Associations of the PTPN22 and CTLA-4 genetic polymorphisms with Taiwanese ankylosing spondylitis.

Ankylosing spondylitis (AS) is an autoimmune disease, and the imbalance of peripheral tolerance is involved in its pathogenesis. Importantly, the negative signal of activated T cells plays a crucial role in the balance of peripheral tolerance. It has been postulated that human protein tyrosine phosphatase nonreceptor 22 (PTPN22) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) genes encode proteins that are actively involved in regulating T-cell activation. Therefore, we evaluated the effects of PTPN22 and CTLA-4 genotypes on the occurrence of AS. Genetic polymorphisms of PTPN22 -1123G/C and CTLA-4 +49A/G were identified by polymerase chain reaction for 391 AS patients and 391 healthy controls. Subjects with PTPN22 CC and GC genotypes had a greater risk of AS occurrence than those with PTPN22 GG genotype [relative risk = 1.39, 95 % confidence interval (95 % CI) 1.03-1.88]. Further, subjects with PTPN22 CC/CTLA-4 AA or PTPN22 GC/CTLA-4 AA genotypes had 1.90-fold (95 % CI 1.02-3.49) greater risk of AS development than those with other combinations of PTPN22 and CTLA-4 genotypes. Our findings indicated that PTPN22 -1123G/C and CTLA-4 +49A/G genetic polymorphisms have a combined effect on the development of AS.

Exposure to environmental tobacco smoke, human E-cadherin C-160A polymorphism, and childhood asthma.

BACKGROUND: Environmental tobacco smoke (ETS) is a risk factor for asthma. Importantly, cigarette smoke can decrease the adherence of epithelial cells and increase detachment. The adhesion molecule E-cadherin (CDH1) has an essential role in the formation of epithelial junction. Turnover of the extracellular matrix, which is characterized by airway remodeling, depends on the imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs). OBJECTIVE: To evaluate the effects of ETS exposure and CDH1, MMP-3, and TIMP-1 genetic polymorphisms on childhood asthma. METHODS: The CDH1 C-160A, MMP-3 -1171, and TIMP-1 T372C genotypes were identified by polymerase chain reaction in 299 asthmatic children and 383 healthy controls. RESULTS: More ETS exposure (>5 vs 0 cigarettes/day; odds ratio [OR], 1.45; 95% confidence interval [CI], 1.05-2.01) and the presence of CDH1 AA/CA genotypes (OR, 1.53; 95% CI, 1.08-2.17) were associated with childhood asthma. Compared with children with less ETS exposure (0-5 cigarettes/day) and the CDH1 CC genotype, those with less ETS exposure and the CDH1 AA/CA genotypes and those with more ETS exposure and the CDH1 CC genotype had a moderate risk of asthma. The greatest risk for asthma was in children with more ETS exposure and the CDH1 AA/CA genotypes (OR, 3.03; 95% CI, 1.81-5.06), and this interaction between CDH1 polymorphism and ETS exposure was significant. In addition, asthma cases with more ETS exposure or the CDH1 AA/CA genotypes had obviously increased eosinophil counts. CONCLUSION: Susceptible CDH1 genotypes might modulate the development of asthma, especially for children exposed to ETS.

Association of IL-12B genetic polymorphism with the susceptibility and disease severity of ankylosing spondylitis.

OBJECTIVE: Interleukin 23 (IL-23) stimulates the differentiation of T helper 17 (Th17) cells, which are involved in the pathogenesis of ankylosing spondylitis (AS). Binding of IL-23 to the IL-23 receptor complex activates Janus kinases 2 and tyrosine kinase 2, which phosphorylate IL-23R and subsequently promote the transcription of the IL-17 gene. IL-12B encodes a p40 subunit common to IL-12 and IL-23. We evaluated the effects of IL-12B and IL-23R genotype on the occurrence and clinical features of AS. METHODS: A total of 362 patients with AS and 362 healthy controls were enrolled in the study. Genotypes of IL-12B A1188C (rs3212227) and IL-23R C2370A (rs10889677) were identified by polymerase chain reaction/restriction fragment-length polymorphism. Disease activity and functional status were assessed by Bath AS indices. RESULTS: Subjects carrying IL-12B CC [matched relative risk (RR(m)) 1.93, 95% CI 1.23-3.03] and IL-12B AC (RR(m) 1.73, 95% CI 1.21-2.46) genotypes had a significantly greater risk of developing AS than subjects with the IL-12B AA genotype. Subjects carrying both IL-12B CC and IL-23R AA genotypes also had a significantly higher risk (RR(m) 2.98, 95% CI 1.51-5.89) of developing AS compared to those with IL-12B AA and IL-23R CC/CA genotypes, and this interaction between IL-12B and IL-23R was significant. Patients with AS who had IL-12B CC and IL-12B AC genotypes had an obviously increased Bath Ankylosing Spondylitis Disease Activity Index score compared to those who carried the IL-12B AA genotype (4.3 vs 3.7). CONCLUSION: The IL-12B A1188C genotype was associated with the development and disease severity of AS.

An OGG1 polymorphism is associated with mitochondrial DNA content in pesticide-exposed fruit growers.

Exposure to pesticides has the capacity to cause mitochondrial dysfunction. An increase mitochondrial DNA (mtDNA) content has also been suggested to relate with DNA damaging agent. In mitochondria, the manganese superoxide dismutase (MnSOD) is a scavenger of reactive oxygen species, and the 8-oxoguanine DNA glycosylase (OGG1) is the major DNA glycosylase for the repair of 8-oxoG lesions. However, the alteration of mtDNA content elicited by pesticide exposure in people with genetic variations in MnSOD or OGG1 has not been investigated. In this study, the mitochondrial to nuclear DNA ratio was quantified in the peripheral blood of 120 fruit growers who experienced pesticide exposure and 106 unexposed controls by real-time quantitative polymerase chain reaction (real-time qPCR). Questionnaires were administered to obtain demographic data and occupational history. The MnSOD and OGG1 genotypes were identified by the PCR based restriction fragment length polymorphism analysis. After adjusting for confounding effects, multiple regression model revealed that subjects experiencing high or low pesticide exposure had a greater mtDNA content than that of controls. The OGG1 Ser-Ser genotype was also associated with an increased mtDNA content. No association between MnSOD genotype and mtDNA content was revealed. Thus, subjects experiencing pesticide exposure had greater mtDNA content and the OGG1 genotype may modulate mtDNA content in pesticide-exposed fruit growers.

Sleep quality and immune mediators in asthmatic children.

BACKGROUND: Asthmatic children have been reported to complain about poor sleep quality. Recent research has demonstrated a relationship between sleep and circulating cytokines. This study aimed to assess the relationship between serum cytokine levels and sleep quality in asthmatic children. METHODS: After an initial screening phase at allergy clinic visits, 90 asthmatic children aged 6-12 years were enrolled to complete the Chinese version of the (Childhood) Asthma Control Test (ACT). A questionnaire assessing sleep quality of asthmatic children was also administered to all subjects and parents. We determined the serum levels of interleukin (IL)-4, IL-6, IL-10, IL-12, total immunoglobulin (Ig) E, and protactin at enrollment. RESULTS: Subjects with an ACT score > or =20 were assigned to the well-controlled group and those with a score of 19 were assigned to the inadequately controlled group. In the well-controlled group, good sleepers had a significantly tower mean level of IL-10 and a higher mean ratio of IL-12/IL-10 compared with the poor sleepers. Furthermore, the serum prolactin level was significantly greater in the good sleeper subgroup. In both subgroups, the concentrations of IL-6, IL-12 and total IgE were not significant different. CONCLUSION: Good sleep is associated with a lower IL-10 level, a higher prolactin concentration, and a higher IL-12/IL-10 ratio. Prolactin may have a potential role in this immunity shift. Thus, further insight into the functional role of cytokines on the sleep quality of asthma sufferers will result in the identification of novel therapeutic perspectives.

Treatment of perennial allergic rhinitis with lactic acid bacteria.

Probiotics are perceived to exert beneficial effects in the prevention and treatment of allergic diseases via modifying the gut ecosystem. The aim of this study was to assess whether ingestion of fermented milk containing Lactobacillus paracasei-33 (LP-33), a strain newly isolated from the human intestinal tract, can improve the quality of life of patients with perennial allergic rhinitis. In a randomized, double-blind, placebo-controlled trial, we gave patients fermented milk with (n = 60) or without (n = 20) the addition of LP-33 (2 x 10(9) colony-forming units per bottle) for 30 days. A modified questionnaire concerning pediatric rhinoconjunctivitis quality of life was administered to all subjects or their parents at each clinical visit. Scores for the overall quality of life significantly decreased in the LP-33 group as compared with the placebo group, in both frequency (-16.02 +/- 2.14 vs. -7.27 +/- 3.55, respectively; p = 0.037) and level of bother (-16.35 +/- 2.33 vs. -6.20 +/- 3.13, respectively; p = 0.022) after the 30-day treatment. Subjects reported no severe adverse effects such as fever, abdominal pain, or diarrhea. The results suggest that ingestion of LP-33-fortified fermented milk for 30 days can effectively and safely improve the quality of life of patients with allergic rhinitis, and may serve as an alternative treatment for allergic rhinitis.