Gestational diabetes mellitus (GDM), defined as carbohydrate intolerance diagnosed for the first time during pregnancy, affects both maternal and fetal health. Possession of a specific genetic polymorphism can be a predisposing factor for susceptibility to some diseases. The aim of this study was to investigate the association between single nucleotide polymorphisms (SNP) in the promoter gene of interleukin-10 (IL-10) as well as tumor necrosis factor-alpha (TNF alpha) with the development of GDM. Two hundred and twelve consecutive series of eligible normal pregnant women (controls) and gestational diabetes mellitus women were selected based on the study's inclusion and exclusion criteria. DNA was extracted from blood and genotyped for IL-10 at three positions and TNF alpha for gene polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Plasma levels of IL-10 and TNF alpha at different gestational periods as well as postpartum were quantified using enzyme linked immunosorbent assay (ELISA). The results of the study showed that the difference in the frequency of SNP at position -597 in the promoter of the human IL-10 gene between the control and GDM groups was statistically significant (p < 0.05). In contrast, there was no significant difference in the frequency of SNP at the other two sites in the promoter region of the human IL-10 gene (-824 and -1082) as well as position -308 in the promoter of the human TNF-alpha (p > 0.05). In addition, there was no significant difference between the two groups in terms of plasma levels of IL-10 as well as TNF alpha in different stages of pregnancy. SNP at position -597 was significantly associated with the development of GDM and shows potential for use as a predictive marker for GDM.
OBJECTIVE: The aim of this study is to investigate if an association exists between single nucleotide polymorphism (SNP) in the tumor necrosis factor-alpha (TNF-alpha) and TNF-beta genes.
METHODS: The DNA was extracted and SNP in the human TNF-alpha and TNF-beta genes at positions -308 (G/A) and 252 (A/G), respectively, was analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Plasma levels of TNF-alpha in different stages of pregnancy were quantified using enzyme linked immunosorbent assay (ELISA).
RESULTS: There was no significant difference in genotype and allele frequency of SNP at position -308 (G/A) in the promoter region of the human TNF-alpha gene as well as the SNP at position 252 (A/G) in the human TNF-beta gene between the GDM and control subjects. Using the logistic regression model, it was found that the SNP in the TNF-alpha as well as TNF-beta were not associated with development of GDM. In addition, the TNF-alpha levels in the plasma of GDM and control mothers were not significantly different.
CONCLUSIONS: In the population studied, the SNP in position -308 (G/A) of the human TNF-alpha or in position 252 (A/G) of the human TNF-beta gene is not an independent risk factor or a predictor for GDM.