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Pro12Ala polymorphism in human peroxisome proliferator activated receptor gamma is associated with hyperlipidaemia in obstructive sleep apnoea hypopnoea syndrome

  • J Guan (a1), H Yi (a1), X Wu (a2), K Su (a1), M Tao (a3) and S Yin (a1)...



Peroxisome proliferator activated receptor gamma is a ligand-dependent transcription factor with an important role in insulin resistance and obesity. We investigated the associations between the Pro12Ala polymorphism of this receptor, obstructive sleep apnoea hypopnoea syndrome and hyperlipidaemia risk factors, in a Chinese cohort.

Subjects and methods:

We recruited 420 obstructive sleep apnoea hypopnoea syndrome patients and 190 healthy controls. Genetic analysis was conducted by restriction fragment length polymorphism. The hyperlipidaemia risk in both the study and control groups was analysed.


Comparison of genotype and allele frequencies revealed no significant differences between patients and controls (p > 0.05). In patients, there was no correlation between genotype and clinical parameters (p > 0.05), apart from a significant association between the Ala12 allele and hyperlipidaemia (odds ratio = 2.181; p = 0.017; 95 per cent confidence interval = 1.133–4.198).


In this Chinese cohort, the Pro12Ala polymorphism of peroxisome proliferator activated receptor gamma was not associated with obstructive sleep apnoea hypopnoea syndrome, but was associated with increased hyperlipidaemia risk.


Corresponding author

Address for correspondence: Dr Shankai Yin, The Affiliated Sixth People's Hospital, Otolaryngology Institute of Shanghai Jiao Tong University, 600 Yishan Road, Shanghai 200233, China Fax: +86 21 64834143 E-mail:


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1Young, T, Peppard, PE, Gottlieb, DJ. Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med 2002;165:1217–39
2West, SD, Nicoll, DJ, Stradling, JR. Prevalence of obstructive sleep apnea in men with type 2 diabetes. Thorax 2006;61:945–50
3Vgontzas, AN, Bixler, EO, Chrousos, GP. Sleep apnea is a manifestation of the metabolic syndrome. Sleep Med Rev 2005;9:211–24
4Hoffstein, V, Mateika, S. Differences in abdominal and neck circumferences in patients with and without sleep apnoea. Eur Respir J 1992;5:377–81
5Suzuki, T, Nakano, H, Maekawa, J, Okamoto, Y, Ohnishi, Y, Yamauchi, M et al. Obstructive sleep apnea and carotid artery intima media thickness. Sleep 2004;27:129–33
6Riha, RL, Brander, P, Vennelle, M, McArdle, N, Kerr, SM, Anderson, NH et al. Tumour necrosis factor-alpha (–308) gene polymorphism in obstructive sleep apnoea–hypopnoea syndrome. Eur Respir J 2005;26:673–8
7Barcela, A, Elorza, MA, Barbe, F, Santos, C, Mayoralas, LR, Agusti, AG. Angiotensin converting enzyme in patients with sleep apnea syndrome: plasma activity and gene polymorphisms. Eur Respir J 2001;17:728–32
8Hanaoka, M, Yu, X, Urushihata, K, Ota, M, Fujimoto, K, Kubo, K. Leptin and leptin receptor gene polymorphisms in obstructive sleep apnea syndrome. Chest 2008;133:7985
9Kaparianos, A, Sampsonas, F, Karkoulias, K, Spiropoulos, K. Obstructive sleep apnea syndrome and genes. Neth J Med 2006;64:280–9
10Ringel, J, Engeli, S, Distler, A, Sharma, AM. Pro12Ala missense mutation of the peroxisome proliferator activated receptor γ and diabetes mellitus. Biochem Biophys Res Commun 1999;254:450–3
11Clement, K, Hercberg, S, Passinge, B, Galan, P, Varroud-Vial, M, Shuldiner, AR et al. The Pro115Gln and Pro12Ala PPARγ gene mutations in obesity and type 2 diabetes. Int J Obes Relat Metab Disord 2000;24:391–3
12Cole, SA, Mitchell, BD, Hsueh, W-C, Pineda, P, Beamer, BA, Shuldiner, AR et al. The Pro12Ala variant of peroxisome proliferator-activated receptor-g 2 (PPAR-g 2) is associated with measures of obesity in Mexican Americans. Int J Obesity 2000;24:522–4
13Masud, S, Ye, S. Effect of the peroxisome proliferator activated receptor-gamma gene Pro12Ala variant on body mass index: a meta analysis. J Med Genet 2003;40:773–80
14Anonymous. The Report of an American Academy of Sleep Medicine Task Force. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep 1999;22:667–89
15Bonora, E, Targher, G, Alberiche, M, Bonadonna, RC, Saggiani, F, Zenere, MB et al. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care 2000;23:5763
16Prasad, KN, Saxena, A, Ghoshal, UC, Bhagat, MR, Krishnani, N. Analysis of Pro12Ala PPAR gamma polymorphism and Helicobacter pylori infection in gastric adenocarcinoma and peptic ulcer disease. Ann Oncol 2008;19:1299–303
17Swarbrick, MM, Chapman, CM, McQuillan, BM, Hung, J, Thompson, PL, Beilby, JP. A Pro12Ala polymorphism in the human peroxisome proliferator-activated receptor-gamma 2 is associated with combined hyperlipidaemia in obesity. Eur J Endocrinol 2001;144:277–82
18Lehrke, M, Lazar, MA. The many faces of PPAR gamma. Cell 2005;123:993–99
19Evans, RM, Barish, GD, Wang, YX. PPARs and the complex journey to obesity. Nat Med 2004;10:355–61
20Deeb, SS, Fajas, L, Nemoto, M, Pihlajamäki, J, Mykkänen, L, Kuusisto, J et al. A Pro12Ala substitution in PPAR gamma-2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nature Genet 1998;20:284–7
21Gonzalez, SJL, Serrano, RM, Fernandez, PC, Laakso, M, Martínez Larrad, MT. 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 2002;147:495501
22Tonjes, A, Scholz, M, Loeffler, M, Stumvoll, M. Association of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma with pre-diabetic phenotypes: meta-analysis of 57 studies on nondiabetic individuals. Diabetes Care 2006;29:2489–97
23Beamer, BA, Yen, CJ, Andersen, RE, Muller, D, Elahi, D, Cheskin, LJ et al. Association of the Pro12Ala variant in the peroxisome proliferator-activated receptor-gamma2 gene with obesity in two Caucasian populations. Diabetes 1998;47:1806–8



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