A functional polymorphism in the promoter region of TLR3 is associated with susceptibility to end-stage renal disease.

BACKGROUND/AIMS: End-stage renal disease (ESRD) is simultaneously associated with immune activation, systemic inflammation and immune deficiency. Toll-like receptor 3 (TLR3), a receptor for viral double-stranded RNA, is involved in immune cell activation in renal diseases and may contribute to chronic inflammatory disease progression. To date, effects of TLR3 polymorphisms on ESRD remain unknown. Therefore, we determined the predictive value of TLR3 polymorphisms and further functionally studied ESRD. METHODS: We performed a case-control association study and genotyped 616 ESRD patients and 813 healthy controls. Patients were genotyped for -7C/A, 1377C/T and 1234C/T polymorphisms of TLR3 using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The Haplotype association analysis was performed using the Haploview package. A luciferase reporter assay and real-time PCR were used to test the function of the -7C/A promoter polymorphism in TLR3 expression in human embryonic kidney 293 (HEK293) cells. RESULTS: Genotype distributions of -7C/A and 1377C/T in TLR3 were significantly different in ESRD patients and healthy controls. The ATC haplotype of TLR3 was associated with a decreased risk of ESRD. We also found significant differences in TLR3 expression by dexamethasone treatment between various genotypes of -7C/A (p = 0.02). TLR3 transcriptional activity of the variant -7 C allele was higher than that of the -7 A allele after dexamethasone treatment. CONCLUSION: RESULTS indicate that, in our population, the presence of the C allele of -7C/A in TLR3 increases the susceptibility to ESRD. In vitro studies demonstrated that -7C/A may be involved in ESRD development through transcriptional modulation of TLR3.

Gender differences between WOMAC index scores, health-related quality of life and physical performance in an elderly Taiwanese population with knee osteoarthritis.

OBJECTIVE: To investigate the importance of the WOMAC index score, health-related quality of life and physical performance in each domain affected by knee osteoarthritis (OA) and to identify gender differences in the importance of these domains and physical performances. MATERIAL AND METHODS: We performed a population-based study for radiographic knee OA among participants aged more than 65 years. Demographic data were collected and anthropometric measurement, radiographic assessment, the WOMAC index score, the short-form 12 (SF-12), the Timed and Up to Go Test (TUGT) and the Five Times Sit to Stand Test (FTSST) were performed. RESULT: There were 901 individuals (409 males and 492 females) aged 74.04±6.92 (male: 76.35±7.33; female: 72.12±5.92) years included in this study. The WOMAC scores of participants with OA were higher than those without OA in males and females (male: 11.97±15.79 vs 8.23±12.84, p<0.001; female: 10.61±14.97 vs 7.59±3.31, p=0.032). The physical component summary (PCS) score was only significant in females with knee OA (62.14±24.66 vs 66.59±23.85, p=0.043), while the mental component summary (MCS) score was only significant in males with knee OA (78.02±18.59 vs 81.98±15.46, p=0.02). The TUGT and FTSST were not significant in individuals with and without OA in males and females. Moreover, the multivariate results for the WOMAC score were significant for females (3.928 (95% CI 1.287 to 6.569), p=0.004). CONCLUSIONS: The PCS domains of SF-12 and MCS domains of SF-12 are crucial in Taiwanese females and elderly males, respectively, with knee OA. Different evaluation and treatment strategies based on gender differences should be considered in elderly Taiwanese patients with knee OA to improve their quality of life.