hahn, L.W., Roodi, N. et al. Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer Am. J. Hum. Genet., 69 (2001),pp. 138-147
[25]	Robitaille, J., Gaudet, D., Perusse, L. et al. Features of the metabolic syndrome are modulated by an interaction between the peroxisome proliferator-activated receptor-δ-87T>C polymorphism and dietary fat in French-Canadians Int. J. Obes. (Lond.), 31 (2007),pp. 411-417
[26]	Saez, M.E., Grilo, A., Moron, F.J. et al. Interaction between calpain 5, peroxisome proliferator-activated receptor-γ and peroxisome proliferator-activated receptor-δ genes: a polygenic approach to obesity Cardiovasc. Diabetol., 7 (2008),p. 23
[27]	Shi, Y., Hon, M., Evans, R.M. The peroxisome proliferator-activated receptor δ, an integrator of transcriptional repression and nuclear receptor signaling Proc. Natl. Acad. Sci. USA, 99 (2002),pp. 2613-2618
[28]	Shin, H.D., Park, B.L., Kim, L.H. et al. Genetic polymorphisms in peroxisome proliferator-activated receptor δ associated with obesity Diabetes, 53 (2004),pp. 847-851
[29]	Skogsberg, J., Kannisto, K., Cassel, T.N. et al. Evidence that peroxisome proliferator-activated receptor δ influences cholesterol metabolism in men Arterioscler. Thromb. Vasc. Biol., 23 (2003),pp. 637-643
[30]	Stumvoll, M., Haring, H. The peroxisome proliferator-activated receptor-γ2 Pro12Ala polymorphism Diabetes, 51 (2002),pp. 2341-2347
[31]	Wang, Y.X., Lee, C.H., Tiep, S. et al. Peroxisome-proliferator-activated receptor δ activates fat metabolism to prevent obesity Cell, 113 (2003),pp. 159-170
[32]	Yki-Jarvinen, H. Thiazolidinediones N. Engl. J. Med., 351 (2004),pp. 1106-1118
[33]	Yu, Y.G., Zhu, H.T., Miller, D.T. et al. Age- and gender-dependent obesity in individuals with 16p11.2 deletion J. Genet. Genomics, 38 (2011),pp. 403-409
[34]	Zhou, H., Guo, Z.R., Yu, L.G. et al. Evidence on the applicability of the ATPIII, IDF and CDS metabolic syndrome diagnostic criteria to identify CVD and T2DM in the Chinese population from a 6.3-year cohort study in mid-eastern China Diabetes Res. Clin. Pract., 90 (2010),pp. 319-325
[35]	Zhu, S., Wang, Z., Heshka, S. et al. Waist circumference and obesity-associated risk factors among whites in the third National Health and Nutrition Examination Survey: clinical action thresholds Am. J. Clin. Nutr., 76 (2002),pp. 743-749