Takayasu arteritis is a rare inflammatory disease of large arteries. The etiology of Takayasu arteritis remains poorly understood, but genetic contribution to the disease pathogenesis is supported by the genetic association with HLA-B*52. We genotyped ~200,000 genetic variants in two ethnically divergent Takayasu arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. We identified and confirmed two independent susceptibility loci within the HLA region (r(2) < 0.2): HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 × 10(-16)) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 × 10(-9); and rs189754752, OR = 2.47, p = 4.22 × 10(-9)). In addition, we identified and confirmed a genetic association between Takayasu arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 × 10(-12)). The risk allele in this locus results in increased mRNA expression of FCGR2A. We also established the genetic association between IL12B and Takayasu arteritis (rs56167332, OR = 1.54, p = 2.18 × 10(-8)).
Heart rate variability (HRV) is a useful tool for the detection of sympathetic-parasympathetic balance in the autonomic nervous system. Autonomic nervous system involvement in patients with rheumatoid arthritis (RA) has rarely been studied and has shown conflicting results. Our purpose was to determine if HRV showed changes in patients with RA in comparison with the normal population. Short-term analysis of HRV was performed for time-domain frequency in 42 patients with RA and 44 matched controls. In this analysis, patients displayed lower standard deviation of the mean than healthy subjects ( P<0.0001). Patients tended to display higher pNN50 and root-mean-square of successive difference values than did healthy subjects, but these differences were not statistically significant (P >0.05). In frequency domain analysis, the spectral measures of HRV showed reduced high-frequency (HF) values and an higher low-frequency (LF) values; as a result, the ratio between low and high frequencies (LF/HF), representative of sympathovagal modulation, was significantly increased (P=0.001, P=0.012, and P=0.003, respectively). Our data suggest an increase in sympathetic control of the heart rate in patients with RA. This increased sympathetic activity could play a key role in the development of ventricular tachyarrhythmias in RA and may be related to the higher incidence of sudden death in this disorder.
It is suggested that higher serum Lp(a), lower HDL-C, higher TG level, and a high ratio of TC/HDL-C might show high risk of atherosclerosis. Inflammation in RA may cause changes in HDL-C and Lp(a) metabolisms.
Objective Takayasu’s arteritis is a rare large vessel vasculitis with incompletely understood etiology. We performed the first unbiased genome-wide association study (GWAS) in Takayasu’s arteritis. Methods Two independent Takayasu’s arteritis cohorts from Turkey and North America were included in our study. The Turkish cohort consisted of 559 patients and 489 controls, and the North American cohort consisted of 134 European-derived patients and 1,047 controls. Genotyping was performed using the Omni1-Quad and Omni2.5 genotyping arrays. Genotyping data were subjected to rigorous quality control measures and subsequently analyzed to discover genetic susceptibility loci for Takayasu’s arteritis. Results We identified genetic susceptibility loci for Takayasu’s arteritis with a genome-wide level of significance in IL6 (rs2069837, OR= 2.07, P= 6.70×10−9), RPS9/LILRB3 (rs11666543, OR= 1.65, P= 2.34×10−8), and an intergenic locus on chromosome 21q22 (rs2836878, OR= 1.79, P= 3.62×10−10). The genetic susceptibility locus in RPS9/LILRB3 is located within the leukocyte receptor complex (LRC) gene cluster on chromosome 19q13.4, and the disease risk variant in this locus correlates with reduced expression of multiple genes including the inhibitory leukocyte immunoglobulin-like receptor gene LILRB3 (P= 2.29×10−8). In addition, we identified candidate susceptibility genes with suggestive levels of association (P <1×10−5) including PCSK5, LILRA3, PPM1G/NRBP1, and PTK2B in Takayasu’s arteritis. Conclusion This study identified novel genetic susceptibility loci for Takayasu’s arteritis and uncovered potentially important aspects in the pathophysiology of this form of vasculitis.
Changes in liver biochemical test results have been described in hyperthyroid patients before and after antithyroid therapy. In the present study, we analyzed liver tests at diagnosis and after 6 weeks of treatment with propylthiouracil (PTU) in 43 patients with hyperthyroidism. At diagnosis, 60.5% of the patients had at least one liver abnormality. Elevations of alkaline phosphatase, alanine and aspartate aminotransferase, and gamma-glutamyl transpeptidase levels were observed in 19 (44.2%), 10 (23.3%), six (14%), and six (14%) of the patients, respectively. At the end of the 6-week treatment with PTU, elevations in liver test values, possibly induced by PTU, were found in seven (16.3%) patients. Age, sex, type of goiter (either diffuse or multinodular), and presence or absence of abnormal liver biochemical tests at diagnosis were not significant in determining the possibility of PTU-induced elevations in liver tests. These data suggest that liver test abnormalities are frequently found at the time of diagnosis of hyperthyroidism. However, the presence or absence of these abnormalities does not predict elevations in liver test results, which are possibly induced by PTU during therapy.
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