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Introduction: Rheumatoid arthritis (RA) is a chronic inflammation disease that may involve extra-articular organs in addition to joints. Many proinflammatory cytokines are involved in the inflammatory process of RA. IkappaBalpha conjugates with NF-kappaB and is a key player in regulation of the inflammatory process. We carried out experiments to define the effect of different promoter polymorphisms on the transcriptional activities of IkappaBalpha promoter and the development of RA., Methods: Different IkappaBalpha promoter reporters were constructed and were examined in human mononuclear cells, THP-1 cells. One hundred forty patients and 115 healthy controls were recruited from the Kaohsiung Medical University Hospital., Results: The activities of IkappaBalpha promoter constructs with -826C, -550A, -519T, and -826T, -550A, -519T genotypes were expressed at one half the activity level of other constructs. Promoter constructs containing the sites -550A/T and -519T had a reduced risk of rheumatoid arthritis. The odds ratio of -826C/T genotype was significantly associated with an increase of risk in causing rheumatoid arthritis, whereas -826T/T genotype was associated only with a slightly increased risk of RA, but without statistical significance (odds ratio = 1.2; 95% confidence interval, 0.4-3.8)., Conclusion: The increase of T allele was associated with a significant increased risk and the tendency to the pathogenesis of RA. The association between IkappaBalpha promoter polymorphisms and disease severity of rheumatoid arthritis is partly due to different transcriptional activities of IkappaBalpha promoter and the activation of NF-kappaB.

Although cooking emission from high-temperature frying has been deemed a Group 2A carcinogen by the International Agency for Research on Cancer, little is known about its impact on cervical tumorigenesis. To investigate the precancerous consequence of cooking oil fumes on cervical intraepithelial neoplasm (CIN), a community-based case-control study, which takes all known risk factors into consideration, was conducted in Taiwan. From 2003 to 2008, in a Pap smear screening and biopsy examination network, 206 pathology-verified women with inflammations/atypical squamous cells of undetermined significance or CIN grade-1 (CIN1) and 73 with CIN2-3 (defined as low-grade squamous intraepithelial lesions (LGSIL) and high-grade squamous intraepithelial lesions (HGSIL), respectively); and 1,200 area-and-age-matched controls with negative cytology were recruited. Multinomial logistic regression was applied in the multivariate analysis to determine the likelihood of contracting LGSIL or HGSIL. The risks of the two lesions increased with the increase of carcinogenic high-risk human papillomavirus DNA load, with a clear dose-response relationship. Chefs were observed to experience a 7.9-fold elevated HGSIL risk. Kitchens with poor fume ventilation during the main cooking life-stage correlated to a 3.7-fold risk of HGSIL, but not for LGSIL. More than 1 hr of daily cooking in kitchens with poor fume conditions appeared to confer an 8.4-fold HGSIL risk, with an 8.3-fold heterogeneously higher odds ratio than that (aOR = 1.0) for LGSIL. Similar risk pattern has been reproduced among never-smoking women. Our findings demonstrate the association between indoor exposure to cooking fumes from heated oil and the late development of cervical precancerous lesions. This final conclusion needs to be verified by future research.

To investigate the role of IkappaBalpha promoter polymorphisms in the development of Behçet's disease, eighty-six patients with Behçet's disease and 120 healthy controls were enrolled in this study. The IkappaBalpha -881A/G, -826C/T, -550A/T, -519C/T, and -297C/T polymorphisms were measured by the method of polymerase chain reaction/ restriction fragment length polymorphism. This study demonstrated that the genotype frequencies of IkappaBalpha -826C/T and -826T/T were significantly higher in the patients with Behçet's disease than in the controls. Both in the dominant and in the recessive models, the patients with Behçet's disease have higher frequencies of the IkappaBalpha -826T containing genotype than the controls. The allele frequency of IkappaBalpha -826T was significantly increased in the patients with Behçet's disease. The frequencies of the IkappaBalpha -881A -826T -550A -519C -297C and IkappaBalpha -881A -826T -550A -519T -297C haplotypes were significantly higher in the patients with Behçet's disease than in the controls. In contrast, the haplotype frequency of IkappaBalpha -881A -826C -550A -519C -297C in the patients with Behçet's disease was significantly decreased. This study also revealed that the Behçet's disease patients with IkappaBalpha -826T/T have higher prevalence of skin lesions than those without IkappaBalpha -826T/T. In summary, the IkappaBalpha -826T allele, IkappaBalpha -881A -826T -550A -519C -297C and IkappaBalpha -881A -826T -550A -519T -297C haplotypes might be associated with susceptibility to Behçet's disease. The IkappaBalpha -826T/T genotype was related to the development of skin lesions in the patients with Behçet's disease.

The purpose of this study is to investigate the association of IκBα with the development of ankylosing spondylitis (AS) in Taiwan. One hundred and fifty-four patients with AS and 112 unrelated healthy controls were enrolled in this study. The IκBα-881A/G, -826C/T, -550A/T, -519C/T, and -297C/T polymorphisms were determined by the polymerase chain reaction/restriction fragment length polymorphism method. This study demonstrated that the genotype frequencies of IκBα-826C/T and -826T/T, and allele frequencies of IκBα-826T were significantly higher in the patients with AS than in the controls. We also found that the estimated haplotype frequencies of IκBα-881A -826T -550A -519C -297C and IκBα-881A -826C -550A -519T -297C were significantly increased in the patient with AS in comparison with that of the controls. In contrast, the estimated haplotype frequency of IκBα-881A -826C -550A -519C -297C was significantly decreased in the patients with AS. This study demonstrates that IκBα-826T is associated with the development of AS. Furthermore, the IκBα-881A -826T -550A -519C -297C and IκBα-881A -826C -550A -519T -297C haplotypes are related to susceptibility to AS in Taiwan.

Introduction: To investigate the association of IkBalpha promoter polymorphisms with the development of primary Sjögren's syndrome in Taiwan, 98 patients with primary Sjögren's syndrome and 110 unrelated healthy controls were enrolled in this study., Materials and Methods: The IkappaBalpha -881 A/G, IkappaBalpha -826 C/T, IkappaBalpha -550 A/T, IkappaBalpha -519 C/T, and IkappaBalpha -297 C/T polymorphisms were determined by the methods of polymerase chain reaction/restriction fragment length polymorphism., Results: This study demonstrated that the genotype frequencies of IkappaBalpha -826 C/T and IkappaBalpha -826 T/T, in comparison with that of IkappaBalpha -826 C/C, were significantly higher in the patients with primary Sjögren's syndrome than in the controls. The allele frequency of IkappaBalpha -881 G was significantly decreased in the patients with primary Sjögren's syndrome compared with that of the controls. In contrast, the allele frequency of IkappaBalpha -826 T was significantly higher in the patients with primary Sjögren's syndrome than in the controls. The similar findings could also be found in the allele carriage frequencies. The patients with primary Sjögren's syndrome had lower allele carriage frequencies of IkappaBalpha -881 G and IkappaBalpha -826 C, and a higher allele carriage frequency of IkappaBalpha -826 T. We also found that the estimated haplotype frequency of IkappaBalpha -881A-826T-550A-519C-297C was significantly increased in the patients with primary Sjögren's syndrome in comparison with that of the controls., Discussion: This study demonstrated that the IkBalpha -826T allele and IkBalpha -881A-826T-550A-519C-297C haplotype were associated with susceptibility to primary Sjögren's syndrome in Taiwan. However, these findings may not be disease-specific but may be related to inflammatory responses.

To investigate the associations of IkappaBalpha gene polymorphisms with the development and clinical manifestations of systemic lupus erythematosus (SLE), 110 patients with SLE and 120 unrelated healthy controls were enrolled in this study. The IkappaBalpha -881 A/G, -826 C/T, -550 A/T, -519 C/T, and -297 C/T polymorphisms were determined by the polymerase chain reaction/reaction fragment length polymorphism method. The genotype frequency of IkappaBalpha -826 C/T in the patients with SLE was significantly higher than that of the controls (p = 0.003, OR = 2.2, 95% CI = 1.3-3.9). The SLE patients also have significantly higher carriage rate of IkappaBalpha -826 T than the controls (p = 0.01, OR = 2.0, 95% CI = 1.2-3.4). We also found that the estimated haplotype frequency of IkappaBalpha -881A -826T -550A -519C -297C was significantly increased in the patients with SLE in comparison with that of the controls. This study also demonstrated that the association of IkappaBalpha -826 T with SLE was independent of HLA-DR15, which is associated with susceptibility to SLE in Taiwan. Moreover, a synergistic effect could also be found between IkappaBalpha -826 T and HLA-DR15. IkappaBalpha -826 T is associated with the development of SLE in Taiwan. The IkappaBalpha -881A -826T -550A -519C -297C haplotype is also associated with susceptibility to SLE. This study also demonstrated that IkappaBalpha -881G was associated with the occurrence of vasculitis in SLE patients. IkappaBalpha -550T might be a protective factor for the development of malar rash.

To investigate the role of ligands for programmed cell death 1 (PD-L) in the pathogenesis of rheumatoid arthritis (RA), 129 patients with RA and 125 unrelated healthy controls were enrolled in this study. The PD-L1 and PD-L2 polymorphisms were determined by the method of polymerase chain reaction (PCR)/direct sequencing or PCR/reaction fragment length polymorphisms. The genotype distributions of PD-L1 6777 C/G were not significantly different between the patients with RA and healthy controls. There was also no significant difference in the allele frequencies of PD-L1 6777 C/G polymorphisms between the patients with RA and controls. Similar findings could also be found in the phenotypes and alleles frequencies of PD-L2 47103 C/T and 47139 T/C polymorphisms between the patients with RA and controls. The patients with PD-L1 6777 G had higher prevalence of rheumatoid nodule in comparison with those without PD-L1 6777 G (p = 0.005, OR = 4.0, 95% CI = 1.5-10.9). In contrast, the PD-L2 47103 C/T and 47139 T/C polymorphisms were not related to the occurrence of rheumatoid nodule. This study demonstrated that the PD-L1 and PD-L2 polymorphisms were not associated with susceptibility to RA in Taiwan. PD-L1 6777 G was associated with the prevalence of rheumatoid nodule.

Human papillomavirus (HPV) infection is a high-risk factor for cervical intraepithelial neoplasm (CIN) but the association between the quantitative HPV DNA load and the severity of CIN remains controversial. We conducted a community study to investigate the correlation between the two. Potential study subjects were selected through Pap smear screening in Kaohsiung County, Taiwan. Ninety-one subjects with either their first case of inflammation or > or =CIN1 by biopsy confirmation were assigned to a case group; 175 normal subjects with negative findings by Pap smears or biopsies were assigned to a control group. Cervical HPV load was detected with Hybrid Capture II assay for high-risk HPV infection, with nested PCR for high- and low-risk HPV infection, and with type-specific PCR for HPV type 16 (HPV-16). Individuals with positive high-risk HPV infection had an increased risk of developing CIN. Compared with HPV-negative subjects, the odds ratios were 32.2 [95% confidence interval (95% CI), 10.4-99.5] for subjects with CIN1, 37.2 (95% CI, 7.4-187.6) for subjects with CIN2, and 68.3 (95% CI, 14.1-328.5) for subjects with > or =CIN3 after adjusting for other confounding factors. The similar trend was also found among the HPV-16-negative individuals. In addition, high-risk HPV DNA load levels were highly correlated with the different grades of CINs in the overall population (Spearman's correlation coefficient r = 0.67, P < 0.0001, n = 266) and the HPV-16-negative population (Spearman's correlation coefficient r = 0.58, P < 0.0001, n = 234). We concluded that high-risk HPV infection, irrespective of HPV-16 infection, was highly and positively associated with the development of CIN.