Genetic Association between Inflammatory-Related Polymorphism in STAT3, IL-1β, IL-6, TNF-α and Idiopathic Recurrent Implantation Failure

Min Jung Kwon; Ji Hyang Kim; Kyu Jae Kim; Eun Ju Ko; Jeong Yong Lee; Chang Su Ryu; Yong Hyun Ha; Young Ran Kim; Nam Keun Kim

doi:10.3390/genes14081588

Genetic Association between Inflammatory-Related Polymorphism in STAT3, IL-1β, IL-6, TNF-α and Idiopathic Recurrent Implantation Failure

Genes (Basel). 2023 Aug 5;14(8):1588. doi: 10.3390/genes14081588.

Authors

Min Jung Kwon¹, Ji Hyang Kim², Kyu Jae Kim¹, Eun Ju Ko¹, Jeong Yong Lee¹, Chang Su Ryu¹, Yong Hyun Ha¹, Young Ran Kim², Nam Keun Kim¹

Affiliations

¹ Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13496, Republic of Korea.
² Department of Obstetrics and Gynecology, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam 13496, Republic of Korea.

Abstract

Recurrent implantation failure (RIF) is defined as a failure to achieve pregnancy after multiple embryo transfers. Implantation is closely related to inflammatory gradients, and interleukin-1beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) play a key role in maternal and trophoblast inflammation during implantation. Signal transducer and activator of transcription 3 (STAT3) interacts with cytokines and plays a critical role in implantation through involvement in the inflammation of the embryo and placenta. Therefore, we investigated 151 RIF patients and 321 healthy controls in Korea and analyzed the association between the polymorphisms (STAT3 rs1053004, IL-1β rs16944, IL-6 rs1800796, and TNF-α rs1800629, 1800630) and RIF prevalence. In this paper, we identified that STAT3 rs1053004 (AG, adjusted odds rate [AOR] = 0.623; p = 0.027; GG, AOR = 0.513; p = 0.043; Dominant, AOR = 0.601, p = 0.011), IL-6 rs1800796 (GG, AOR = 2.472; p = 0.032; Recessive, AOR = 2.374, p = 0.037), and TNF-α rs1800629 (GA, AOR = 2.127, p = 0.010, Dominant, AOR = 2.198, p = 0.007) have a significant association with RIF prevalence. This study is the first to investigate the association of each polymorphism with RIF prevalence in Korea and to compare their effect based on their function on inflammation.

Keywords: IL-1β; IL-6; Recurrent implantation failure (RIF); STAT3; TNF-α; interleukin (IL); single nucleotide polymorphism (SNP).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Female
Humans
Inflammation
Interleukin-1beta / genetics
Interleukin-6 / genetics
Pregnancy
STAT3 Transcription Factor* / genetics
Tumor Necrosis Factor-alpha* / genetics

Substances

Tumor Necrosis Factor-alpha
Interleukin-1beta
STAT3 Transcription Factor
Interleukin-6
STAT3 protein, human

Grants and funding

This research was supported by National Research Foundation of Korea (NRF) grants funded by the Korean Government (MSIT; grant numbers 2022R1F1A1064169 and 2022R1F1A1074986). This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant number: HR22C1605).