Analysis of TNF-α (-308) polymorphism and gingival crevicular fluid TNF-α levels in aggressive and chronic periodontitis: A preliminary report.

OBJECTIVES: The purpose of this study was to determine the differences in the distribution of TNF-α (-308) gene polymorphism among aggressive periodontitis, chronic periodontitis and periodontally healthy individuals and also to investigate whether this polymorphism is associated with gingival crevicular fluid TNF-α levels and periodontal disease severity. MATERIAL AND METHODS: A total of 93 individuals were enrolled in the study including 38 aggressive periodontitis, 29 chronic periodontitis patients, and 26 healthy controls. Single nucleotide polymorphism at TNF-α (-308) is analyzed by PCR-RFLP method. Gingival crevicular fluid samples were analyzed for TNF-α, using ELISA. RESULTS: The distribution of genotypes and allele frequencies for TNF-α (-308) were similar among the groups. After stratification of patients with respect to attachment level, aggressive periodontitis patients with clinical attachment level ⩾4mm was observed to have a higher frequency of TNF-α (-308) allele 2 compared to the chronic periodontitis patients with clinical attachment level ⩾4mm. No significant differences were found between the TNF-α levels of the different genotypes in spite of an insignificant increase in patient groups carrying TNF-α (-308) allele 2. CONCLUSION: The results of this study revealed an association between TNF-α (-308) allele 2 frequency and aggressive periodontitis patients with clinical attachment level ⩾4mm in the population studied.

Association of tumour necrosis factor-alpha -308 G/A polymorphism with primary open-angle glaucoma.

BACKGROUND: Tumour necrosis factor-alpha (TNF-α) is an important proinflammatory cytokine driving axonal degeneration and retinal ganglion cell apoptosis in glaucoma. The aim of the study was to evaluate the association of TNF-α -308 G/A and -238 G/A polymorphisms with primary open-angle glaucoma (POAG). DESIGN: A prospective, case-control study, university hospital setting. PARTICIPANTS: Eighty-six POAG patients and 193 healthy unrelated controls. METHODS: TNF-α polymorphisms were screened by using direct gene sequencing. MAIN OUTCOME MEASURES: Frequency of TNF-α -308 G/A and TNF-α -238 G/A promoter polymorphisms in glaucoma and healthy subjects. RESULTS: The frequencies of TNF-α -308 GA genotype and 'A' allele were higher in patients with POAG (22.1% and 12.2%, respectively) in comparison with the control group (10.9% and 6%, respectively) (P = 0.046 and 0.02, respectively), with odds ratios of 2.45 (P = 0.01, 95% CI = 1.23-4.87) and 2.19 (P = 0.013, 95% CI = 1.18-4.08), respectively. Genotype distribution of the TNF-α -238 variants did not yield a statistically significant difference between the two groups (P = 0.87). CONCLUSION: TNF-α -308 G/A polymorphism seems to be associated with POAG in Turkish population. However, population-based studies with large number of subjects and long-term follow-up are needed to verify the association of TNF-α -308 G/A polymorphism with glaucoma susceptibility.

Tumor necrosis factor alpha-308 gene polymorphism in patients with anorexia nervosa.

Tumor necrosis factor alpha (TNF-alpha) is a principal cytokine that may induce weight loss. TNF-alpha -308 G to A polymorphism increases transcription of TNF-alpha in vitro. The aim of this study was to investigate whether TNF-alpha gene promoter polymorphism at position -308 (G to A substitution) is one of the factors playing a role in the development of anorexia nervosa (AN). Sixteen patients with AN, aged 11-20 years, were included in this study, and 5/16 (31%) patients had TNF-alpha -308 G/A genotype. In the control group, 12/174 (7%) had -308 G/A genotype. There was a significant statistical difference between the patient and control groups (p=0.007). The minimum body mass index (BMI) values ever recorded for each patient during the course of the disease were significantly higher in the five patients with TNF-alpha -308 G to A polymorphism (p= 0.003). TNF-alpha gene promoter polymorphism at position -308 might be associated with a predisposition to AN and initiate the disease. The protective mechanisms that affect clinical manifestation of the disease may be related with other anti-inflammatory cytokines or immunologic mechanisms.

A novel mutation leading to a deletion in the SH3 domain of Bruton's tyrosine kinase.

X-linked agammaglobulinemia (XLA) is a primary B cell immunodeficiency disorder, caused by a defect in the Bruton tyrosine kinase (BTK) gene. Here, we describe a novel four base pair mutation (838delGAGT) in intron 9 of the BTK gene leading to the skipping of exon 9 in a 2.5-year-old boy with this disorder.

Determination of tear and serum inflammatory cytokines in patients with rosacea using multiplex bead technology.

PURPOSE: To compare serum and tear inflammatory and anti-inflammatory cytokine levels of rosacea patients with the healthy controls and evaluate the correlation of tear cytokine levels with tear function parameters. METHODS: Tear and serum interleukin (IL)-1α, IL-6, IL-8, IL-10, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF) levels were measured using multiplex bead (Luminex) technology in 12 rosacea patients without ocular involvement (group 1), 20 rosacea patients with ocular involvement (group 2), and 22 healthy subjects (group 3). The correlation of the cytokines with tear function parameters was analyzed using Spearman correlation test. RESULTS: Tear IL-10 and VEGF levels were significantly lower in group 1 (median: 35.78 pg/mL and 427.29, respectively) and group 2 (median: 26.25 pg/mL and 348.31, respectively) than in group 3 (median: 75.96 pg/mL and 480.12, respectively) (p < 0.05). Mean serum IL-8 level was significantly lower in group 2 (median = 0) compared to group 3 (median = 3.98) (p = 0.02). Tear breakup time was found to be positively correlated with IL-10 (r = 0.46, p = 0.013) and inversely correlated with MCP-1 (r = -0.52, p = 0.004). CONCLUSIONS: Tear and serum levels of cytokines and growth factors measured with Luminex technology showed a large variation in rosacea and healthy subjects. Decreased levels of tear IL-10, an anti-inflammatory cytokine, may lead to an inflammatory ocular surface environment, exacerbate ocular surface inflammation, and deteriorate tear function tests. A bigger sample size, including rosacea patients with corneal involvement, is needed to confirm the role of cytokines in the pathogenesis of rosacea-associated ocular inflammation.

Recurrent Salmonella bacteremia in interleukin-12 receptor beta1 deficiency.

Interleukin-12 receptor beta1 IL12RB1 deficiency causes vulnerability to poorly virulent mycobacteria and nontyphoid Salmonella species. We describe a 2.5 year-old girl with IL12RB1 deficiency, caused by a homozygous mutation in this gene, who presented with recurrent bacteremia caused by Salmonella spp.