Polymorphisms in proinflammatory cytokine genes, effect on gene expression and association with preterm delivery in Saudi females
2018
Genetic polymorphism in proinflammatory cytokine genes may be associated with the etiology of preterm birth (PTB). The current study was designed with the aim to explore the association of genetic polymorphisms and mRNA expression of IL-1α, IL-1β, and TNF-α gene with preterm birth in the Saudi population. Genotyping of genomic DNA of 50 PTB patients and an equal number of controls were carried out using TaqMan Genotyping assay kits. Gene expression of each gene was carried out using quantitative RT-PCR. The cytokine levels in the serum of PTB patients and controls were measured by ELISA. A statistically significant association was observed between the rs361525 alleles (G and A) of TNF-α and PTB, where the mutant A allele was significantly protective against PTB development (OR= 0.362; χ2=4.31; p=0.038). The gene expression of all studied genes (IL1α, IL-1β, IL-6, and TNF-α) was higher in the PTB patients, but the results reached significance only for IL-1β (p=0.035). Elevated gene expression was also evident from the level of these proteins in plasma, where the level of IL1α, IL-β were significantly higher in the serum of PTB patients compared to the controls, however, IL6 and TNF-α were significantly lower despite higher gene expression. For IL6, the lower level could be due to tocolytic treatment that was given to all women suffering from PTB. Receiver operating curves (ROC) were drawn for the studied cytokines. In conclusion, this study revealed that rs361525 polymorphism plays a role as a protective marker for PTB and the levels of IL-1α, IL-6, TNF- α can be used as predicative biomarkers for PTB I Saudi women.
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