Skip to main content

Advertisement

Log in

Interleukin-17 and leptin genes polymorphisms and their levels in relation to recurrent pregnancy loss in Egyptian females

  • Original Paper
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

Recurrent pregnancy loss (RPL) is a common problem during early gestation. The aim of our study was to investigate the association of IL-17 F( rs763780), IL-17 A ( rs2275913), and leptin (2548 G/A) gene polymorphisms with RPL in obese and lean Egyptian females, and to find out whether these gene polymorphisms affect the women’s serum levels. One hundred and twenty patients with RPL and 120 fertile volunteers with no history of pregnancy loss were genotyped for leptin (2548 G/A), IL-17 A (rs2275913), and IL-17 F (rs763780) polymorphisms by RFLP. The serum level of IL-17 was measured by ELISA, while serum leptin level was measured by HPLC. We found that IL-17 F (rs763780) polymorphism was associated with a decreased risk of RPL in Egyptian females, and we also found that IL-17 A (rs2275913) and LEP (2548 G/A) SNP were associated with an increased risk of RPL. We also demonstrated that both the IL-17 and leptin levels were elevated in the women with RPL and in an obese subgroup within RPL in comparison to a lean one.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Baban RS, Ali NM, Al-Moayed HA (2010) Serum leptin and insulin hormone level in recurrent pregnancy loss. Oman Med J 25(3):203–7

    Article  PubMed Central  PubMed  Google Scholar 

  • Bahadori M, Zarei S, Zarnani AH, Zarei O, Idali F, Hadavi R, Jeddi-Tehrani M (2014) L-6, IL-10 and IL-17 gene polymorphisms in Iranian women with recurrent miscarriage. Iran J Immunol 11(2):97–104

    PubMed  Google Scholar 

  • Bansal AS (2010) Joining the immunological dots in recurrent miscarriage. Am J Reprod Immunol 64(5):307–15

    CAS  PubMed  Google Scholar 

  • Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–5

    Article  CAS  PubMed  Google Scholar 

  • Ben Ali S, Kallel A, Ftouhi B, Sediri Y, Feki M, Slimane H, Jemaa R, Kaabachi N (2009) Association of G-2548A LEP polymorphism with plasma leptin levels in Tunisian obese patients. Clin Biochem 42:584–588

    Article  CAS  PubMed  Google Scholar 

  • Boumaiza I, Omezzine A, Rejeb J, Rebhi L, Ouedrani A, Ben Rejeb N, Nabli N, Ben Abdelaziz A, Bouslama A (2012) Relationship between leptin G2548A and leptin receptor Q223R gene polymorphisms and obesity and metabolic syndrome risk in Tunisian volunteers. Genet Test Mol Biomarkers 16(7):726–33

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chaithra PT, Malini SS, Kumar CS (2011) An overview of genetic and molecular factors responsible for recurrent pregnancy loss. Int J Hum Genet 11(4):217–225

  • Chen H, Chen D-Y, Chen M-J, Chen M-F, Chueh P-J (2009) Decreased ratios of serum Th17/Treg-related cytokines in women with a defect in implantation after in vitro fertilization Formosan. J Rheumatol 23:66–71

    Google Scholar 

  • Chin JR, Heuser CC, Eller AG, Branch DW, Nelson LT, Silver RM (2013) Leptin and leptin receptor polymorphisms and recurrent pregnancy loss. J Perinatol 33:589–592

    Article  CAS  PubMed  Google Scholar 

  • Constantin A, Costache G, Sima AV, Glavce CS, Vladica M, Popov DL (2010) Leptin G-2548A and leptin receptor Q223R gene polymorphisms are not associated with obesity in Romanian subjects. Biochem BiophysRes Commun 391:282–286

    Article  CAS  Google Scholar 

  • Corrêa JD, Madeira MF, Resende RG, Correia-Silva Jde F, Gomez RS, de Souza Dda G, Teixeira MM, Queiroz-Junior CM, da Silva TA(2012) Association between polymorphisms in interleukin-17A and -17F genes and chronic periodontal disease mediators of inflammation. Mediators Inflamm 2012:846052-846061

  • Fan SH, Say YH (2014) Leptin and leptin receptor gene polymorphisms and their association with plasma leptin levels and obesity in a multi-ethnic Malaysian suburban population. J Physiol Anthropol 33:15

    Article  PubMed Central  PubMed  Google Scholar 

  • Franek E, Nowak J, Safranow K, Adler G, Bińczak-Kuleta A, Ciechanowicz A, Wiecek A (2010) G(–2548)A leptin gene polymorphism in obese subjects is associated with serum leptin concentration and bone mass. Pol Arch Med Wewn 120(5):175–180

  • Frieldewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18(6):499–502

    Google Scholar 

  • Furusawa T, Naka I, Yamauchi T, Natsuhara K, Kimura R, Nakazawa M, Ishida T, Inaoka T, Matsumura Y, Ataka Y, Nishida N, Tsuchiya N, Ohtsuka R, Ohashi J (2010) The Q223R polymorphism in LEPR is associated with obesity in Pacific Islanders. Hum Genet 127:287–294

    Article  CAS  PubMed  Google Scholar 

  • Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT (2005) Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6:1123–1132

    Article  CAS  PubMed  Google Scholar 

  • Heikkinen J, Mottonen M, Alanen A, Lassila O (2004) Clin Exp Immunol 136(2):373–378

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hoffstedt J, Eriksson P, Mottagui-Tabar S et al (2002) A polymorphism in the leptin promoter region (–2548 G/A) influences gene expression and adipose tissue secretion of leptin. Horm Metab Res 34:355–359

    Article  CAS  PubMed  Google Scholar 

  • Hossein H, Mahroo M, Abbas A, Firouzeh A, Nadia H (2004) Cytokine production by peripheral blood mononuclear cells in recurrent miscarriage. Cytokine 28(2):83–6

    Article  CAS  PubMed  Google Scholar 

  • Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR (2006) The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126:1121–1133

    Article  CAS  PubMed  Google Scholar 

  • Kawaguchi M, Takahashi D, Hizawa N, Suzuki S, Matsukura S, Kokubu F et al (2006) IL-17 F sequence variant (His161Arg) is associated with protection against asthma and antagonizes wild-type IL-17 F activity. J Allergy Clin Immunol 117(4):795–801

    Article  CAS  PubMed  Google Scholar 

  • Kim KH, Kim YJ, Lee S, Oh SW, Lee K, Park Y et al (2008) Evaluation of plasma leptin levels & BMI as predictor of postpartum weight retention. Indian J Med Res 128(5):595–600

    PubMed  Google Scholar 

  • Kroon B, Harrison K, Martin N, Wong B, Yazdani A (2011) Miscarriage karyotype and its relationship with maternal body mass index, age, and mode of conception. Fertil Steril 95(5):1827–1829

    Article  PubMed  Google Scholar 

  • Laird SM, Quinton ND, Anstie B, Li TC, Blakemore AI (2001) Leptin and leptin-binding activity in women with recurrent miscarriage: correlation with pregnancy outcome. Hum Reprod 16(9):2008–2013

    Article  CAS  PubMed  Google Scholar 

  • Landres IV, Milki AA, Lathi RB (2010) Karyotype of miscarriages in relation to maternal weight. Hum Reprod 25(5):1123–1126

    Article  PubMed  Google Scholar 

  • Le Stunff C, Le Bihan C, Schork NJ, Bougneres P (2000) A common promoter variant of the leptin gene is associated with changes in the relationship between serum leptin and fat mass in obese girls. Diabetes 49:2106–2200

    Article  Google Scholar 

  • Lee SK, Kim JY, Hur SE, Kim CJ, Na BJ, Lee M, Gilman-Sachs A, Kwak-Kim J (2011) An imbalance in interleukin-17- producing T and Foxp31 regulatory T cells in women with idiopathic recurrent pregnancy loss. Hum Reprod 26(11):2964–2971

    Article  CAS  PubMed  Google Scholar 

  • Liu L, Yang P, He H, Lin X, Jiang L, Chi W et al (2008) Leptin increases in Vogt-Koyanagi-Harada (VKH) disease and promotes cell proliferation and inflammatory cytokine secretion. Br J Ophthalmol 92:557–561

    Article  CAS  PubMed  Google Scholar 

  • Moschos S, Chan JL, Mantzoros CS (2002) Leptin and reproduction: a review. Fertil Steril 77(3):433–444

    Article  PubMed  Google Scholar 

  • Najafi S, Hadinedoushan H, Eslami G, Aflatoonian A (2014) Association of IL-17A and IL-17 F gene polymorphisms with recurrent pregnancy loss in Iranian women. J Assist Reprod Genet 31(11):1491–6

    Article  PubMed Central  PubMed  Google Scholar 

  • Nakashima A, Ito M, Shima T, Bac ND, Hidaka T, Saito S (2010) Accumulation of IL-17-positive cells in decidua of inevitable abortion cases. Am J Reprod Immunol 64(1):4–11

    PubMed  Google Scholar 

  • Orlova EG, Shirshev SV (2014) Role of leptin and ghrelin in induction of differentiation of IL-17-producing and T-regulatory cells. Exp Biol Med 156(6):819–822

    Article  CAS  Google Scholar 

  • Pappu BP, Angkasekwinai P, Dong C (2008) Regulatory mechanisms of helper T cell differentiation: new lessons learned from interleukin 17 family cytokines. Pharmacol Ther 117:374–384

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Paz-Filho GJ, Volaco A, Suplicy HL, Radominski RB, Boguszewski CL (2009) Decrease in leptin production by the adipose tissue in obesity associated with severe metabolic syndrome. Arq Bras Endocrinol Metabol 53(9):1088–95

    Article  PubMed  Google Scholar 

  • Pei L, Yang F, Zhang C, Guo M, Bao J, Lu H, Huo Z (2013) A variant in interleukin-2 gene is associated with repeated spontaneous abortion in Ningxia Han people. Open J Obstet Gynaecol 3:32–36

    Article  CAS  Google Scholar 

  • Saifi B, Rezaee SA, Tajik N, Ahmadpour ME, Ashrafi M, Vakili R, SoleimaniAsl S, Aflatoonian R, Mehdizadeh M (2014) Th17 cells and related cytokines in unexplained recurrent spontaneous miscarriage at the implantation window. Reprod Biomed Online 29(4):481–9

    Article  CAS  PubMed  Google Scholar 

  • Stephenson MD (1996) Frequency of factors associated with habitual abortion in 197 couples. Fertil Steril 66(1):24–9

    CAS  PubMed  Google Scholar 

  • Sumarac-Dumanovic M, Stevanovic D, Ljubic A, Jorga J, Simic M, Stamenkovic-Pejkovic D, Starcevic V, Trajkovic V, Micic D (2009) Increased activity of interleukin-23/interleukin-17 proinflammatory axis in obese women. Int J Obes 33:151–156

    Article  CAS  Google Scholar 

  • Tommaselli GA, Di Spiezio SA, Di Carlo C, Bifulco G, Cerrota G, Cirillo D et al (2006) Do serum leptin levels have a role in the prediction of pregnancy outcome in case of threatened miscarriage? Clin Endocrinol (Oxf) 65(6):772–775

    Article  CAS  Google Scholar 

  • Verma PK, Prakash S, Parveen F, Faridi RM, Agrawal S (2012) Genetic association of adipokine and UCP2 polymorphism with recurrent miscarriage among non-obese women. Reprod Biomed Online 25(5):527–35

    Article  CAS  PubMed  Google Scholar 

  • Wang WJ, Hao CF, Yi L, Yin GJ, Bao SH, Qiu LH et al (2010a) Increased prevalence of T helper 17 (Th17) cells in peripheral blood and decidua in unexplained recurrent spontaneous abortion patients. J Reprod Immunol 84:164–170

    Article  CAS  PubMed  Google Scholar 

  • Wang WJ, Hao CF, Qu QL, Wang X, Qiu LH, Lin QD (2010b) The deregulation of regulatory T cells on interleukin-17-producing T helper cells in patients with unexplained early recurrent miscarriage. Hum Reprod 25:2591–2596

    Article  CAS  PubMed  Google Scholar 

  • World Health Organisation (1995) Physical status: the use and interpretation anthropometry: report of a WHO Expert Committee, WHO Technical Report Series. WHO, Geneva 854:321–344

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Haidy E. Zidan.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zidan, H.E., Rezk, N.A., Alnemr, A.A.A. et al. Interleukin-17 and leptin genes polymorphisms and their levels in relation to recurrent pregnancy loss in Egyptian females. Immunogenetics 67, 665–673 (2015). https://doi.org/10.1007/s00251-015-0876-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00251-015-0876-8

Keywords

Navigation