TNF-α gene polymorphisms and expression

El-Tahan, Radwa R.; Ghoneim, Ahmed M.; El-Mashad, Noha

doi:10.1186/s40064-016-3197-y

Cited by 100 publications

(86 citation statements)

References 78 publications

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“…TNF-a coding gene (TNF) is found on chromosome 6p21.3 within the MHC region which is characterized by extremely high levels of polymorphism. TNF comprises a large number of polymorphisms, such as À238 A/G, À308 A/G, À857 C/T, and À863 A/C TNF-a promoter polymorphisms [19]. It was reported that the TNF-a-308 polymorphism is related to tuberculosis, some autoimmune disorders, and hepatocellular and breast cancers [20][21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Functionality of intrinsic disorder in tumor necrosis factor‐α and its receptors

et al. 2017

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Tumor necrosis factor-α (TNF-α) is a pleiotropic inflammatory cytokine that exerts potent cytotoxic effects on solid tumor cells, while not affecting their normal counterparts. It is also known that TNF-α exerts many of its biological functions via interaction with specific receptors. To understand the potential roles of intrinsic disorder in the functioning of this important cytokine, we explored the peculiarities of intrinsic disorder distribution in human TNF-α and its homologs from various species, ranging from zebrafish to chimpanzee. We also studied the peculiarities of intrinsic disorder distribution in human TNF-α receptors, TNFR1 and TNFR2. Analysis revealed that cytoplasmic domains of TNF-α and its receptors are expected to be highly disordered. Furthermore, although the sequence identities of analyzed TNF-α homologs range from 99.57% (between human and chimpanzee proteins) to 22.33% (between frog and fish proteins), their intrinsic disorder profiles are characterized by a remarkable similarity. These observations indicate that the peculiarities of distribution of the intrinsic disorder propensity within the amino acid sequences are evolutionary conserved, and therefore could be of functional importance for this family of proteins. We also show that disordered and flexible regions of human TNF-α and its TNFR1 and TNFR2 receptors are crucial for some of their biological activities.

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Section: Introductionmentioning

confidence: 99%

Functionality of intrinsic disorder in tumor necrosis factor‐α and its receptors

et al. 2017

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“…Some studies were showed that having an A allele at this position is associated with elevated levels of TNF-α 33 , but other studies were showed that there is no relationship between the two 34 . In addition, studies have shown that A allele is associated with lower TNF-α levels 17,35 . The expression of TNF-α, just like other cytokines is tightly regulated both at the transcriptional and post-transcriptional level.…”

Section: Discussionmentioning

confidence: 99%

“…The expression of TNF-α, just like other cytokines is tightly regulated both at the transcriptional and post-transcriptional level. The polymorphisms located within the regulatory regions of TNF-α have been reported to influence the expression and secretion of this cytokine 35 . In TNF-α -238 and -308 SNP, the presence of the A-allele increases the binding of transcription factor to the promoter region of TNF-α, thereby altering its expression 36 .…”

Section: Discussionmentioning

confidence: 99%

“…Despite the associations between TNF promoter SNPs and disease, a direct impact of TNF promoter polymorphisms upon TNF transcription has not been conclusively demonstrated. 35 It was also said that TNF-α expression may not be directly related to TNF-α promotor gene polymorphism, but requires further variation in adjacent genes. This is due to the location of the TNF-α gene close to the HLA allele.…”

Section: Discussionmentioning

confidence: 99%

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Detection of Tumor Necrosis Factor- (Tnf- ) Gene Promoters Polymorphism Among Liver Cirrhosis Patients With Chronic Hepatitis B Virus (Hbv) Infection in Surabaya, Indonesia

Wungu

Amin

Ruslan

et al. 2019

IJTID

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Polymorphisms in TNF-α gene promoter region are known of its role in the production of TNF-α which may influences the pathogenesis of liver disease. SNPs in positions 238 and 308 of TNF-α gene promoters may affect the production of these cytokines. This study was aimed to detect Single Nucleotide Polymorphism (SNP) on -238 and -308 positions in the TNF-α gene promoter among liver cirrhosis patients with HBV infection in Surabaya, Indonesia. This was descriptive exploratory research with cross sectional study design using serum liver cirrhosis patients with HBV infection in Endoscopy Outpatient Clinic Dr. Soetomo General Hospital, Surabaya from April-May 2017. SNPs at -238 and -308 on TNF-α gene promoter (rs361525 and rs1800629 respectively) were detected using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) with primers specific for the TNF-α promoter region and restriction enzymes NcoI and MspI. The genotypes of TNF-α gene promoter were assessed according to the length of the fragments produced in RFLP. Serum TNF-α levels was measured by commercial ELISA. In this study, as much as 149 positive HBsAg patients was found in Endoscopy Outpatient Clinic, Dr. Soetomo General Hospital, Surabaya. From those amount, as much as 30 liver cirrhosis patients with positive HBsAg were obtained. From 2/30 (6.7%) patients showed the GA heterozygote SNP either position -238 or -308. No patient had the AA genotype. Median blood TNF-α level in women (38 ng / L) was higher than in men (33 ng / L). TNF-α levels in patients with GA heterozygote genotype at -238 and -308 in this research was not different than wild-type (GG genotype). Among patients with liver cirrhosis due to chronic HBV infection in Surabaya, Indonesia, Surabaya, we found GA polymorphisms the TNF-α promoter gene at positions -238 and -308 in 6.7% patients, and did not find homozygous AA polymorphisms. Further studies including larger numbers of patients from various ethnic backgrounds in Indonesia are needed to provide robust data on TNF-α gene promoter polymorphisms and their role in the pathogenesis of liver cirrhosis with HBV infection in this country. ABSTRAKPolimorfisme pada promotor gen TNF-α diketahui berperan pada produksi TNF-α yang selanjutnya berperan dalam patogenesis penyakit hepar, penyakit infeksi, serta inflamasi. SNP gen TNF, terutama pada posisi 238 dan 308 dari promotor gen TNF-α telah diidentifikasi dapat memengaruhi produksi sitokin tersebut. Penelitian ini merupakan penelitian pendahuluan yang dilakukan untuk mendeteksi Single Nucleotide Polymorphism (SNP) promotor gen TNF-α posisi -238 dan -308 dari sampel penderita sirosis hati dengan infeksi VHB di Poli Endoskopi RSUD Dr. Soetomo, Surabaya. Jenis penelitian ini adalah penelitian deskriptif eksploratif laboratorik dengan rancangan penelitian cross sectional study yang mengambil sampel pasien penderita sirosis hati dengan infeksi VHB di Poli Endoskopi RSUD Dr. Soetomo Surabaya dari bulan April-Mei 2017. SNP posisi -238 dan -308 (rs361525 dan rs1800629) promotor gen...

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“…Although there is currently a lack of data in developmentally appropriate in vitro or in vivo lung models that suggest the polymorphisms impact on the levels of the specific cytokines, a number of other evidences (in non-lung models or non-in vitro/in vivo studies) strongly indicate this possibility. [18][19][20][21][22][23][24][25][26] In this study, we hypothesized that these polymorphisms, which may affect gene expression, could be associated with the risk of BPD among Han Chinese newborns, and we aimed to fill the gap in the literature by investigating the association of these 14 polymorphisms with BPD risk among Han Chinese.…”

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confidence: 99%

Association of cytokine gene polymorphisms with bronchopulmonary dysplasia in Han Chinese newborns

Chen

Zheng²

2017

Pediatric Pulmonology

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Objective: To investigate the association of 14 cytokine gene polymorphisms with bronchopulmonary dysplasia (BPD) among Han Chinese newborns. The 14 polymorphisms investigated were IL18 rs1946519, rs1946518, rs187238, rs360718, and rs360717 polymorphisms, IL10 rs3024493 polymorphism, IL6 rs1800795, rs1800796, and rs1800797 polymorphisms, TNF rs361525 and rs1800629 polymorphisms, and TGFB1 rs1800469, rs1800468, and rs1800471 polymorphisms.Working hypothesis: The polymorphisms could be associated with the risk of BPD among Han Chinese newborns.Study design, patient-subject selection, and methodology: This is a retrospective study. Genotyping of these polymorphisms were performed on BPD cases (N = 1022) and non-BPD controls (N = 1039) who were ascertained using the established Jobe and Bancalari criteria. The odds ratios (ORs) of polymorphisms whose genotype distribution in the controls fulfilled the Hardy-Weinberg equilibrium (HWE) were calculated to evaluate the strengths of genetic association.Results: Genotype distributions of IL6 rs1800795 and rs1800797 polymorphisms deviated significantly from HWE and were omitted from the analysis. Among the 12 remaining polymorphisms, only TNF rs361525 polymorphism demonstrated a statistically significant association with BPD risk. The heterozygous GA genotype of TNF rs361525 polymorphism showed an OR of 1.932 (1.512-2.470), while the homozygous AA variant genotype showed an OR of 2.927 (1.216-7.048) (P = 0.000 and P = 0.017, respectively). Besides, the allelic OR was also analyzed, and it was found that the variant A allele of TNF rs361525 polymorphism showed an OR of 2.146 (1.718-2.680) (P = 0.000).Conclusion: TNF rs361525 polymorphism could influence BPD risk among Han Chinese newborns. K E Y W O R D Sbronchopulmonary dysplasia (BPD), genetic variations, odds ratio, premature infants

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TNF-α gene polymorphisms and expression

Cited by 100 publications

References 78 publications

Functionality of intrinsic disorder in tumor necrosis factor‐α and its receptors

Functionality of intrinsic disorder in tumor necrosis factor‐α and its receptors

Detection of Tumor Necrosis Factor- (Tnf- ) Gene Promoters Polymorphism Among Liver Cirrhosis Patients With Chronic Hepatitis B Virus (Hbv) Infection in Surabaya, Indonesia

Association of cytokine gene polymorphisms with bronchopulmonary dysplasia in Han Chinese newborns

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