Interleukin 6 (IL-6) and Tumor Necrosis Factor α (TNF-α) Single Nucleotide Polymorphisms (SNPs), Inflammation and Metabolism in Gestational Diabetes Mellitus in Inner Mongolia

Abstract

BACKGROUND Gestational diabetes mellitus (GDM) is common all over the world. GDM women are with inflammatory and metabolisms abnormalities. However, few studies have focused on the association of IL-65-72C/G and TNF-α -857C/T single nucleotide polymorphisms (SNPs), inflammatory biomarkers, and metabolic indexes in women with GDM, especially in the Inner Mongolia population. The aim of this study was to investigate the associations of IL-65-72C/G and TNF-α -857C/T SNPs, and inflammation and metabolic biomarkers in women with GDM pregnancies. MATERIAL AND METHODS Blood samples and placentas from 140 women with GDM and 140 women with healthy pregnancies were collected. Matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) and MassARRAY-IPLEX were performed to analyze IL-65-72C/G and TNF-α -857C/T SNPs. Enzyme linked immunosorbent assay (ELISA) was performed to analyze inflammatory biomarkers and adipokines. RESULTS Distribution frequency of TNF-α -857CT (OR=3.316, 95% CI=1.092-8.304, p=0.025) in women with GDM pregnancies were obviously higher than that in women with healthy pregnancies. Women with GDM were of older maternal age, had higher BMI, were more nulliparous, and had T2DM and GDM history, compared to women with healthy pregnancies (p<0.05). Inflammatory biomarkers in serum (hs-CRP, IL-6, IL-8, IL-6/IL-10 ratio) and placental (NF-κB, IL-6, IL-8, IL-6/IL-10 ratio, IL-1b, TNF-α) were significantly different (p<0.05) between women with GDM and women with healthy pregnancies. Differences were found for serum FBG, FINS, HOMA-IR, and HOMA-β, and placental IRS-1, IRS-2, leptin, adiponectin, visfatin, RBP-4, chemerin, nesfatin-1, FATP-4, EL, LPL, FABP-1, FABP-3, FABP-4, and FABP-5. CONCLUSIONS TNF-α -857C/T SNP, hs-CRP, IL-6, IL-8, and IL-6/IL-10 were associated with GDM in women from Inner Mongolia, as was serious inflammation and disordered lipid and glucose metabolisms.

Figure 1

Comparisons of distribution frequencies of genotypes and alleles on IL-65–72C/G and TNF-r -857C/T in pregnancies with or without GDM. (A) Mass spectrometry for IL-65–72C/G; (B) distribution frequencies for IL-65–72C/G; (C) mass spectrometry for TNF-α-857C/T; (D) distribution frequencies for TNF-e -857C/T). GDM – gestational diabetes mellitus; IL-6 – interleukin-6; TNF-α – tumor necrosis factor-α.

Figure 2

Comparisons on serum and/or placental inflammatory biomarkers and/or adipokines of pregnancies with or without GDM. (A) Serum inflammatory factors; (B) placental inflammatory factors and adipokines, * p<0.05). GDM – gestational diabetes mellitus; hs-CRP – high sensitivity C-reactive protein; IL – interleukin; TNF-α – tumor necrosis factor-α; NF-κB – nuclear factor-κB; RBP – retinol-binding protein; irs-1 – insulin receptor substrate-1; FATP – fatty acid transport protein; EL – endothelial lipase; LPL – low density lipoprotein; FABP – fatty acid binding protein.