Author(s):
Weaam Gouda, Lamiaa Mageed, Ahmed Okasha, Shaimaa Ellithy, Mie Afify
Email(s):
weaamgoudaali@gmail.com , lamiaamageed@gmail.com , drfifthyear@yahoo.com , Shy.obgyn@yahoo.com , mieafify@yahoo.com
DOI:
10.52711/0974-360X.2026.00399 
Address:
Weaam Gouda1, Lamiaa Mageed1*, Ahmed Okasha2, Shaimaa Ellithy3, Mie Afify1
1Biochemistry Department, Biotechnology Research Institute, National Research Centre, Giza, Egypt.
2Reproductive Health and Family Planning Department, National Research Centre, Giza, Egypt.
3Obstetrics and Gynecology Department, El Galaa Teaching Hospital, Cairo, Egypt.
*Corresponding Author
Published In:
Volume - 19,
Issue - 6,
Year - 2026
ABSTRACT:
The identification of a possible biomarker for preeclampsia, a complex hypertension condition specific to pregnancy that affects maternal and fetal health globally and has a prevalence of 2–8%, opens the door for its prediction in the early stages of pregnancy. According to studies, irisin, a byproduct of fibronectin type III domain containing protein 5 (FNDC5), is linked to pregnancies that are complicated by preeclampsia as opposed to third-trimester pregnancies that are healthy and normal. The current study was aimed to ascertain the genotypic and allelic frequencies of the four single nucleotide polymorphisms (SNPs) in the FNDC5/irisin gene (rs1298190, rs726344, rs1746661, and rs3480) in preeclamptic as well as normal pregnant women. Additionally, to elucidate the genetic association between these SNPs and preeclampsia susceptibility. Furthermore, we evaluate the above-mentioned SNPs' potential value as useful biomarkers for determining the likelihood of having PE. This study was a case–control study conducted at Department of Obstetrics and Gynecology, El Galaa Teaching Hospital ching Hospital. Totally 120 pregnant women were enrolled in the study; 60 of them were preeclamptic patients and the other 60 were healthy pregnant women assigned as a control group. The four SNPs (rs1298190, rs726344, rs1746661, rs3480) in the FNDC5/irisin gene were assessed to all participants by real-time polymerase chain reaction (RT-PCR) technique. There was a significant statistical difference between the two studied groups regarding genotype frequency of FNDC5 (Irisin) rs3480, rs726344, rs174661, and rs1298190. Regarding rs3480 (A/G), there was a high frequency of GG genotype and G allele frequency among preeclamptic group. Concerning rs726344 (G/A), the frequency of the genotypes (AA and GA) as well as A allele were the highest in the preeclamptic patients. Regarding rs1746661 (G/T), the frequency of TT genotype and T allele had the highest frequency among PE group. For rs1298190, the preeclampsia group had high risk of GG and AG genotypes and G allele as compared to normotensive pregnant women. Moreover, the ROC analysis for the combination of the studied gene polymorphisms revealed high accuracy (92.5%) with P value < 0.001. The outcome of work revealed that the irisin (FNDC5) gene may be a potential biomarker for preeclampsia-complicated pregnancies. Nevertheless, more studies are required using distinct cohorts and additional FNDC5 gene variations or other irisin signaling-related genes.
Cite this article:
Weaam Gouda, Lamiaa Mageed, Ahmed Okasha, Shaimaa Ellithy, Mie Afify. Investigation of Irisin (FNDC5) Gene Polymorphisms in Normotensive and Preeclamptic Pregnancies. Research Journal Pharmacy and Technology. 2026;19(6):2794-0. doi: 10.52711/0974-360X.2026.00399
Cite(Electronic):
Weaam Gouda, Lamiaa Mageed, Ahmed Okasha, Shaimaa Ellithy, Mie Afify. Investigation of Irisin (FNDC5) Gene Polymorphisms in Normotensive and Preeclamptic Pregnancies. Research Journal Pharmacy and Technology. 2026;19(6):2794-0. doi: 10.52711/0974-360X.2026.00399 Available on: https://rjptonline.org/AbstractView.aspx?PID=2026-19-6-56
REFERENCES:
1. Nasir I, Rahim A, Afzal M, Ayub S, Bashir Z, Zakria N. SLC19A1 Gene Polymorphism; Risk Factor for Preeclampsia. J Coll Physicians Surg Pak. 2025; 35(3): 306-312. doi: 10.29271/jcpsp.2025.03.306. PMID: 40055164.
2. 2.Nirupama R, Divyashree S, Janhavi P, Muthukumar SP, Ravindra PV. Preeclampsia: Pathophysiology and Management. J Gynecol Obstet Hum Reprod. 2021; 50(2): 101975. doi: 10.1016/j.jogoh.2020.101975. Epub 2020 Nov 7. PMID: 33171282.
3. Malhan A, Hyder M, Baloch S, Zahegul, Roshan S, Dembra G, Arshad, M. (2023). Frequency of preeclampsia in pregnant women presenting in a tertiary hospital. Pak J Health Sci 2023; 4(4): 30-3. doi: 10.54393/pjhs. v4i04.652.
4. Olaniyan MF, Akpoyovwere OJ, Kanikwu NP, Olaniyan TB, Adeniran MA, Muhibi MA, Odegbemi OB. Genetic polymorphisms associated with preeclampsia risk in Nigerian women. Egypt J Med Hum Genet. 2024; 25: 109. doi: 10.1186/ s43042-024-00585-4
5. Smitha Jose, Manjima M J, Nidhi Alex, Santy M Thampi. A Study to Assess the effect of Jigsaw Learning Technique to Learn the Concept of Preeclampsia among Fourth year B.Sc. Nursing students of TMM College of Nursing, Tiruvalla. Asian Journal of Nursing Education and Research. 2023; 13(3): 184-8. doi: 10.52711/2349-2996.2023.00039
6. Nissa FU, Mehboob W, Naqvi R, Jabbar S, Zaidi SA, Fatima ST. Pregnancy-induced hypertension among pregnant women delivering in a tertiary care center. Pak J Med Health Sci. 2022; 16(5). doi: 10.53350/pjmhs22165709.
7. Shivaleela S Sarawad. Maternal Health and Preeclampsia Prevention: A Community-Based Approach. Asian Journal of Nursing Education and Research. 2025; 15(2): 109-0. doi: 10.52711/2349-2996.2025.00024
8. Gupta K, Chakrabarti S, Singh SP, Choudhary S. Role of gene polymorphisms and their influence on preeclampsia: a systematic review. J Obstet Gynaecol Res. 2022; 48(7): 2109–2125
9. Saito S, Nakashima A. A review of the mechanism for poor placentation in early-onset preeclampsia: the role of autophagy in trophoblast invasion and vascular remodeling. J Reprod Immunol. 2014 Mar;101-102: 80-88. doi: 10.1016/j.jri.2013.06.002. Epub 2013 Aug 2. PMID: 23969229.
10. Smitha Jose, Manjima M J, Nidhi Alex, Santy M Thampi. A Study to Assess the effect of Jigsaw Learning Technique to Learn the Concept of Preeclampsia among Fourth year B.Sc. Nursing students of TMM College of Nursing, Tiruvalla. Asian Journal of Nursing Education and Research. 2023; 13(3): 184-8. doi: 10.5958/0974-360X.2016.00329.2
11. Kasrineh FA, Esmaeili OS, Tavakoli T, Khalili P, Rajabi Z, Vatankhah H, Hajizadeh MR, Mahmoodi M, Hakimi H, Jalali Z. Prenatal irisin is inversely related to the term placental telomere length. BMC Res Notes. 2025; 18(1): 102. doi: 10.1186/s13104-025-07118-1. PMID: 40057798; PMCID: PMC11890717.
12. Caska H, Akbas H, Sak S. Investıgatıon of Irısın (Fndc5) Gene Polymorphısms In Patıents Wıth Gestatıonal Dıabetes Mellıtus. Int J Endocrinol Diabetes. 2023; 6(1): 144 https://doi.org/ 10.36266/IJED/144
13. Drewlo S, Johnson E, Kilburn BA, Kadam L, Armistead B, Kohan-Ghadr HR. Irisin induces trophoblast differentiation via AMPK activation in the human placenta. J Cell Physiol. 2020; 235(10): 7146-7158. doi: 10.1002/jcp.29613. Epub 2020 Feb 5. PMID: 32020629.
14. Lu M, Sferruzzi-Perri AN. Placental mitochondrial function in response to gestational exposures. Placenta. 2021; 104: 124-137. doi: 10.1016/j.placenta.2020.11.012. Epub 2020 Dec 5. PMID: 33338764.
15. Farhan FS, Findakly SB, Sersam LW. Serum irisin levels in normotensive and preeclamptic pregnancies. Mustansiriya Med J. 2018; 17: 80-4. doi:10.4103/MJ. MJ_22.18
16. Khidr EG, Ali SS, Elshafey MM, Fawzy OA. Association of irisin and FNDC5 rs16835198 G>T gene polymorphism with type 2 diabetes mellitus and diabetic nephropathy. An Egyptian pilot study. Gene. 2017 Aug 30; 626: 26-31. doi: 10.1016/ j.gene.2017.05.010. Epub 2017 May 4. PMID: 28479383.
17. Zbucka-Kretowska M, Kuzmicki M, Telejko B, Goscik J, Ciborowski M, Lipinska D, Hryniewicka J, Citko A, Lawicki S, Wolczynski S. First-trimester irisin and fetuin-A concentration in predicting macrosomia. J Matern Fetal Neonatal Med. 2019; 32(17): 2868-2873. doi: 10.1080/14767058.2018.1450859. Epub 2018 Mar 21. PMID: 29562796.
18. Irianti E, Ilyas S, Salomo Hutahaen, Rosidah. The Role of EVOO (Extra Virgin Olive Oil) in Serum MDA Concentration and Blood Pressure of Pregnant Mice (Rattus norvegicus) with Pre-eclampsia. Research J. Pharm. and Tech. 2018; 11(3): 1053-1057. doi: 10.5958/0974-360X.2018.00197.X
19. Sergey Kotelevets, Sergey Chekh, Zukhra Karakotova. Modern Possibilities of the Use of Non-Invasive Serological Biomarkers Severe in Population Studies. Research J. Pharm. and Tech. 2019; 12(9): 4274-4282. doi: 10.5958/0974-360X.2019.00735.2
20. Tianxin Sheng, Yunhe Lu, Kangjuan Yang, Yan Jin, Yinghua Wu, Zibo Zhang, YanhuaJin, XiongjiJin. Association Between Single Nucleotide Polymorphisms (SNPs) in the Promoter of Adiponectin Gene, Hypoadiponectinemia, and Diabetes. Research J. Science and Tech. 2016; 8(1): 34-40. doi: 10.5958/2349-2988.2016.00004.8
21. Program NHBPE: Report of the national high blood pressure education program working group on high blood pressure in pregnancy. American journal of obstetrics and gynecology 2000; 183(1): s1-s22.
22. Abdu Allah AM, Abd El Gayed EM, Hammoudah S, El-Attar L, Lama, Shehabeldin W. (2017). Irisin Gene Polymorphism Rs3480 and Rs1746661and Obesity in Egyptian Populations. IOSR Journal of Biotechnology and Biochemistry. 2017; 03: 48-54. doi:10.9790/264X-03034854.
23. Brondani LA, Boelter G, Assmann TS, Leitão CB, Canani LH, Crispim D. Irisin-encoding gene (FNDC5) variant is associated with changes in blood pressure and lipid profile in type 2 diabetic women but not in men. Metabolism. 2015; 64(9): 952-7. doi: 10.1016/j.metabol.2015.05.005. Epub 2015 May 14. PMID: 26024756.
24. Salem H, Yatchenko Y, Anosov M, Rosenfeld T, Altarescu G, Grisaru-Granovsky S, Birk R. Maternal and neonatal irisin precursor gene FNDC5 polymorphism is associated with preterm birth. Gene. 2018 Apr 5; 649: 58-62. doi: 10.1016/j.gene.2018.01.097. Epub 2018 Jan 31. PMID: 29408625.
25. Kasrineh FA, Esmaeili OS, Tavakoli T, Khalili P, Rajabi Z, Vatankhah H, Hajizadeh MR, Mahmoodi M, Hakimi H, Jalali Z. Prenatal irisin is inversely related to the term placental telomere length. BMC Res Notes. 2025; 18(1): 102. doi: 10.1186/s13104-025-07118-1. PMID: 40057798; PMCID: PMC11890717.
26. Wasan K. Jawad, Ali M. Kadhim, Ahmed M. Issa, Rahman S. Zabibah. New Preeclampsia Calculated Factor (PF) Detecting Severity in Healthy, Mild and Severe Cases. Research Journal of Pharmacy and Technology. 2024; 17(9): 4154-0. doi: 10.52711/ 0974-360X.2024.00643
27. Savio Simon, Viji Krishnan, Lola Ramachandran. A Hospital-based Study on assessing the significance of Serum Lactate dehydrogenase level in Preeclampsia and its association with Maternal and Fetal outcome. Research Journal of Pharmacy and Technology. 2024; 17(5): 2109-3. doi: 10.52711/0974-360X.2024.00334
28. Al-Daghri NM, Mohammed AK, Al-Attas OS, Amer OE, Clerici M, Alenad A, Alokail MS. SNPs in FNDC5 (irisin) are associated with obesity and modulation of glucose and lipid metabolism in Saudi subjects. Lipids Health Dis. 2016 Mar 11; 15:54. doi: 10.1186/s12944-016-0224-5. PMID: 26968837; PMCID: PMC4788945.
29. Tang S, Zhang R, Jiang F, Wang J, Chen M, Peng D, Yan J, Bao Y, Hu C, Jia W. An interaction between a FNDC5 variant and obesity modulates glucose metabolism in a Chinese Han population. PLoS One. 2014; 9(11): e109957. doi: 10.1371/ journal.pone.0109957. PMID: 25369206; PMCID: PMC4219676.
30. Tanisawa K, Taniguchi H, Sun X, Ito T, Cao ZB, Sakamoto S, Higuchi M. Common single nucleotide polymorphisms in the FNDC5 gene are associated with glucose metabolism but do not affect serum irisin levels in Japanese men with low fitness levels. Metabolism. 2014; 63(4): 574-83. doi: 10.1016/ j.metabol.2014.01.005. Epub 2014 Jan 17. PMID: 24559842.
31. Staiger H, Böhm A, Scheler M, Berti L, Machann J, Schick F, Machicao F, Fritsche A, Stefan N, Weigert C, Krook A, Häring HU, de Angelis MH. Common genetic variation in the human FNDC5 locus, encoding the novel muscle-derived 'browning' factor irisin, determines insulin sensitivity. PLoS One. 2013; 8(4): e61903. doi: 10.1371/journal.pone.0061903. PMID: 23637927; PMCID: PMC3636229.
32. Sanchis-Gomar F, Garatachea N, He ZH, Pareja-Galeano H, Fuku N, Tian Y, Arai Y, Abe Y, Murakami H, Miyachi M, Yvert T, Santiago C, Venturini L, Fiuza-Luces C, Santos-Lozano A, Rodríguez-Romo G, Ricevuti G, Hirose N, Emanuele E, Lucia A. FNDC5 (irisin) gene and exceptional longevity: a functional replication study with rs16835198 and rs726344 SNPs. Age (Dordr). 2014; 36(6): 9733. doi: 10.1007/s11357-014-9733-1. Epub 2014 Nov 27. PMID: 25427998; PMCID: PMC4245403.
33. Park KH, Zaichenko L, Brinkoetter M, Thakkar B, Sahin-Efe A, Joung KE, Tsoukas MA, Geladari EV, Huh JY, Dincer F, Davis CR, Crowell JA, Mantzoros CS. Circulating irisin in relation to insulin resistance and the metabolic syndrome. J Clin Endocrinol Metab. 2013; 98(12): 4899-907. doi: 10.1210/jc.2013-2373. Epub 2013 Sep 20. Erratum in: J Clin Endocrinol Metab. 2014 May;99(5):1910. PMID: 24057291; PMCID: PMC3849667.
34. Mayrink J, Souza RT, Feitosa FE, Rocha Filho EA, Leite DF, Vettorazzi J, Calderon IM, Sousa MH, Costa ML, Baker PN, Cecatti JG; Preterm SAMBA study group. Incidence and risk factors for Preeclampsia in a cohort of healthy nulliparous pregnant women: a nested case-control study. Sci Rep. 2019; 9(1): 9517. doi: 10.1038/s41598-019-46011-3. PMID: 31266984; PMCID: PMC6606578.
35. Mora-Palazuelos C, Bermúdez M, Aguilar-Medina M, Ramos-Payan R, Ayala-Ham A, Romero-Quintana JG. Cytokine-polymorphisms associated with Preeclampsia: A review. Medicine (Baltimore). 2022; 101(39): e30870. doi: 10.1097/ MD.0000000000030870. PMID: 36181055; PMCID: PMC9524891.
36. Digvijay Kadam, Yamini Patil, R. P. Patange, Supriya Patil, Shiju Sebastian, Ravindra Jarag. Relationships between Ultrasonographic Placental Thickness in the Third Trimester and Foetal Outcomes. Research Journal of Pharmacy and Technology. 2024; 17(2): 746-0. doi: 10.52711/0974-360X.2024.00116
37. Simerjeet Kaur Chahal, Atul Kabra, Rupinder Kaur Sodhi. Novel biomarkers in Polycystic Ovary Syndrome. Research Journal of Pharmacy and Technology. 2024; 17(1): 439-2. doi: 10.52711/ 0974-360X.2024.00069
38. Shaimaa Ellithy, Weaam Gouda, Lamiaa Mageed, Ahmed Okasha, Mie Afify. Gene Polymorphisms of TCF7L2 and Risk of Preeclampsia in Pregnant Women. Clin. Lab. 2026; 72. doi: 10.7754/Clin.Lab.2025.250443