Role of IL-6, IL-10 and TNFα Gene Variants in Preterm Birth

Mirta Kadivnik; Deni Plečko; Kristina Kralik; Nena Arvaj; Jasenka Wagner

doi:10.3390/jcm13082429

Role of IL-6, IL-10 and TNFα Gene Variants in Preterm Birth

J Clin Med. 2024 Apr 21;13(8):2429. doi: 10.3390/jcm13082429.

Authors

Mirta Kadivnik^{1

2}, Deni Plečko³, Kristina Kralik⁴, Nena Arvaj³, Jasenka Wagner³

Affiliations

¹ Clinic of Obstetrics and Gynecology, University Hospital Center Osijek, J. Huttlera 4, 31000 Osijek, Croatia.
² Department of Obstetrics and Gynecology, Faculty of Medicine, J.J. Strossmayer University, J. Huttlera 4, 31000 Osijek, Croatia.
³ Department of Medical Biology and Genetics, Faculty of Medicine, J.J. Strossmayer University, J. Huttlera 4, 31000 Osijek, Croatia.
⁴ Department of Medical Statistics and Informatics, Faculty of Medicine, J.J. Strossmayer University, J. Huttlera 4, 31000 Osijek, Croatia.

Abstract

Background: The association of gene variants for interleukin 6 (IL-6) (rs1800796), interleukin 10 (IL-10) (rs1800896) and tumor necrosis factorα (TNFα (rs1800629) with the occurrence of spontaneous preterm birth (PTB) was investigated to determine whether these genetic variants are a risk factor. Methods: A total of 199 blood samples from pregnant women who had given birth prematurely and 200 control blood samples were analyzed to determine single nucleotide polymorphisms (SNPs) of genes for IL-6 (rs1800796), IL-10 (rs1800896) and TNFα (rs1800629). The control samples were samples from pregnant women with term delivery. The isolation of DNA was performed on mini-spin columns according to the manufacturer's protocol. The quality and purity of the isolated DNA were tested using a Qubit 3 fluorometer. Genotyping was performed with an ABI PRISM 7500 SDS using TaqMan SNP genotyping assays. The genotypes obtained were analyzed using the 7500 Software v2.3 package. Results: Carriers of the A/A genotype for the rs1800629 SNP of the TNFα gene have a 4.81 times greater chance of late-onset PTB compared to carriers of the G/G and A/G genotypes in the recessive inheritance model. The presence of the G/G genotype in the recessive inheritance model compared with the G/A and A/A genotypes for the rs1800896 SNP of the IL-10 gene represents a potentially protective factor, with mothers in the term-birth group having an almost 2-fold lower odds of PTB in general and an almost 10-fold lower odds of early PTB. On the other hand, carriers of the A/G genotype of rs1800896 have a 1.54-fold higher chance of preterm birth in general and a 1.6-fold higher chance of late preterm birth in the superdominant inheritance model compared to the A/A and G/G genotypes in the group of mothers with PTB. In this study, no association was found between PTB and the rs1800796 SNP of the IL-6 gene. Conclusions: rs1800629 in mothers was associated with PTB. rs1800896 shows a potentially protective effect for the occurrence of PTB in this study. No association was found between PTB and rs1800796.

Keywords: cytokines; inflammation; interleukins; premature birth; single nucleotide polymorphisms.

Grants and funding

VIF2017-MEFOS-3/Medical faculty Osijek