Genetic aspects of metabolic disorders in pregnant women with pathological weight gain

  • S. O. Ostafiichuk Ivano-Frankivsk National Medical University
Keywords: LEPR Gln233Arg polymorphism; leptin; lipid profile; carbohydrate status; insulin resistance.


Polymorphism of the leptin receptor gene (LEPR) has been shown to be linked to obesity-related metabolic markers and phenotype. Therefore, we hypothesized that the Gln233Arg LEPR polymorphism is related to metabolic changes in pregnancy and the risk of excessive gestational weight gain (GWG). A total of 97 pregnant women with a singleton gestation were enrolled from April 2016 until December 2018. Genetic variants of LEPR were analyzed by real-time polymerase chain reaction, leptin by enzyme-linked immunosorbent assay, lipid profile, and carbohydrate status were assessed in the first, and third trimesters of pregnancy. The recommended GWG was diagnosed in 34.0%, insufficient in 19.6%, and excessive in 46.4% patients. Statistical analysis revealed that 20.6% patients were with AA genotype, 50.5% – AG genotype, and 28.9% – GG genotype. The frequency of GG-alleles carriers of the LEPR Gln233Arg gene in the group of excessive GWG patients was 3 times higher compared to recommended GWG patients. Thus, the inheritance of pathological G-homozygotes increases the risk of excessive weight gain by 7 times, compared to carriers of the AA genotype. LEPR GG polymorphism was significantly associated with high levels of triglycerides, total cholesterol, lipoprotein low and very low density, and leptin compared to homozygous А-carriers in the third trimester of pregnancy. In pregnant women with GG polymorphism, the glucose level, insulin level, and HOMO-IR index were significantly increased compared to women with AA genotype in late pregnancy. In the group with excessive GWG, the presence of GG-alleles of the LEPR gene was accompanied by a higher level of hyperleptinemia, compared to carriers of AA-genotype. Inheritance of pathological G-homozygotes was associated with hyperlipidemia, leptin resistance with high leptin serum levels, and increased insulin resistance, which was especially manifested in excessive GWG. In our opinion, excessive GWG can be seen as a marker of the mother's genotype and genetic predisposition to the development of metabolic diseases after delivery.


Berglund, E. D., Vianna, C. R., Donato, J., Kim, M. H., Chuang, J. C., Lee, C. E., Lauzon, D. A., Lin, P., Brule, L. J., & Scott, M. M. (2012). Direct leptin action on POMC neurons regulates glucose homeostasis and hepatic insulin sensitivity in mice. Journal of Clinical Investigation, 122, 1000–1009.

Costa, M. A. (2016). The endocrine function of human placenta: An overview. Reproductive Biomedicine Online, 32(1), 14–43.

Daghestani, M., Purohit, R., Daghestani, M., Daghistani, M., & Warsy, A. (2019). Molecular dynamic (MD) studies on Gln233Arg (rs1137101) polymorphism of leptin receptor gene and associated variations in the anthropometric and metabolic profiles of Saudi women. PLoS One, 14(2), e0211381.

Dereń, K., Nyankovskyy, S., Nyankovska, O., Łuszczki, E., Wyszyńska, J., Sobolewski, M., & Mazur, A. (2018). The prevalence of underweight, overweight and obesity in children and adolescents from Ukraine. Scientific Reports, 8, e3625.

Devlieger, R., Benhalima, K., Damm, P., Van Assche, A., Mathieu, C., Mahmood, T., Dunne, F., & Bogaerts, A. (2016). Maternal obesity in Europe: Where do we stand and how to move forward? European Journal of Obstetrics and Gynecology and Reproductive Biology, 201, 203–208.

Farpour-Lambert, N. J., Louisa, J. E., Martinez de Tejada, B., & Scott, C. (2018). Obesity and weight gain in pregnancy and postpartum: An evidence review of lifestyle interventions to inform maternal and child health policies. Frontiers in Endocrinology (Lausanne), 9, 546–552.

Farzam, F., Mahmazi, S., & Nasseryan, J. (2017). Association of leptin receptor gene Gln223Arg and lys109Arg polymorphisms with obesity and overweight in an iranian young population. Gene Cell Tissue, 4(3), e57937.

Ghali, Z. H., Ahmed, I. H., Gorshunska, M. Y., Pоchеrnyaev, A. K., & Atramentova, L. A. (2012). Structure of Ukrainian population on SNP rs1137101 of leptin receptor gene LEPR. Visnyk of V. N. Karazin Kharkiv National University, Biology, 15, 94–98.

Goldstein, R. F., Abell, S. K., Ranasinha, S., Misso, M. L., Boyle, J. A., Harrison, C. L., Black, M. H., Li, N., Hu, G., Corrado, F., Hegaard, H., Kim, Y. J., Haugen, M., Song, W. O., Kim, M. H., Bogaerts, A., Devlieger, R., Chung, J. H., & Teede, H. J. (2018). Gestational weight gain across continents and ethnicity: Systematic review and meta-analysis of maternal and infant outcomes in more than one million women. BMC Medicine, 16(1), 153–167.

Hales, C. M., Carroll, M. D., Fryar, C. D., & Ogden, C. L. (2017). Prevalence of obesity among adults and youth: United States, 2015–2016. NCHS Data Brief, 288, 1–8.

Jing, X., Ou, C., Chen, H., Wang, T., Xu, B., Lu, S., & Zhu, B. (2016). Electroacupuncture reduces weight gain induced by rosiglitazone through PPARgamma and leptin receptor in CNS. Evidence – Based Complementary and Alternative Medicine, 2, 1–12.

Li, Y. Y., Wang, H., Yang, X. X., Wu, J. J., Geng, H. Y., Kim, H. J., Yang, Z. J., & Wang, L. S. (2017). LEPR gene Gln223Arg polymorphism and type 2 diabetes mellitus: A meta – analysis of 3,367 subjects. Oncotarget, 37(8), e61927.

Logan, C. A., Bornemann, R., Koenig, W., Reister, F., Walter, V., Fantuzzi, G., Weyermann, M., Brenner, H., Genuneit, J., & Rothenbacher, D. (2017). Gestational weight gain and fetal-maternal adiponectin, leptin, and CRP: Results of two birth cohorts studies. Scientific Reports, 2(7), e41847.

Lopez, M. (2016). Hypothalamic leptin resistance: From BBB to BBSome. PLoS Genetics, 12(5), e1005980.

Mahmoudi, R., & Alavicheh, B. N. (2015). Polymorphisms of leptin (2548 G/A) and leptin receptor (Q223R) genes in iranian women with breast cancer. International Journal of Genomics, 6, e132720.

Manriquez, V., Aviles, J., Salazar, L., Saavedra, N., Seron, P., Lanas, F., Fajardo, C. M., Hirata, M. H., Hirata, R. D. C., & Cerda, A. (2018). Polymorphisms in genes involved in the leptin-melanocortin pathway are associated with obesity-related cardiometabolic alterations in a Southern Chilean population. Molecular Diagnosis and Therapy, 22(1), 101–113.

Maymó, J. L., Pérez Pérez, A., Gambino, Y., Calvo, J. C., Sánchez-Margalet, V., & Varone, C. L. (2011). Review: Leptin gene expression in the placenta-regulation of a key hormone in trophoblast proliferation and survival. Placenta, 32(2), 146–153.

Napso, T., Yong, H. E. J., Lopez-Tello, J., & Sferruzzi-Perri, A. N. (2018). The role of placental hormones in mediating maternal adaptations to support pregnancy and lactation. Frontiers in Physiology, 9, e1091.

Olza, J., Rupérez, A. I., Gil-Campos, M., Leis, R., Cañete, R., Tojo, R. Á., & Aguilera, M. (2017). Leptin receptor gene variant rs11804091 is associated with BMI and insulin resistance in Spanish female obese children: A case-control study. International Journal of Molecular Sciences, 18(8), e1690.

Paz-Fhilo, G., Mastronardi, C., & Franco, C. (2012). Leptin: Molecular mechanisms, systemic pro-inflammatory effects, and clinical implications. Arquivos Brasileiros de Endocrinologia and Metabologia, 56, 597–607.

Pérez-Pérez, A., Toro, A., Vilariño-Garcia, T., Guadix, P., Maymó, J., Dueñas, J. L., Varone, C., & Sánchez-Margalet, V. (2019). Leptin protects placental cells from apoptosis induced by acidic stress. Cell and Tissue Research, 375, 733–742.

Sámano, R., Martínez-Rojano, H., Chico-Barba, G., Godínez-Martínez, E., Sánchez-Jiménez, B., Montiel-Ojeda, D., & Tolentino, M. (2017). Serum concentration of leptin in pregnant adolescents correlated with gestational weight gain, postpartum weight retention and newborn weight/length. Nutrients, 9(10), e1067.

Sara, C., Bladh, M., Brynhildsen, J., Claesson, I.-M., Josefsson, A., Sydsjö, G., Thorsell, A., & Blomberg, M. (2016). Maternal obesity (Class I-III), gestational weight gain and maternal leptin levels during and after pregnancy: A prospective cohort study. BMC Obesity, 3, 28–38.

Sulaieva, O., Belemets, N., Goncharov, S., & Dosenko, V. (2018). Gender differences in the relation between Q223R polymorphism of leptin receptor gene and risk of type 2 diabetes mellitus. Clinical Endocrinology and Endocrine Surgery, 64(4), 29–34 (in Ukrainian).

Sulaieva, O., Chereshneva, Y., Kartashkina, N., Ivanova, M., & Tsomartova, D. (2018). Secretory function of white adipose tissue and adipokines: Biological effects and clinical significance. Georgian Med News, 274, 116–124 (in Russian).

Suriyaprom, K., Tungtrongchitr, R., & Thawnasom, K. (2014). Measurement of the levels of leptin, BDNF associated with polymorphisms LEP G2548A, LEPR Gln223Arg and BDNF Val66Met in Thai with metabolic syndrome. Diabetology and Metabolic Syndrome, 6, 6–13.

Tessier, D. R., Ferraro, Z. M., & Gruslin, A. (2013). Role of leptin in pregnancy: Consequences of maternal obesity. Placenta, 34(3), 205–211.

Tsai, P-J. S., Davis, J., & Bryant-Greenwood, G. (2015). Systemic and placental leptin and its receptors in pregnancies associated with obesity. Reproductive Sciences, 22(2), 189–197.

Yang, Y., & Niu, T. (2018). A meta-analysis of associations of LEPR Q223R and K109R polymorphisms with type 2 diabetes risk. PLoS One, 13(1), e0189366.

How to Cite
Ostafiichuk, S. O. (2019). Genetic aspects of metabolic disorders in pregnant women with pathological weight gain . Regulatory Mechanisms in Biosystems, 10(3), 271-275.