A functional GNAQ promoter haplotype is associated with altered Gq expression and with insulin resistance and obesity in women with polycystic ovary syndrome

Pharmacogenetics and Genomics

Volumn 20, Issue 8, 2010, Pages 476-484

  Klenke, Stefanie ^a   Tan, Susanne ^b   Hahn, Susanne ^d   Mann, Klaus ^b   Hauner, Hans ^e   Manthey, Iris ^a   Peters, Jürgen ^c   Siffert, Winfried ^a   Frey, Ulrich H ^a,c  

^a Institut für Pharmakogenetik   (Germany)

^b Bereich Forschung   (Germany)

^c UNIVERSITY HOSPITAL ESSEN   (Germany)

^d Praxis fur Endokrinologie   (Germany)

^e TECHNICAL UNIVERSITY OF MUNICH   (Germany)

Author keywords

allele; body mass index; diplotype; Gq; human; insulin resistance; lipolysis; obesity; polycystic ovary syndrome; polymorphism

Indexed keywords

GUANINE NUCLEOTIDE BINDING PROTEIN; PROTEIN GQ; UNCLASSIFIED DRUG;

ADIPOCYTE; ARTICLE; BODY MASS; GEL MOBILITY SHIFT ASSAY; GENE EXPRESSION; GENETIC LINKAGE; GENETIC POLYMORPHISM; GENOTYPE; HAPLOTYPE; HOMOZYGOSITY; INSULIN RESISTANCE; LIPOLYSIS; OBESITY; OVARY POLYCYSTIC DISEASE; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION;

EID: 77954951848     PISSN: 17446872     EISSN: 17446880     Source Type: Journal    
DOI: 10.1097/FPC.0b013e32833b7497     Document Type: Article

References (34)

1. Wettschureck N, Moers A, Offermanns S. Mouse models to study G-protein-mediated signaling. Pharmacol Ther 2004; 101:75-89.
2. Offermanns S. In vivo functions of heterotrimeric G-proteins: studies in Galpha-deficient mice. Oncogene 2001; 20:1635-1642.
3. Wettschureck N, Rutten H, Zywietz A, Gehring D, Wilkie TM, Chen J, et al. Absence of pressure overload induced myocardial hypertrophy after conditional inactivation of Galphaq/Galpha11 in cardiomyocytes. Nat Med 2001; 7:1236-1240.
4. Offermanns S, Zhao LP, Gohla A, Sarosi I, Simon MI, Wilkie TM. Embryonic cardiomyocyte hypoplasia and craniofacial defects in G alpha q/G alpha 11-mutant mice. EMBO J 1998; 17:4304-4312.
5. Galvin-Parton PA, Chen X, Moxham CM, Malbon CC. Induction of Galphaq-specific antisense RNA in vivo causes increased body mass and hyperadiposity. J Biol Chem 1997; 272:4335-4341.
6. Boschero AC, Szpak-Glasman M, Carneiro EM, Bordin S, Paul I, Rojas E, Atwater I. Oxotremorine-m potentiation of glucose-induced insulin release from rat islets involves M3 muscarinic receptors. Am J Physiol 1995; 268:E336-E342.
7. Duttaroy A, Zimliki CL, Gautam D, Cui Y, Mears D, Wess J. Muscarinic stimulation of pancreatic insulin and glucagon release is abolished in m3 muscarinic acetylcholine receptor-deficient mice. Diabetes 2004; 53:1714-1720.
8. Gregersen S, Thomsen JL, Hermansen K. Endothelin-1 (ET-1)-potentiated insulin secretion: involvement of protein kinase C and the ET(A) receptor subtype. Metabolism 2000; 49:264-269.
9. Imamura T, Vollenweider P, Egawa K, Clodi M, Ishibashi K, Nakashima N, et al. G alpha-q/11 protein plays a key role in insulin-induced glucose transport in 3T3-L1 adipocytes. Mol Cell Biol 1999; 19:6765-6774.
10. Kanzaki M, Watson RT, Artemyev NO, Pessin JE. The trimeric GTP-binding protein (G(q)/G(11)) alpha subunit is required for insulin-stimulated GLUT4 translocation in 3T3L1 adipocytes. J Biol Chem 2000; 275:7167-7175.
11. Frey UH, Lieb W, Erdmann J, Savidou D, Heusch G, Leineweber K, et al. Characterization of the GNAQ promoter and association of increased Gq expression with cardiac hypertrophy in humans. Eur Heart J 2008; 29:888-897.
12. Goodarzi MO, Erickson S, Port SC, Jennrich RI, Korenman SG. Relative impact of insulin resistance and obesity on cardiovascular risk factors in polycystic ovary syndrome. Metabolism 2003; 52:713-719.
13. Hahn S, Tan S, Elsenbruch S, Quadbeck B, Herrmann BL, Mann K, Janssen OE. Clinical and biochemical characterization of women with polycystic ovary syndrome in North Rhine-Westphalia. Horm Metab Res 2005; 37:438-444.
14. Hahn S, Quadbeck B, Elsenbruch S, Gartner R, Finke R, Mann K, Janssen OE. Metformin, an efficacious drug in the treatment of polycystic ovary syndrome. Dtsch Med Wochenschr 2004; 129:1059-1064.
15. Holte J. Disturbances in insulin secretion and sensitivity in women with the polycystic ovary syndrome. Baillieres Clin Endocrinol Metab 1996; 10:221-247.
16. Carmina E. Genetic and environmental aspect of polycystic ovary syndrome. J Endocrinol Invest 2003; 26:1151-1159.
17. Urbanek M, Legro RS, Driscoll DA, Azziz R, Ehrmann DA, Norman RJ, et al. Thirty-seven candidate genes for polycystic ovary syndrome: strongest evidence for linkage is with follistatin. Proc Natl Acad Sci USA 1999; 96:8573-8578.
18. Xita N, Georgiou I, Tsatsoulis A. The genetic basis of polycystic ovary syndrome. Eur J Endocrinol 2002; 147:717-725.
19. Ehrmann DA, Tang X, Yoshiuchi I, Cox NJ, Bell GI. Relationship of insulin receptor substrate-1 and-2 genotypes to phenotypic features of polycystic ovary syndrome. J Clin Endocrinol Metab 2002; 87:4297-4300.
20. Ehrmann DA, Schwarz PE, Hara M, Tang X, Horikawa Y, Imperial J, et al. Relationship of calpain-10 genotype to phenotypic features of polycystic ovary syndrome. J Clin Endocrinol Metab 2002; 87: 1669-1673.
21. Hahn S, Fingerhut A, Khomtsiv U, Khomtsiv L, Tan S, Quadbeck B, et al. The peroxisome proliferator activated receptor gamma Pro12Ala polymorphism is associated with a lower hirsutism score and increased insulin sensitivity in women with polycystic ovary syndrome. Clin Endocrinol (Oxf) 2005; 62:573-579.
22. Hahn S, Frey UH, Siffert W, Tan S, Mann K, Janssen OE. The CC genotype of the GNAS T393C polymorphism is associated with obesity and insulin resistance in women with polycystic ovary syndrome. Eur J Endocrinol 2006; 155:763-770.
23. Siffert W, Forster P, Jockel KH, Mvere DA, Brinkmann B, Naber C, et al. Worldwide ethnic distribution of the G protein beta3 subunit 825T allele and its association with obesity in Caucasian, Chinese, and Black African individuals. J Am Soc Nephrol 1999; 10:1921-1930.
24. Tan S, Hahn S, Benson S, Dietz T, Lahner H, Moeller LC, et al. Metformin improves polycystic ovary syndrome symptoms irrespective of pre-treatment insulin resistance. Eur J Endocrinol 2007; 157:669-676.
25. Frey UH, Bachmann HS, Peters J, Siffert W. PCR-amplification of GC-rich regions: slowdown PCR. Nat Protoc 2008; 3:1312-1317.
26. Hauner H, Rohrig K, Siffert W. Effects of the G-protein beta3 subunit 825T allele on adipogenesis and lipolysis in cultured human preadipocytes and adipocytes. Horm Metab Res 2002; 34:475-480.
27. Gottschling-Zeller H, Birgel M, Scriba D, Blum WF, Hauner H. Depot-specific release of leptin from subcutaneous and omental adipocytes in suspension culture: effect of tumor necrosis factor-alpha and transforming growth factor-beta1. Eur J Endocrinol 1999; 141:436-442.
28. Hellmer J, Arner P, Lundin A. Automatic luminometric kinetic assay of glycerol for lipolysis studies. Anal Biochem 1989; 177:132-137.
29. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005; 21:263-265.
30. Usui I, Imamura T, Huang J, Satoh H, Olefsky JM. Cdc42 is a Rho GTPase family member that can mediate insulin signaling to glucose transport in 3T3-L1 adipocytes. J Biol Chem 2003; 278:13765-13774.
31. Hoffman RP. Indices of insulin action calculated from fasting glucose and insulin reflect hepatic, not peripheral, insulin sensitivity in African-American and Caucasian adolescents. Pediatr Diabetes 2008; 9:57-61.
32. Abdul-Ghani MA, Matsuda M, Balas B, DeFronzo RA. Muscle and liver insulin resistance indexes derived from the oral glucose tolerance test. Diabetes Care 2007; 30:89-94.
33. Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab 2008; 294:E15-E26.
34. Richelsen B, Pedersen SB, Moller-Pedersen T, Bak JF. Regional differences in triglyceride breakdown in human adipose tissue: effects of catecholamines, insulin, and prostaglandin E2. Metabolism 1991; 40:990-996.