Rheumatoid arthritis is a common autoimmune disease characterized by chronic inflammation. We report a meta-analysis of genome-wide association studies (GWAS) in a Japanese population including 4,074 individuals with rheumatoid arthritis (cases) and 16,891 controls, followed by a replication in 5,277 rheumatoid arthritis cases and 21,684 controls. Our study identified nine loci newly associated with rheumatoid arthritis at a threshold of P < 5.0 × 10(-8), including B3GNT2, ANXA3, CSF2, CD83, NFKBIE, ARID5B, PDE2A-ARAP1, PLD4 and PTPN2. ANXA3 was also associated with susceptibility to systemic lupus erythematosus (P = 0.0040), and B3GNT2 and ARID5B were associated with Graves' disease (P = 3.5 × 10(-4) and 2.9 × 10(-4), respectively). We conducted a multi-ancestry comparative analysis with a previous meta-analysis in individuals of European descent (5,539 rheumatoid arthritis cases and 20,169 controls). This provided evidence of shared genetic risks of rheumatoid arthritis between the populations.
The purpose of this study was to explore the occlusal force distribution on the dental arch in the intercuspal position and to evaluate the relationship between the clenching strength and the occlusal force distribution. These variables were recorded using the Dental Prescale System in 16 healthy young adults. The number of tooth contacts, occlusal force and occlusal contact area increased linearly as clenching strength increased. The distribution of the occlusal force was greatest at the molar region followed by the premolar and anterior teeth region. The proportion of occlusal force (occlusal force at each region/total occlusal force) on molar regions increased as clenching strength increased. On the contrary, the proportion of occlusal force on the premolar and anterior teeth regions decreased as clenching strength increased. These findings suggest that control of occlusal force is important in diagnosis of the nature of occlusal contacts.
Variability of R-R intervals and arterial blood pressure signals in chronically instrumented fetal lambs was analyzed by power spectral analysis based on an assumption of maximum entropy. There were four consistent components, very low (VL, 0.01-0.025 cycle/beat), low (L, 0.025-0.125 cycle/beat), middle (M, 0.125-0.2 cycle/beat), and high (H, 0.2-0.5 cycle/beat), in the normal heart rate variability and blood pressure spectra. Integrated peaks in the power spectrum were compared before and after the administration of sympathetic and parasympathetic blockades. beta-Sympathetic blockade reduced the spectral power in the VL and L frequency components. alpha-Sympathetic blockade reduced only the M frequency component in the spectrum of R-R interval variability. Parasympathetic blockade reduced the H and L frequency components in the R-R interval variability spectrum but increased these components in the systolic blood pressure variability spectrum. The results clearly demonstrate the association between fetal autonomic activity and change of power spectrum of heart rate and blood pressure variability.
IntroductionRheumatoid arthritis (RA) is a systemic, chronic inflammatory disease influenced by both genetic and environmental factors, leading to joint destruction and functional impairment. Recently, a large-scaled GWAS meta-analysis using more than 37,000 Japanese samples were conducted and 13 RA susceptibility loci were identified. However, it is not clear whether these loci have significant impact on joint destruction or not. This is the first study focused on the 13 loci to investigate independent genetic risk factors for radiographic progression in the first five years from onset of RA.MethodsSharp/van der Heijde score of hands at 5-year disease duration, which represents joint damage, were measured retrospectively and used as an outcome variable in 865 Japanese RA patients. Genetic factors regarded as putative risk factors were RA-susceptible polymorphisms identified by the Japanese GWAS meta-analysis, including HLA-DRB1 (shared epitope, SE), rs2240340 (PADI4), rs2230926 (TNFAIP3), rs3093024 (CCR6), rs11900673 (B3GNT2), rs2867461 (ANXA3), rs657075 (CSF2), rs12529514 (CD83), rs2233434 (NFKBIE), rs10821944 (ARID5B), rs3781913 (PDE2A-ARAP1), rs2841277 (PLD4) and rs2847297 (PTPN2). These putative genetic risk factors were assessed by a stepwise multiple regression analysis adjusted for possible non-genetic risk factors: autoantibody positivity (anti-citrullinated peptide antibody [ACPA] and rheumatoid factor), history of smoking, gender and age at disease onset.ResultsThe number of SE alleles (P = 0.002) and risk alleles of peptidyl arginine deiminase type IV gene (PADI4, P = 0.04) had significant impact on progressive joint destruction, as well as following non-genetic factors: ACPA positive (P = 0.0006), female sex (P = 0.006) and younger age of onset (P = 0.02).ConclusionsIn the present study, we found that PADI4 risk allele and HLA-DRB1 shared epitope are independent genetic risks for radiographic progression in Japanese rheumatoid arthritis patients. The results of this study give important knowledge of the risks on progressive joint damage in RA patients.
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