Abstract
CREB-regulated transcription coactivator 3 (CRTC3) was a recently identified protein which played an important role in glucose and lipid metabolism. Previous research showed that the polymorphisms of CRTC3 were associated with obesity in Mexican-Americans. Data on that relationship in Chinese was unavailable so far. So we investigated whether the polymorphisms of CRTC3 could confer risks of obesity or other metabolic disorders in Chinese population. 1,550 subjects were recruited from physical examination participants. Two SNPs of CRTC3, rs3862434 and rs11635252, were genotyped with the method of PCR–RFLP. Logistic regression model was applied to calculate the risks of overweight, obesity and dyslipidemias for genotypes. The rs3862434 was significantly associated with the plasma level of total cholesterol (P = 0.026), with the G allele carriers having a lower level compared with the AA genotype (P = 0.018). The rs11635252 was associated with the risks of overweight and hypertriglyceridemia, specifically, T allele had higher risks of overweight and hypertriglyceridemia compared with C allele (OR 1.23, 95 % CI 1.02–1.48, P = 0.024; OR 1.22, 95 % CI 1.00–1.48, P = 0.048, respectively). In conclusion, the CRTC3 polymorphism rs3862434 was associated with the plasma level of total cholesterol, and rs11635252 was associated with the risks of overweight and hypertriglyceridemia in a Chinese Han population, which might strengthen our understanding of the complex heredity of metabolic disorders.
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Abbreviations
- CREB:
-
Cyclic AMP-responsive element-binding proteins
- CRTC3:
-
CREB-regulated transcription coactivator 3
- PCR–RFLP:
-
PCR–restriction fragment length polymorphism
- SNP:
-
Single nucleotide polymorphism
- BMI:
-
Body mass index
References
Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C (2004) Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American heart association conference on scientific issues related to definition. Circulation 109:433–438
James WP (2008) The epidemiology of obesity: the size of the problem. J Intern Med 263:336–352
Iourgenko V, Zhang W, Mickanin C, Daly I, Jiang C, Hexham JM, Orth AP, Miraglia L, Meltzer J, Garza D, Chirn GW, McWhinnie E, Cohen D, Skelton J, Terry R, Yu Y, Bodian D, Buxton FP, Zhu J, Song C, Labow MA (2003) Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells. Proc Natl Acad Sci USA 100:12147–12152
Screaton RA, Conkright MD, Katoh Y, Best JL, Canettieri G, Jeffries S, Guzman E, Niessen S, Yates JR III, Takemori H, Okamoto M, Montminy M (2004) The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector. Cell 119:61–74
Herzig S, Long F, Jhala US, Hedrick S, Quinn R, Bauer A, Rudolph D, Schutz G, Yoon C, Puigserver P, Spiegelman B, Montminy M (2001) CREB regulates hepatic gluconeogenesis through the coactivator PGC-1. Nature 413:179–183
Yoon JC, Puigserver P, Chen G, Donovan J, Wu Z, Rhee J, Adelmant G, Stafford J, Kahn CR, Granner DK, Newgard CB, Spiegelman BM (2001) Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 413:131–138
Song Y, Altarejos J, Goodarzi MO, Inoue H, Guo X, Berdeaux R, Kim JH, Goode J, Igata M, Paz JC, Hogan MF, Singh PK, Goebel N, Vera L, Miller N, Cui J, Jones MR, Chen YD, Taylor KD, Hsueh WA, Rotter JI, Montminy M (2010) CRTC3 links catecholamine signalling to energy balance. Nature 468:933–939
Bachman ES, Dhillon H, Zhang CY, Cinti S, Bianco AC, Kobilka BK, Lowell BB (2002) betaAR signaling required for diet-induced thermogenesis and obesity resistance. Science 297:843–845
Wu Z, Huang X, Feng Y, Handschin C, Gullicksen PS, Bare O, Labow M, Spiegelman B, Stevenson SC (2006) Transducer of regulated CREB-binding proteins (TORCs) induce PGC-1alpha transcription and mitochondrial biogenesis in muscle cells. Proc Natl Acad Sci USA 103:14379–14384
Than TA, Lou H, Ji C, Win S, Kaplowitz N (2011) Role of cAMP-responsive element-binding protein (CREB)-regulated transcription coactivator 3 (CRTC3) in the initiation of mitochondrial biogenesis and stress response in liver cells. J Biol Chem 286:22047–22054
Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa F (2005) Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation 112:2735–2752
Altarejos JY, Montminy M (2011) CREB and the CRTC co-activators: sensors for hormonal and metabolic signals. Nat Rev Mol Cell Biol 12:141–151
Vega RB, Huss JM, Kelly DP (2000) The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Mol Cell Biol 20:1868–1876
Herzig S, Hedrick S, Morantte I, Koo SH, Galimi F, Montminy M (2003) CREB controls hepatic lipid metabolism through nuclear hormone receptor PPAR-gamma. Nature 426:190–193
Nishizuka M, Honda K, Tsuchiya T, Nishihara T, Imagawa M (2001) RGS2 promotes adipocyte differentiation in the presence of ligand for peroxisome proliferator-activated receptor gamma. J Biol Chem 276:29625–29627
Deverey R, O’Donnell L, Tomkin GH (1986) Effect of catecholamines on the hepatic rate-limiting enzymes of cholesterol metabolism in normally fed and cholesterol-fed rabbits. Biochim Biophys Acta 887:173–181
Ernsberger P, Johnson JL, Rosenthal T, Mirelman D, Koletsky RJ (2007) Therapeutic actions of allylmercaptocaptopril and captopril in a rat model of metabolic syndrome. Am J Hypertens 20:866–874
Krone W, Naegele H, Behnke B, Greten H (1988) Opposite effects of insulin and catecholamines on LDL-receptor activity in human mononuclear leukocytes. Diabetes 37:1386–1391
O’Donnell L, Owens D, McGee C, Devery R, Hession P, Collins P, Johnson A, Tomkin G (1988) Effects of catecholamines on serum lipoproteins of normally fed and cholesterol-fed rabbits. Metabolism 37:910–915
Sun T, Gao Y, Tan W, Ma S, Shi Y, Yao J, Guo Y, Yang M, Zhang X, Zhang Q, Zeng C, Lin D (2007) A six-nucleotide insertion-deletion polymorphism in the CASP8 promoter is associated with susceptibility to multiple cancers. Nat Genet 39:605–613
Chiolero A, Faeh D, Paccaud F, Cornuz J (2008) Consequences of smoking for body weight, body fat distribution, and insulin resistance. Am J Clin Nutr 87:801–809
Acknowledgments
This work was supported by National Basic Research Program of China (No. 2012CB518200) and National Natural Science Foundation of China (No. 81272180).
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The authors declare no conflicts of interest.
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Zejin Ou and Guanghai Wang have contributed equally to this study.
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Ou, Z., Wang, G., Li, Q. et al. CRTC3 polymorphisms were associated with the plasma level of total cholesterol and the risks of overweight and hypertriglyceridemia in a Chinese Han population. Mol Biol Rep 41, 125–130 (2014). https://doi.org/10.1007/s11033-013-2844-4
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DOI: https://doi.org/10.1007/s11033-013-2844-4