Inflammatory cytokine gene polymorphisms and spontaneous preterm birth.
ABSTRACT The objective was to search for an association between spontaneous preterm birth (sPTB) and single and/or combined polymorphisms in genes TNFA -308 G>A, IL10 -1082 G>A, IL10 -819 C>T, IL10 -592 C>A, IL6 -174 G>C, and IFNG +874 A>T. Genotyping was performed on 410 Brazilian ethnically matched women managed at two hospitals (two independent case-control sets). One set consisted of 122 cases and 101 controls, and the other set comprised 82 cases and 105 controls. We compared genotype and genotype-combination frequencies between cases and controls using Fisher's exact or the chi(2) tests and confirmed results using logistic regression. Among the six SNPs studied, we found no independent association between any single SNP and sPTB risk. The multi-locus analysis revealed a significant association between sPTB and the TNFA(GG)/IL6(GG)/IFNG(AA) genotype combination (p=0.002), confirmed by logistic regression. Our data suggest that the combination of TNF-alpha, IFN-gamma, and IL-6 maternal gene polymorphisms might contribute to susceptibility to sPTB. This finding could be investigated as a possible genetic marker for the risk of spontaneous preterm birth.
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ABSTRACT: Interferon gamma (IFNγ) is an integral and critical molecule of the immune system, with multiple functions, mostly related to Th1 response to infection. It is critical to defence against mycobacterial infection and of increasing interest in defence against fungi. In this article, we review the genetic and epigenetic variants affecting IFNγ expression and investigate it's role in disease, with an emphasis on fungal diseases such as invasive and chronic pulmonary aspergillosis. Over 347 IFNγ gene variants have been described, in multiple ethnic populations. Many appear to confer a susceptibility to disease, especially tuberculosis and hepatitis, but also some non-infectious conditions such as aplastic anaemia, cervical cancer and psoriasis. Several epigenetic modifications are also described, increasing IFNγ expression in Th1 lymphocytes and reducing IFNγ expression in Th2 lymphocytes. Recombinant IFNγ administration is licensed for the prophylaxis of infection (bacterial and fungal) in patients with the phagocyte functional deficiency syndrome chronic granulomatous disease, although the benefits appear limited. IFNγ therapy is given to patients with profound defects in IFNγ and IL-12 production and appears to be beneficial for patients with invasive aspergillosis and cryptococcal meningitis, but the studies are not definitive. A high proportion of patients with chronic pulmonary aspergillosis are poor producers of IFNγ in response to multiple stimuli and could also benefit from IFNγ administration. The investigation and management of patients with possible or demonstrated IFNγ deficiency in adulthood is poorly studied and could be greatly enhanced with the integration of genetic data.This article is protected by copyright. All rights reserved.Immunology 07/2014; · 3.74 Impact Factor
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ABSTRACT: Objective: To investigate the association between preterm birth and cytokine genes (IFN-γ, interleukin (IL)-10) in intrauterine infection and enzyme gene (CYP1A1) in oxidative stress response. Methods: This study involved a case-control study conducted at Ewha Womans University Hospital in Seoul, Korea. Subjects with preterm deliveries (<37 weeks of gestation) and normal controls with term deliveries (≥37 weeks of gestation) were selected from gravidas who had undergone prenatal examinations in the hospital and were followed until infant delivery. The weight, height, and blood samples of each participants were obtained according to standard protocols. We included subjects who gave birth to a singleton infant and had a gestational age between 24 and 42 weeks. Mutiple births, stillbirths, and congenital anomalies were excluded. Finally, 164 gravidas with preterm births and 305 normal controls with term deliveries were enrolled in the present study. Results: Preterm delivery group and term delivery group had significant difference in gestational age and neonatal body weight (P<0.0001). There were no statistically significant association between preterm birth and IFN-γ, IL-10, CYP1A1 genes (P>0.05). Conclusion: In this study, IFN-γ (874A/T), IL-10 (1082A/G), IL-10 (819C/T), IL-10 (592A/C) and CYP1A1 (T6235C), CYP1A1 (Ile462val [A/G]) genes had no significant association with preterm birth.Korean Journal of Obstetrics and Gynecology. 01/2010; 53(7).
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ABSTRACT: Increased concentrations of tumor necrosis factor alpha (TNF-α) in blood and amniotic fluid are observed in women with preterm delivery (PTD) and TNF-α mutations at -308 position are associated with higher expression of this gene. Therefore, we compared the frequency of G308A transition in the promoter region of TNF-α gene of women and neonates delivered preterm with the normal subjects. This cross-sectional study was performed on 135 mothers who were referred for delivery. According to the gestational age, mothers and their neonates were allocated to the case (preterm, 64 subjects) and control (term, 71 subjects) groups. Using the polymerase chain reaction, restrictive fragment length polymorphism (RFLP), genotyping was performed on both maternal peripheral blood and cord blood samples to determine single nucleotide polymorphism in the promoter region of TNF-α gene at -308. Two mothers in the case group, one mother in the control group and one neonate in the case group had genotyping assays (GA) mutation. All other subjects had normal GG genotype. Frequency of GA mutation was not significantly different between two groups (P = 0.47). There is no significant association between PTD and either maternal or fetal TNF-α -308 polymorphism and frequency ofGAmutation is not significantly increased in mothers and neonates delivered preterm. It means that the presence of this mutation by itself does not modify the overall risk of PTD. Investigations on the combination of various polymorphisms indifferent genes are recommended to achieve more accurate results.International journal of preventive medicine 08/2013; 4(8):896-901.