Association of the Pro12Ala Polymorphism with the Metabolic Parameters in Women with Polycystic Ovary Syndrome

Authors

  • Moushira Zaki Biological Anthropology Department, National Research Centre, Cairo
  • Naglaa Hassan Biological Anthropology Department, National Research Centre, Cairo
  • Hala T. El-Bassyouni Clinical Genetics Department, National Research Centre, Cairo
  • Sanaa Kamal Biological Anthropology Department, National Research Centre, Cairo
  • Walaa Basha Biological Anthropology Department, National Research Centre, Cairo
  • Osama Azmy Reproductive Health Research Department, National Research Centre, Cairo
  • Khalda Amr Molecular Genetics Department, National Research Centre, Cairo

DOI:

https://doi.org/10.3889/oamjms.2017.088

Keywords:

PCOS, metabolic, parameters, PPARG, polymorphism

Abstract

AIM: To investigate the association of peroxisome proliferator-activated receptor gamma (PPARG) Pro12Ala polymorphism with polycystic ovary syndrome (PCOS) and its effect on the metabolic parameters in PCOS women.

METHODS: The study used PCR to identify the presence of the PPARG Pro12Ala polymorphism in 100 PCOS women and 120 age-matched healthy women. All participants were subjected to anthropometry, biochemical and metabolic evaluation.

RESULTS: Significant difference in the genotypes distributions of PPARG Pro12Ala polymorphism was observed among PCOS women and controls (p = 0.03). The frequency of the polymorphic allele Ala was significantly higher in PCOS cases than that in the controls (OR = 2.01, p = 0.01). The carries of the variant allele Ala in PCOS women showed significant higher values in body mass index (BMI), systolic and diastolic blood pressure, waist circumference, waist to hip ratio, sum of skin folds, fasting blood glucose, fasting blood insulin, HOMA-IR, fasting triglycerides, total cholesterol and low-density lipoprotein than non-carriers.

CONCLUSION: The PPARG Pro12Ala polymorphism might contribute to the risk of PCOS and abnormal metabolic parameters and could be considered as a biomarker for early diagnosis and clinic prediction of metabolic complications.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Auwerx, J. PPARγ, the ultimate thrifty gene. Diabetologia. 1999; 42(9):1033-1049. https://doi.org/10.1007/s001250051268 PMid:10447513

He J, Wang L, Liu J, Liu F, Li X. A meta-analysis on the association between PPAR-γ Pro12Ala polymorphism and polycystic ovary syndrome. J Assist Reprod Genet. 2012; 29(7): 669-77. https://doi.org/10.1007/s10815-012-9772-4 PMid:22527903 PMCid:PMC3401263

Hart R, Hickey M, Franks S. Definitions, prevalence and symptoms of polycystic ovaries and polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol. 2004; 18:671–83. https://doi.org/10.1016/j.bpobgyn.2004.05.001 PMid:15380140

Farrell K, Antoni MH. Insulin resistance, obesity, inflammation, and depression in polycystic ovary syndrome: behavioral mechanisms and interventions. Fertil Steril. 2010; 94:1565–1574. https://doi.org/10.1016/j.fertnstert.2010.03.081 PMid:20471009 PMCid:PMC2941530

Tatemoto K, Hosoya M, Habata Y, et al. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun. 1998; 251:471–476. https://doi.org/10.1006/bbrc.1998.9489 PMid:9792798

Wojciechowski P, Lipowska A, Rys P, et al. Impact of FTO genotypes on BMI and weight in polycystic ovary syndrome: a systematic review and meta-analysis. Diabetologia. 2012; 55:2636–2645. https://doi.org/10.1007/s00125-012-2638-6 PMid:22801903 PMCid:PMC3433670

Hosoya M, Kawamata Y, Fukusumi S, et al. Molecular and functional characteristics of APJ. Tissue distribution of mRNA and interaction with the endogenous ligand apelin. J Biol Chem. 2000; 275: 21061–2167. https://doi.org/10.1074/jbc.M908417199 PMid:10777510

Falca˜o-Pires I, Gonc¸alves N, Henriques-Coelho T, Moreira-Gonc¸alves D, Roncon-Albuquerque Jr R, Leite-Moreira AF. Apelin decreases myocardial injury and improves right ventricular function in monocrotaline-induced pulmonary hypertension. Am J Physiol Heart Circ Physiol. 2009; 296: H2007–20014. https://doi.org/10.1152/ajpheart.00089.2009 PMid:19346461

Reyss AC, Proust-Richard C, Catteau-Jonard S, Dewailly D. [Rotterdam consensus in adolescent girls: which investigations and how to interpret them to make the diagnosis of PCOS?]. Gynecol Obstet Fertil. 2006;34(4):341-6. https://doi.org/10.1016/j.gyobfe.2006.02.017 PMid:16630737

Yilmaz M, Ergun MA, Karakoc A, et al. Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-c gene in women with polycystic ovary syndrome. Gynecol Endocrinol. 2006;22: 336–342. https://doi.org/10.1080/09513590600733357 PMid:16785159

Hiernaux J, Tanner JM. Growth and Physical Studies. In: Human Biology: A Guid to field Methods, Weiner JS and Lourie SA (EDs.). Blackwell scientific Publications, London: Oxford, 1969. PMid:5403554

Hirschler V, Molinari C, Beccaria M, Maccallini G, Aranda C. Comparison of various maternal anthropometric indices of obesity for identifying metabolic syndrome in offspring. Diabetes Technol Ther. 2010; 12(4):297-305. https://doi.org/10.1089/dia.2009.0164 PMid:20210569

Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972; 18(6):499-502. PMid:4337382

Chu YL, Qiu HY, Sun YY, Li M, Li HF. Detection and significance of phosphatidylinositol 3-kinase in adipose tissue of polycystic ovary syndrome patients with insulin resistance. Zhonghua Fu Chan Ke Za Zhi. 2006; 41(7):455-458. PMid:17083810

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(7): 412-419. https://doi.org/10.1007/BF00280883 PMid:3899825

Baldani DP, Skrgatic L, Cerne JZ, Ferk P, Simunic V, Gersak K. Association of PPARG Pro12Ala polymorphism with insulin sensitivity and body mass index in patients with polycystic ovary syndrome. Biomed Rep. 2014; 2(2): 199–206. PMid:24649096

Shaikh N, Mukherjee A, Shah N, Meherji P, Mukherjee S. Peroxisome proliferator activated receptor gamma gene variants influence susceptibility and insulin related traits in Indian women with polycystic ovary syndrome. J Assist Reprod Genet. 2013; 30(7): 913-921. https://doi.org/10.1007/s10815-013-0025-y PMid:23748472 PMCid:PMC3725223

Hara M, Alcoser SY, Qaadir A, Beiswenger KK, Cox NJ and Ehrmann DA. Insulin resistance is attenuated in women with poly¬cystic ovary syndrome with the Pro(12)Ala polymorphism in the PPARgamma gene. J Clin Endocrinol Metab. 2002; 87: 772 775. PMid:11836319

Korhonen S, Heinonen S, Hiltunen M, et al. Polymorphism in the peroxisome proliferator activated receptor gamma gene in women with polycystic ovary syndrome. Hum Reprod. 2003; 18: 540 543. https://doi.org/10.1093/humrep/deg128 PMid:12615821

Dokras A, Sarwer DB, Allison KC, Milman L, Kris-Etherton PM, Kunselman AR, Stetter CM, Williams NI, Gnatuk CL, Estes SJ, Fleming J, Coutifaris C, Legro RS. Weight Loss and Lowering Androgens Predict Improvements in Health-Related Quality of Life in Women with PCOS. J Clin Endocrinol Metab. 2016; 101(8): 2966-2974. https://doi.org/10.1210/jc.2016-1896 PMid:27253669

Kim KS, Choi SM, Shin SU, Yang HS and Yoon Y. Effects of peroxisome proliferator-activated receptor-γ2 Pro12Ala polymorphism on body fat distribution in female Korean subjects. Me-tabolism. 2004; 53: 1538-1543. https://doi.org/10.1016/j.metabol.2004.06.019

Tőnjes 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; 29:2489–297. https://doi.org/10.2337/dc06-0513 PMid:17065690

Masud S, Ye S and SAS Group. Effect of the peroxisome prolif¬erator activated receptor gamma gene Pro12Ala variant on body mass index: a meta analysis. J Med Genet. 2003; 40: 773 780. https://doi.org/10.1136/jmg.40.10.773 PMid:14569127 PMCid:PMC1735275

Christopoulos P, Mastorakos G, Gazouli M, et al. Peroxisome proliferator activated receptor gamma and delta polymor¬phisms in women with polycystic ovary syndrome. Ann NY Acad Sci. 2010; 1205: 185 191. https://doi.org/10.1111/j.1749-6632.2010.05647.x PMid:20840271

Koika V, Marioli DJ, Saltamavros AD, et al. Association of the Pro12Ala polymorphism in peroxisome proliferator activated receptor gamma2 with decreased basic metabolic rate in women with polycystic ovary syndrome. Eur J Endocrinol. 2009; 161: 317 322. https://doi.org/10.1530/EJE-08-1014 PMid:19465486

Orio F Jr, Palomba S, Cascella T, et al. Lack of an association between peroxisome proliferator activated receptor gamma gene Pro12Ala polymorphism and adiponectin levels in the polycystic ovary syndrome. J Clin Endocrinol Metab. 2004; 89:5110–5115. https://doi.org/10.1210/jc.2004-0109 PMid:15472214

Antoine HJ, Pall M, Trader BC, Chen YD, Azziz R and Goodarzi MO. Genetic variants in peroxisome prolif¬erator activated receptor gamma influence insulin resistance and testosterone levels in normal women, but not those with poly¬cystic ovary syndrome. Fertil Steril. 2007; 87: 862 869. https://doi.org/10.1016/j.fertnstert.2006.10.006 PMid:17141766 PMCid:PMC1925257

Zhang J, Fu M, Cui T, et al. Selective disruption of PPARgamma 2 impairs the development of adipose tissue and insulin sensitivity. Proc Natl Acad Sci USA. 2004; 101: 10703 10708. https://doi.org/10.1073/pnas.0403652101 PMid:15249658 PMCid:PMC489998

San Millan JL, Escobar Morreale HF. The role of genetic variation in peroxisome proliferator activated receptors in the polycystic ovary syndrome (PCOS): an original case control study followed by systematic review and meta-analysis of existing evidence. Clin Endocrinol (Oxf). 2010; 72: 383 392. https://doi.org/10.1111/j.1365-2265.2009.03679.x PMid:19681917

Dragojevic J, Ostanek B, Mencej Bedrac S, Komadina R, Prezelj J, Marc J. PPARG gene promoter polymorphism is associated with non-traumatic hip fracture risk in the elderly Slovenian population: a pilot study. Clin Biochem. 2011; 44:1085- 1089. https://doi.org/10.1016/j.clinbiochem.2011.06.981 PMid:21756892

Orio F Jr, Matarese G, Di Biase S, et al (2003). Exon 6 and 2 peroxisome proliferator activated receptor gamma polymorphisms in polycystic ovary syndrome. J Clin Endocrinol Metab. 2003; 88: 5887 5892. https://doi.org/10.1210/jc.2002-021816 PMid:14671186

Xita N, Lazaros L, Georgiou I and Tsatsoulis A. The Pro12Ala polymorphism of the PPAR gamma gene is not associated with the polycystic ovary syndrome. Hormones (Athens). 2009; 8: 267 272.

Lehrke M and Lazar MA. The many faces of PPAR gamma. Cell. 2005; 123: 993-999. https://doi.org/10.1016/j.cell.2005.11.026 PMid:16360030

Luan J, Browne PO, Harding AH, et al. Evidence for gene nutrient interaction at the PPARgamma locus. Diabetes. 2001; 50: 686 689. https://doi.org/10.2337/diabetes.50.3.686 PMid:11246892

Wijeyaratne CN, Balen AH, Barth JH, Belchetz PE. Clinical manifestations and insulin resistance (IR) in polycystic ovary syndrome (PCOS) among South Asians and Caucasians: is there a difference? Clin Endocrinol (Oxf). 2002; 57:343–50. https://doi.org/10.1046/j.1365-2265.2002.01603.x

Palep-Singh M, Picton HM, Vrotsou K, Maruthini D, Balen AH. South Asian women with polycystic ovary syndrome exhibit greater sensitivity to gonadotropin stimulation with reduced fertilization and ongoing pregnancy rates than their Caucasian counterparts. Eur J Obstet Gynecol Reprod Biol. 2007; 134:202–7. https://doi.org/10.1016/j.ejogrb.2007.02.005 PMid:17367914

Palep-Singh M, Picton H M, Yates Z R, Barth, J, & Balen A H. Polycystic ovary syndrome and the single nucleotide polymorphisms of methylenetetrahydrofolate reductase: a pilot observational study. Human Fertility. 2007; 10(1), 33-41. https://doi.org/10.1080/14647270600950157 PMid:17454207

Glintborg D, Mumm H, Hougaard D, Ravn P, Andersen M. Ethnic differences in Rotterdam criteria and metabolic risk factors in a multiethnic group of women with PCOS studied in Denmark. Clin Endocrinol (Oxf). 2010; 73:732–8. https://doi.org/10.1111/j.1365-2265.2010.03873.x PMid:20846294

Deeb SS, Fajas L, Nemoto M, et al. A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet. 1998; 20: 284 287. https://doi.org/10.1038/3099 PMid:9806549

Ek J, Urhammer SA, Sorensen TI, Andersen T, Auwerx J and Pedersen O. Homozygosity of the Pro12Ala variant of the peroxisome proliferation activated receptor gamma2 (PPAR gamma2): divergent modulating effects on body mass index in obese and lean Caucasian men. Diabetologia. 1999; 42: 892 895. https://doi.org/10.1007/s001250051243 PMid:10440134

Kao WH, Coresh J, Shuldiner AR, et al. Atherosclerosis Risk in Communities Study: Pro12Ala of the peroxisome proliferator activated receptor gamma2 gene is associated with lower serum insulin levels in nonobese African Americans: the Atherosclerosis Risk in Communities Study. Diabetes. 2003; 52: 1568 1572. https://doi.org/10.2337/diabetes.52.6.1568 PMid:12765972

Jaziri R, Lobbens S, Aubert R, et al. DESIR Study Group: The PPARG Pro12Ala polymorphism is associated with a decreased risk of developing hyperglycemia over 6 years and combines with the effect of the APM1 G 11391A single nucleotide polymorphism: the Data From an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study. Diabetes. 2006; 55: 1157 1162. https://doi.org/10.2337/diabetes.55.04.06.db05-0676 PMid:16567542

Published

2017-06-13

How to Cite

1.
Zaki M, Hassan N, El-Bassyouni HT, Kamal S, Basha W, Azmy O, Amr K. Association of the Pro12Ala Polymorphism with the Metabolic Parameters in Women with Polycystic Ovary Syndrome. Open Access Maced J Med Sci [Internet]. 2017 Jun. 13 [cited 2024 Mar. 28];5(3):275-80. Available from: https://oamjms.eu/index.php/mjms/article/view/oamjms.2017.088

Issue

Section

A - Basic Science

Most read articles by the same author(s)