Assessment of association between the Pro12Ala polymorphism of PPAR-γ gene with the risk of obstetric complications

Authors

  • S. O. Ostafiichuk Ivano-Frankivsk National Medical University, Ukraine,

DOI:

https://doi.org/10.14739/2310-1210.2019.5.179431

Keywords:

Pro12Ala polymorphism of PPAR-γ gene, weight gain, placental insufficiency, postpartum period

Abstract

 

Aim – to determine the association between Pro12Ala polymorphism of PPAR-γ gene with the risk of obstetric complications.

Materials and methods. A total of 97 women with normal prepregnancy weight, singleton pregnancy, delivery at 37 weeks or more and without chronic diseases with follow-up of pregnancy and 1 year after delivery at antenatal clinics. Anthropometry, determination of body fat percentage (BF %) by spectral bioimpedansometry method, Pro12Ala polymorphism of the PPAR-γ gene using the polymerase chain reaction were performed. Statistical analyses were carried out using Microsoft Excel-based statistical analysis package.

Results. Gestational weight gain (GWG) was diagnosed 1.6 times higher in women with PPAR-γ Pro12Ala polymorphism, than in those with the Pro/Pro genotype (P < 0.05). In the group of women with an excessive weight gain, the number of Ala-allele carriers was 2.6 times (OR 3.2, 95 % CI 1.1–9.3, P < 0.05) higher than among subjects with recommended weight gain. PPAR-γ Ala12 carriers had 1.3 times greater BF % compared to homozygous Pro-carriers (P < 0.05). One year postpartum, Ala12-allele patients had body weight and body mass index (BMI) 1.3 (P < 0.05) and 1.2 (P < 0.05) times higher, respectively, compared to Pro/Pro genotype women. The presence of Pro12Ala polymorphism 1.8 times (OR 3.1; 95% CI 1.3–7.7; P < 0.05) increased the risk of postpartum weight retention. It has been found, that in women with Pro12Ala polymorphism of PPAR-γ gene, the risk of preterm delivery was increased by 2.7 times (OR 3.7, 95 % CI, 1.3–10.5, P < 0.05), placental dysfunction – by 2.1 times (OR 3.6, 95 % CI 1.4–9.4, P < 0.05), intrauterine growth retardation (IUGR) – by 2.7 times (OR 3.7, 95 % CI 1.3–10.5, P < 0.05), preeclampsia – by 2.0 times (OR 2.9; 95% CI 1.1–7.2, P < 0.05), polyhydramnios – by 3,3 times (OR 4.2, 95 % CI, 1.3–13.5, P < 0.05), oligohydramnios – by 2.8 times (OR 3.5, 95 % CI, 1.1–11.0, P < 0.05) as compared to Pro/Pro genotype carriers.

Conclusions. The failure of metabolic and angiogenic adaptive processes during pregnancy with proven altered gene potential, can serve as a biological marker for the mother's genotype and an increased risk of genetic predisposition to metabolic and cardiovascular diseases development after delivery.

 

References

Ji, L., Brkić, J., Liu, M., Fu, G., Peng, C., & Wang, Y. L. (2013). Placental trophoblast cell differentiation: Physiological regulation and pathological relevance to preeclampsia. Molecular Aspects of Medicine, 34(5), 981–1023. doi: 10.1016 /j.mam.2012.12.008

Zeisler, H., Llurba, E., Chantraine, F., Vatish, M., Staff, A. C., Sennström, M., et al. (2016). Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia. N Engl J Med, 374(1), 13–22. doi: 10.1056/NEJMoa1414838

Clifton, V. L., Stark, M. J., Osei-Kumah, A., & Hodyl, N. A. (2012). Review: The feto-placental,unit, pregnancy pathology and impact on long term maternal health. Placenta, 33, Suppl: S37–41. doi: 10.1016/j.placenta.2011.11.005

McCarthy, F. P., Drewlo, S., English, F. A., Kingdom, J., Johns, E. J., Kenny, L. C., & Walsh, S. K. (2011). Evidence implicating peroxisome proliferator-activated receptor-g in the pathogenesis of preeclampsia. Hypertension, 58(5), 882–887. doi: 10.1161/ HYPERTENSIONAHA.111.179440

Zeisler, H., Llurba, E., Chantraine, F. J., Vatish, M., Staff, A. C., Sennström, M., et al. (2018). The sFlt-1/PlGF Ratio: ruling out pre-eclampsia for up to 4 weeks and the value of retesting: sFlt-1/PlGF ratio to rule out pre-eclampsia. Ultras Obstet Gynecol., 53(3). doi: 10.1002/ uog.19178

Peeters, L. L., Vigne, J. L., Tee, M. K., Zhao, D., Waite, L. L., & Taylor, R. N. (2005). PPARgamma represses VEGF expression in human endometrial cells: implications for uterine angiogenesis. Angiogenesis, 8(4), 373–379. doi: 10.1007/s10456-005-9027-4

Fournier, T., Guibourdenche, J., Handschuh, K., Tsatsaris, V., Rauwel, B., Davrinche, C., & Evain-Brion, D. (2011). PPARg and human trophoblast differentiation. J Reprod Immunol, 90(1), 41–49. doi: 10.1016/j.jri.2011.05.003

Kadam, L., Kohan-Ghadr, R., & Drewlo, H. S. (2015). The balancing act – PPAR-c’s roles at the maternal-fetal interface. Syst Biol Reprod Med, 61(2), 65–71. doi: 10.3109/ 19396368.2014.991881

Corrales, P., Vidal-Puig, A., & Medina-Gómez, G. (2018). PPARs and Metabolic Disorders Associated with Challenged Adipose Tissue Plasticity. Int J Mol Sci, 19(7), 2124. doi: 10.3390/ijms19072124

McCarthy, F. P., Delany, A. C., Kenny, L. C., & Walsh, S. K. (2013). PPAR-γ - a possible drug target for complicated pregnancies. Br J Pharmacol, 168(5), 1074–1085. doi: 10.1111/bph.12069

Gao, Y., She, R., & Sha, W. (2017). Gestational diabetes mellitus is associated with decreased adipose and placenta peroxisome proliferator-activator receptor expression in a Chinese population. Oncotarget, 8(69), 113928–113937. doi: 10.18632/oncotarget.23043

McCarthy, F. P, Drewlo, S., Kingdom, J., Johns, E. J., Walsh, S. K, & Kenny, L. C. (2011). Peroxisome proliferator-activated receptorgamma as a potential therapeutic target in the treatment of preeclampsia. Hypertension, 58(2), 280–286. doi: 110.1161/HYPERTENSIONAHA.111.172627

Laasanen, J., Heinonen, S., Hiltunen, M., Mannermaa, A. & Laakso, M. (2002). Polymorphism in the peroxisome proliferator-activated receptor-γ gene in women with preeclampsia. Early Hum Develop, 69(1-2), 77–82. doi: 10.1016/S0378-3782(02)00069-5

Stuebe, A. M., Lyon, H., Herring, A. H., Ghosh, J., Wise, A., North, K. E., & Siega-Riz, A.M. (2010). Obesity and diabetes genetic variants associated with gestational weight gain. Am J Obstet Gynecol, 203(3). doi: 10.1016/j.ajog.2010.06.069

Chavan, N. R., 603: PPARG expression varies with excess gestational weight gain (GWG) in pregnancy: An important target in developmental programming. Am J Obstet Gynecol Suppl, 218 (1), 360. doi: 10.1016/ j.ajog.2017.11.131

Kolapo, M. A., Emily, J. A., & Shawn, S. D. (2016). Excessive gestational calorie intake in sows regulates early postnatal adipose tissue development in the offspring. BMC Nutrition, 2, 29. doi: 10.1186/s40795-016-0069-3

Dubossarskaya, Z. M. & Duka Y. M. (2014). Kharakterystyka pokaznykiv vuhlevodnoho obminu u vahitnykh z ozhyrinniam [The characteristic of indicators of the carbohydrate exchange at pregnant women with obesity]. Zdorov'e zhenshchiny, 9(95), 113–115. [in Ukrainian].

Becer, E., & Çırakoğlu, A. (2017). Effect of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ2 gene on lipid profile and gene of lipid and adipokines levels in obese subjects. BJMG, 20(1), 71–80. doi: 10.1515/bjmg-2017-0007

Institute of Medicine and National Research Council of the National Academies, Committee to Reexamine IOM Pregnancy Weight Guidelines, Food and Nutrition Board on Children, Youth, and Families (2009). IOM, Weight Gain During Pregnancy: Reexamining the Guidelines. Washington, D.C.: The National Academies Press.

(2011) Nakaz Ministerstva okhorony zdorovia Ukrainy «Metodychni rekomendatsii shchodo orhanizatsii ambulatornoi akushersko-hinekolohichnoi dopomohy» vid 15.07.2011 r. №417 [Order of the Ministry of Health of Ukraine «Methodological recommendations for the organization of ambulatory obstetric and gynecological care » from July 15, 2011 №417]. Kyiv. [in Ukrainian].

Staelens, A. S., Vonck, S., Molenberghs, G., Malbrain, M. L., & Gyselaers, W. (2016). Maternal body fluid composition in uncomplicated pregnancies and preeclampsia: a bioelectrical impedance analysis. The European J of Obstet & Gynecol and Reprod Biol, 204, 69–73. doi: 10.1016/j.ejogrb.2016.07.502

Jeon, C., Chang, S. C., Mu, L., Zhao, J., Rao, J. Y., Lu, Q. Y., & Zhang, Z. F. (2013). Genetic variants of peroxisome proliferator-activated receptor δ are associated with gastric cancer. Dig Dis Sci, 58(10), 2881–2887. doi: 10.1007/s10620-013-2770-2

Meirhaeghe, A., & Amouyel, P. (2004). Impact of genetic variation of PPAR gamma in humans. Mol Genet Metab, 83(1–2), 93–102. doi: 10.1016/ j.ymgme.2004.08.014

Zera, C. A., Seely, E. W., Wilkins-Haug, L. E., Lim, K. H., Parry, S. I., & McElrath, T. F. (2014). The association of body mass index with serum angiogenic markers in normal and abnormal pregnancies. Am J Obstet Gynecol, 211(3), 247.e1-7. doi: 10.1016/j.ajog. 2014.03.020

Baumfeld, Y., Herskovitz, R., Niv, Z. B., Mastrolia, S. A., & Weintraub, A. Y. (2017). Placenta associated pregnancy complications in pregnancies complicated with placenta previa. Taiwan J Obstet Gynecol, 56(3), 331–335. doi: 10.1016/j.tjog. 2017.04.012

Vivas, Y., Díez-Hochleitner, M., Izquierdo-Lahuerta, A., Corrales, P., Horrillo, D., Velasco, I., et al. (2016). Peroxisome Proliferator-Activated Receptor-2 Modulates Late-Pregnancy Homeostatic Metabolic Adaptations. Mol Med, 22, 724–736. doi: 10.2119/molmed.2015.00262

Svensson, H., Wetterling, L., Bosaeus, M., Odén, B., Odén, A., Jennische, E., et al. (2016). Body fat mass and the proportion of very large adipocytes in pregnant women are associated with gestational insulin resistance. Int. J. Obes. (Lond), 40(4), 646–653. doi: 10.1038/ ijo.2015.232

Mansoori, A., Amini, M., Kolahdooz, F., & Seyedrezazadeh, E. (2015). Obesity and Pro12Ala Polymorphism of Peroxisome Proliferator-Activated Receptor-Gamma Gene in Healthy Adults: A Systematic Review and Meta-Analysis. Ann Nutr Metab, 67(2), 104–118. doi: 10.1159/000439285

Liu, L., Zhuang, X., Jiang, M., Guan, F., Fu, Q., & Lin, J. (2017). ANGPTL4 mediates the protective role of PPAR activators in the pathogenesis of preeclampsia. Cell Death Dis, 8(9), e3054. doi: 10.1038/cddis.2017.419

Jim, B., & Karumanchi, S. A. (2017). Preeclampsia: Pathogenesis, Prevention, and Long-Term Complications. Seminars Nephrology, 37(4), 386–397. doi: 10.1016/j.semnephrol.2017.05.011

Downloads

How to Cite

1.
Ostafiichuk SO. Assessment of association between the Pro12Ala polymorphism of PPAR-γ gene with the risk of obstetric complications. Zaporozhye Medical Journal [Internet]. 2019Oct.1 [cited 2024Dec.24];(5). Available from: http://zmj.zsmu.edu.ua/article/view/179431

Issue

No. 5 (2019)

Section

Original research

License

Authors who publish with this journal agree to the following terms:

    1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.  Лицензия Creative Commons
    2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
    3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)