Association of HLA-DRB1 amino acid residues with giant cell arteritis: genetic association study, meta-analysis and geo-epidemiological investigation

Introduction: Giant cell arteritis (GCA) is an autoimmune disease commonest in Northern Europe and Scandinavia. Previous studies report various associations with HLA-DRB1*04 and HLA-DRB1*01; HLA-DRB1 alleles show a gradient in population prevalence within Europe. Our aims were (1) to determine which amino acid residues within HLA-DRB1 best explained HLA-DRB1 allele susceptibility and protective effects in GCA, seen in UK data combined in meta-analysis with previously published data, and (2) to determine whether the incidence of GCA in different countries is associated with the population prevalence of the HLA-DRB1 alleles that we identified in our meta-analysis. Methods: GCA patients from the UK GCA Consortium were genotyped by using single-strand oligonucleotide polymerization, allele-specific polymerase chain reaction, and direct sequencing. Meta-analysis was used to compare and combine our results with published data, and public databases were used to identify amino acid residues that may explain observed susceptibility/protective effects. Finally, we determined the relationship of HLA-DRB1*04 population carrier frequency and latitude to GCA incidence reported in different countries. Results: In our UK data (225 cases and 1378 controls), HLA-DRB1*04 carriage was associated with GCA susceptibility (odds ratio (OR) = 2.69, P = 1.5×10 −11 ), but HLA-DRB1*01 was protective (adjusted OR = 0.55, P = 0.0046). In meta-analysis combined with 14 published studies (an additional 691 cases and 4038 controls), protective effects were seen from HLA-DR2, which comprises HLA-DRB1*15 and HLA-DRB1*16 (OR = 0.65, P = 8.2×10 −6 ) and possibly from HLA-DRB1*01 (OR = 0.73, P = 0.037). GCA incidence (n = 17 countries) was associated with population HLA-DRB1*04 allele frequency (P = 0.008; adjusted R 2 = 0.51 on univariable analysis, adjusted R 2 = 0.62 after also including latitude); latitude also made an independent contribution. Conclusions: We confirm that HLA-DRB1*04 is a GCA susceptibility allele. The susceptibility data are best explained by amino acid risk residues V, H, and H at positions 11, 13, and 33, contrary to previous suggestions of amino acids in the second hypervariable region. Worldwide, GCA incidence was independently associated both with population frequency of HLA-DRB1*04 and with latitude itself. We conclude that variation in population HLA-DRB1*04 frequency may partly explain variations in GCA incidence and that HLA-DRB1*04 may warrant investigation as a potential prognostic or predictive biomarker

Effect of Kinesiotaping Intervention on Knee Muscle Strength and Delayed Onset Muscle Soreness Pain Following Eccentric Fatigue Training

Scopu

Effects of knee osteoarthritis severity on kinematic gait parameters [Diz osteoartrit şiddetinin yürüyüşün kinematik parametreleri üzerine etkileri]

Purpose: The aim of this study was to investigate gait differences via 3-D gait analysis system through osteoarthritis progression in patients with knee osteoarthritis and compare the results with healthy individuals. Methods: According to Kellgren-Lawrence radiologic classification Grade I-II and III, a total of 45 patients (mean age: 54.02±6.58 years) with (aged between 41-65 years) bilateral knee osteoarthritis (female:36, male:9) and 14 (aged between 48-61 years) healthy individuals (mean age: 53.21 ±4.42 years; female: 12, male:2) participated in the study. Gait analysis was performed via Vicon Gait Analysis System consisted of 6 infrared cameras and 2 force platforms. Results: Knee flexion during swing phase and total knee flexion range of motion parameters were statistically lower in Grade II and III groups than the controls (p<0.008). Gait speed parameter was significantly slower in patients with Grade III group than Grade I and control groups. In addition, gait speed parameter was lower in Grade II than control groups (p<0.008). There was significant decrease in stride length parameter in Grade III group compared to Grade I and control groups (p<0.001). Discussion: Distinctive kinematic changes were decrease in knee flexion angle during swing phase, gait speed and stride length parameters in patients with knee osteoarthritis. These variations were obvious accompanying with the severity of osteoarthritis. The possible reason for decrease in knee flexion angle during swing phase was thought decrease in gait speed