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Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2011

Open Access 01-12-2011 | Research

Association of TRB3 Q84R polymorphism with polycystic ovary syndrome in Chinese women

Authors: Xue Zhang, Li Fu, Qiufang Zhang, Liying Yan, Yanmin Ma, Binbin Tu, Nana Liu, Jie Qiao

Published in: Reproductive Biology and Endocrinology | Issue 1/2011

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Abstract

Background

Tribbles 3 (TRB3) affects insulin signalling by inhibiting insulin-stimulated Akt phosphorylation and subsequent activation. A single nucleotide polymorphism located in the second extron of the human TRB3 gene is thought to be associated with insulin resistance. The latter is a core abnormality in PCOS independent of obesity. The present study was designed to clarify the relationships of TRB3 Q84R polymorphism with PCOS in a Chinese women group.

Methods

A case-control study with two groups: PCOS group (n = 336) and control group of infertility women for tubal and/or male factor (n = 116) was performed. Genotyping of the TRB3 R84 variant was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results

The frequency of genotype QQ in PCOS women was significantly lower, while genotype QR and RR were significantly higher than that in control group (p < 0.05). However, the difference disappeared after adjustment for BMI. At glucose1h, glucose2h and insulin2h point, the difference between QQ individuals and R84 allele carriers in PCOS women reached statistical significance during OGTT (p < 0.05).

Conclusions

TRB3 Q84R polymorphism is associated with obesity and especially glucose metabolism and not associated with polycystic ovary syndrome because of compositional characteristics of phenotype in Chinese PCOS women.
Appendix
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Literature
1.
2.
Diamanti-Kandarakis E, Piperi C: Genetics of polycystic ovary syndrome: searching for the way out of the labyrinth. Hum Reprod Update. 2005, 11: 631-643. 10.1093/humupd/dmi025.CrossRefPubMed
3.
Legro RS, Strauss JF: Molecular progress in infertility: polycystic ovary syndrome. Fertil Steril. 2002, 78: 569-576. 10.1016/S0015-0282(02)03275-2.CrossRefPubMed
4.
Legro RS, Castracane VD, Kauffman RP: Detecting insulin resistance in polycystic ovary syndrome: purposes and pitfalls. Obstet Gynecol Surv. 2004, 59: 141-154. 10.1097/01.OGX.0000109523.25076.E2.CrossRefPubMed
5.
Chang RJ, Nakamura RM, Judd HL, Kaplan SA: Insulin resistance in nonobese patients with polycystic ovarian disease. J Clin Endocrinol Metab. 1983, 57: 356-359. 10.1210/jcem-57-2-356.CrossRefPubMed
6.
Dunaif A: Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev. 1997, 18: 774-800. 10.1210/er.18.6.774.PubMed
7.
Poretsky L, Cataldo N, Rosenwaks Z, Guidice L: The insulin-related ovarian regulatory system in health and disease. Endocr Rev. 1999, 20: 532-582. 10.1210/er.20.4.535.
8.
The Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group: Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004, 19: 41-47. 10.1093/humrep/deh098.CrossRef
9.
Du K, Herzig S, Kulkarni RN, Montminy M: TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver. Science. 2003, 300: 1574-1577. 10.1126/science.1079817.CrossRefPubMed
10.
Yao XH, Grégoire Nyomba BL: Abnormal glucose homeostasis in adult female rat offspring after intrauterine ethanol exposure. Am J Physiol Regul Integr Comp Physiol. 2007, 292: R1926-1933. 10.1152/ajpregu.00822.2006.CrossRefPubMed
11.
Yao XH, Nyomba BL: Hepatic insulin resistance induced by prenatal alcohol exposure is associated with reduced PTEN and TRB3 acetylation in adult rat offspring. Am J Physiol Regul Integr Comp Physiol. 2008, 294: R1797-1806. 10.1152/ajpregu.00804.2007.CrossRefPubMed
12.
Oberkofler H, Pfeifenberger A, Soyal S, Felder T, Hahne P, Miller K, Krempler F, Patsch W: Aberrant hepatic TRIB3 gene expression in insulin-resistant obese humans. Diabetologia. 2010, 53: 1971-1975. 10.1007/s00125-010-1772-2.CrossRefPubMed
13.
Liu J, Wu X, Franklin JL, Messina JL, Hill HS, Moellering DR, Walton RG, Martin M, Garvey WT: Mammalian Tribbles homolog 3 impairs insulin action in skeletal muscle: role in glucose-induced insulin resistance. Am J Physiol Endocrinol Metab. 2010, 298: E565-E576. 10.1152/ajpendo.00467.2009.PubMedCentralCrossRefPubMed
14.
Prudente S, Hribal ML, Flex E, Turchi F, Morini E, De Cosmo S, Bacci S, Tassi V, Cardellini M, Lauro R, Sesti G, Dallapiccola B, Trischitta V: The functional Q84R polymorphism of mammalian Tribbles homolog TRB3 is associated with insulin resistance and related cardiovascular risk in Caucasians from Italy. Diabetes. 2005, 54: 2807-2811. 10.2337/diabetes.54.9.2807.CrossRefPubMed
15.
Andreozzi F, Formoso G, Prudente S, Hribal ML, Pandolfi A, Bellacchio E, Di Silvestre S, Trischitta V, Consoli A, Sesti G: TRIB3 R84 variant is associated with impaired insulin-mediated nitric oxide production in human endothelial cells. Arterioscler Thromb Vasc Biol. 2008, 28: 1355-1360. 10.1161/ATVBAHA.108.162883.CrossRefPubMed
16.
Shi Z, Liu J, Guo Q, Ma X, Shen L, Xu S, Gao H, Yuan X, Zhang J: Association of TRB3 gene Q84R polymorphism with type 2 diabetes mellitus in Chinese population. Endocrine. 2009, 35: 414-419. 10.1007/s12020-009-9162-6.CrossRefPubMed
17.
Prudente S, Scarpelli D, Chandalia M, Zhang YY, Morini E, Del Guerra S, Perticone F, Li R, Powers C, Andreozzi F, Marchetti P, Dallapiccola B, Abate N, Doria A, Sesti G, Trischitta V: The TRIB3 Q84R polymorphism and risk of early-onset type 2 diabetes. J Clin Endocrinol Metab. 2009, 94: 190-196. 10.1210/jc.2008-1365.PubMedCentralCrossRefPubMed
18.
Gong HP, Wang ZH, Jiang H, Fang NN, Li JS, Shang YY, Zhang Y, Zhong M, Zhang W: TRIB3 functional Q84R polymorphism is a risk factor for metabolic syndrome and carotid atherosclerosis. Diabetes Care. 2009, 32: 1311-1313. 10.2337/dc09-0061.PubMedCentralCrossRefPubMed
19.
Liew CW, Bochenski J, Kawamori D, Hu J, Leech CA, Wanic K, Malecki M, Warram JH, Qi L, Krolewski AS, Kulkarni RN: The pseudokinase tribbles homolog 3 interacts with ATF4 to negatively regulate insulin exocytosis in human and mouse beta cells. J Clin Invest. 2010, 120: 2876-2888. 10.1172/JCI36849.PubMedCentralCrossRefPubMed
20.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985, 28: 412-419. 10.1007/BF00280883.CrossRefPubMed
21.
Miller SA, Dykes DD, Polesky H: A salting procedure for extracting DNA from nucleated cells. Nucleic Acid Res. 1998, 16: 1215-10.1093/nar/16.3.1215.CrossRef
22.
Zhao S, Qiao J, Li M, Zhang X, Yu J, Li R: Discovery of distinct protein profiles for polycystic ovary syndrome with and without insulin resistance by surface-enhanced laser adsorption/ionization time of flight mass spectrometry. Fertil Steril. 2007, 88: 145-151. 10.1016/j.fertnstert.2006.11.207.CrossRefPubMed
23.
Dunaif A, Finegood DT: Beta-cell dysfunction independent of obesity and glucose intolerance in the polycystic ovary syndrome. J Clin Endocrinol Metab. 1996, 81: 942-947. 10.1210/jc.81.3.942.PubMed
24.
Goodarzi MO, Erickson S, Port SC, Jennrich RI, Korenman SG: beta-cell function: a key pathological determinant in polycystic ovary syndrome. J Clin Endocrinol Metab. 2005, 90: 310-315. 10.1210/jc.2004-1006.CrossRefPubMed
25.
Waterworth DM, Bennett ST, Gharani N, McCarthy MI, Hague S, Batty S, Conway GS, White D, Todd JA, Franks S, Williamson R: Linkage and association of insulin gene VNTR regulatory polymorphism with polycystic ovary syndrome. Lancet. 1997, 349: 986-990. 10.1016/S0140-6736(96)08368-7.CrossRefPubMed
26.
Urbanek M, Legro RS, Driscoll DA, Azziz R, Ehrmann DA, Norman RJ: Thirty-seven candidate genes for polycystic ovary syndrome: strongest evidence for linkage is with follistatin. Proc Natl Acad Sci USA. 1999, 96: 8573-8578. 10.1073/pnas.96.15.8573.PubMedCentralCrossRefPubMed
27.
Ehrmann DA, Schwarz PE, Hara M, Tang X, Horikawa Y, Imperial J: Relationship of calpain-10 genotype to phenotypic features of polycystic ovary syndrome. J Clin Endocrinol Metab. 2002, 87: 1669-1673. 10.1210/jc.87.4.1669.CrossRefPubMed
28.
Dilek S, Ertunc D, Tok EC, Erdal EM, Aktas A: Association of Gly972Arg variant of insulin receptor substrate-1 with metabolic features in women with polycystic ovary syndrome. Fertil Steril. 2005, 84: 407-412. 10.1016/j.fertnstert.2005.01.133.CrossRefPubMed
29.
Saltiel AR: Putting the brakes on insulin signaling. N Engl J Med. 2003, 349: 2560-2562. 10.1056/NEJMcibr031668.CrossRefPubMed
30.
Permutt MA, Wasson JC, Suarez BK, Lin J, Thomas J, Meyer J, Lewitzky S, Rennich JS, Parker A, DuPrat L, Maruti S, Chayen S, Glaser B: A genome scan for type 2 diabetes susceptibility loci in a genetically isolated population. Diabetes. 2001, 50: 681-685. 10.2337/diabetes.50.3.681.CrossRefPubMed
31.
Waldstreicher J, Santoro NF, Hall JE, Filicori M, Crowley WF: Hyperfunction of the hypothalamic-pituitary axis in women with polycystic ovarian disease: indirect evidence for partial gonadotroph desensitization. J Clin Endocrinol Metab. 1988, 66: 165-172. 10.1210/jcem-66-1-165.CrossRefPubMed
32.
National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002, 106: 3143-3421.
33.
Zawadzki JK, Dunaif A: Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. Polycystic Ovary Syndrome. Edited by: Dunaif A, Givens JR, Haseltine FP, Merriam GR. 1992, Boston: Blackwell Scientific Publications, 377-384.
34.
Dewailly D, Catteau-Jonard S, Reyss AC, Leroy M, Pigny P: Oligoanovulation with polycystic ovaries but not overt hyperandrogenism. J Clin Endocrinol Metab. 2006, 91: 3922-3927. 10.1210/jc.2006-1054.CrossRefPubMed
35.
Zhang HY, Zhu FF, Xiong J, Shi XB, Fu SX: Characteristics of different phenotypes of polycystic ovary syndrome based on the Rotterdam criteria in a large-scale Chinese population. BJOG. 2009, 116: 1633-1639. 10.1111/j.1471-0528.2009.02347.x.CrossRefPubMed
36.
Guastella E, Longo RA, Carmina E: Clinical and endocrine characteristics of the main polycystic ovary syndrome phenotypes. Fertil Steril. 2010, 94: 2197-2201. 10.1016/j.fertnstert.2010.02.014.CrossRefPubMed
Metadata
Title
Association of TRB3 Q84R polymorphism with polycystic ovary syndrome in Chinese women
Authors
Xue Zhang
Li Fu
Qiufang Zhang
Liying Yan
Yanmin Ma
Binbin Tu
Nana Liu
Jie Qiao
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2011
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-9-46

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