Family history of rheumatic diseases in patients with rheumatoid arthritis: a large scale cross-sectional study / 北京大学学报(医学版)

OBJECTIVE@#To determine the associations between the family history of rheumatic diseases and clinical features in patients with rheumatoid arthritis (RA).@*METHODS@#In total, eight hundred and ninety patients with RA were enrolled. The demographic and clinical data were collected, including gender, age, height, body weight, age of disease onset, history of smoking and drinking, family history of rheumatic diseases, clinical and laboratory features, pain and global visual analogue scale (VAS), and multi-dimensional health assessment questionnaire (MDHAQ). Finally, 803 patients were completed the dataset and were included in the study.@*RESULTS@#In this cohort, the male/female ratio was 1:3.5, and the age of onset was (45.09±14.50) years. A total of 123 (15.32%) patients were accompanied with family history of rheumatic diseases, including RA, spondyloarthritis, Sjögren's syndrome, systemic lupus erythematosus and systemic sclerosis. The percentages of first degree, second degree and both first and second degree relatives were 91 (73.98%), 22 (17.89%), and 10 (8.13%) respectively. The most common disease was RA (70.73%), followed by other rheumatic diseases (21.95%), and RA combined with other rheumatic diseases (7.32%). The clinical and laboratory characteristics were compared between the patients with and without family history. The onset-age of the subjects was significantly different between those with and without family history of rheumatic diseases (39.97 ±13.68 vs. 46.01±14.46; P<0.01), which meant that the onset-age in patients with family history was 6.04 years earlier than that in patients without family history. The patients with family history had higher positive rate of rheumatoid factor (RF) compared with those without family history (78.48% vs. 66.67%, P<0.05). By adjusting with gender, body mass index (BMI), smoking and alcohol drinking, anti-cyclic citrullinated peptide (CCP) antibody and RF level, the age at disease onset in the patients with family history was 4.54 years earlier than that in the patients without family history (β=-4.54; 95%CI:-8.70, -0.38; P<0.05). Further hierarchical regression analysis showed that, the age at onset of the RA patients with family history was 10.02 years earlier than that without family history among the smoking patients (β= -10.02; 95%CI:-17.60, -2.43; P=0.01), while the age at onset of the RA patients with family history was 3.27 years earlier than that without family history among the never smoking patients (β=-3.27; 95%CI:-8.37, 1.82; P=0.21).@*CONCLUSION@#The family history of rheumatic diseases is a risk factor for early onset of RA, and may interact with smoking.

Gene Polymorphism Is not Associated with Rheumatoid Arthritis Susceptibility in the Northern Chinese Han Population: A Case-Control Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Interleukin (IL)-37, also called IL1F7, is a natural inhibitor of inflammatory and immune responses. It is involved in the pathogenesis of rheumatoid arthritis (RA). This study aimed to investigate the role of IL1F7 gene polymorphism in RA susceptibility in a large cohort of patients.</p><p><b>METHODS</b>Five selected single-nucleotide polymorphisms in IL1F7 genes (rs2723186, rs3811046, rs4241122, rs4364030, and rs4392270) were genotyped by TaqMan Allelic Discrimination in Northern Chinese Han population. The allele and the genotype were compared between patients with RA and healthy controls. Association analyses were performed on the entire data set and on different RA subsets based on the status of the anti-cyclic citrullinated peptide antibody and the rheumatoid factor by logistic regression, adjusting for age and gender.</p><p><b>RESULTS</b>Trend associations were detected between rs2723186, rs4241122, rs4392270, and RA in Stage I (160 patients with RA; 252 healthy controls). Further validation in Stage II comprised 730 unrelated patients with RA (mean age: 54.9 ± 12.6 years; 81.6% females) and 778 unrelated healthy individuals (mean age: 53.5 ± 15.7 years; 79.5% females). No significant differences in the distributions of alleles and genotypes were observed between the case and control groups in both the entire set and the different RA subsets. Disease activity and age of RA onset were also not associated with genotype distributions.</p><p><b>CONCLUSION</b>IL1F7 gene polymorphism does not significantly influence RA susceptibility in the Northern Chinese Han population.</p>

Gene Polymorphism Is not Associated with Rheumatoid Arthritis Susceptibility in the Northern Chinese Han Population: A Case-Control Study / 中华医学杂志(英文版)

BACKGROUND@#Interleukin (IL)-37, also called IL1F7, is a natural inhibitor of inflammatory and immune responses. It is involved in the pathogenesis of rheumatoid arthritis (RA). This study aimed to investigate the role of IL1F7 gene polymorphism in RA susceptibility in a large cohort of patients.@*METHODS@#Five selected single-nucleotide polymorphisms in IL1F7 genes (rs2723186, rs3811046, rs4241122, rs4364030, and rs4392270) were genotyped by TaqMan Allelic Discrimination in Northern Chinese Han population. The allele and the genotype were compared between patients with RA and healthy controls. Association analyses were performed on the entire data set and on different RA subsets based on the status of the anti-cyclic citrullinated peptide antibody and the rheumatoid factor by logistic regression, adjusting for age and gender.@*RESULTS@#Trend associations were detected between rs2723186, rs4241122, rs4392270, and RA in Stage I (160 patients with RA; 252 healthy controls). Further validation in Stage II comprised 730 unrelated patients with RA (mean age: 54.9 ± 12.6 years; 81.6% females) and 778 unrelated healthy individuals (mean age: 53.5 ± 15.7 years; 79.5% females). No significant differences in the distributions of alleles and genotypes were observed between the case and control groups in both the entire set and the different RA subsets. Disease activity and age of RA onset were also not associated with genotype distributions.@*CONCLUSION@#IL1F7 gene polymorphism does not significantly influence RA susceptibility in the Northern Chinese Han population.

Gender differences are associated with the clinical features of systemic lupus erythematosus / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Systemic lupus erythematosus (SLE) mostly occurred in young women. This study was undertaken to investigate the different clinical characteristics of SLE between male and female patients, and to identify the sex hormone levels and clinical outcomes of different gender in SLE patients.</p><p><b>METHODS</b>Of the 516 SLE patients admitted to the Peking University People's Hospital from January 2008 to December 2010, 58 were male and 458 were female. Clinical manifestations, laboratory profiles and disease activity scores were evaluated in male and female patients. Sex hormones levels were also compared among male patients.</p><p><b>RESULTS</b>The median age at SLE onset in male and female patients was 27.2 and 28.6 years, respectively. Compared with female patients, at onset of SLE, male patients showed higher rates of serious renal disease (58.6% vs. 47.2%, P = 0.064), neuropsychiatric SLE (20.7% vs. 12.0%, P = 0.055), and a higher incidence of anti-ds-DNA (25.9% vs. 16.8%, P = 0.069), anti-Sm (17.2% vs. 8.7%, P = 0.002), anti-Ro (46.6% vs. 28.4%, P = 0.004), anti-U1RNP (29.3% vs. 15.3%, P = 0.010), anticardiolipin antibody (25.9% vs. 11.4%, P = 0.004), and decreased C3 levels (67.2% vs. 49.8%, P = 0.009). Systemic lupus erythematosus disease activity index (SLEDAI) scores were higher in men than in women (16.8 vs. 12.8, P = 0.038). Of the 58 male patients, 24 had not received aggressive treatment during the three months prior to the study. Levels of testosterone and dihydroepiandrosterone (DHEA) were lower in male SLE patients than in male healthy controls (P = 0.004 and P = 0.006, respectively). Low serum testosterone was an independent risk factor for the development of lupus nephritis (P = 0.043). Male patients with elevated serum prolactin were at increased risk of developing neuropsychiatric manifestations of SLE (P = 0.081).</p><p><b>CONCLUSION</b>Early recognition of risk factors and appropriate intervention are essential, which might lead to high disease activity and serious systemic damage in male SLE patients.</p>

Macrophage-inducible C-type lectin is associated with anti-cyclic citrullinated peptide antibodies-positive rheumatoid arthritis in men / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Macrophage-inducible C-type lectin (MINCLE) is an important member of C-type lectin superfamily, which has been shown evidence for susceptibility to arthritis in animal models. We aimed to investigate the possible association of MINCLE with rheumatoid arthritis (RA) susceptibility in Chinese Han population.</p><p><b>METHODS</b>Haplotypes from HapMap database (Chinese Han Beijing, CHB) were used to select tag-single nucleotide polymorphism (SNP) (r(2) = 0.8) residing in MINCLE gene. A total of 563 patients with RA and 404 healthy controls were TagMan genotyped for SNP rs10841845. Association analyses were performed on the whole data set and on RA subsets based on gender difference and the status of anti-cyclic citrullinated peptide (anti-CCP) antibody in RA patients. Association statistics were calculated by age and sex adjusted logistic regression.</p><p><b>RESULTS</b>Overall, MINCLE SNP rs10841845 was not associated with susceptibility to RA. However, following anti-CCP stratification, rs10841845 GG genotypes conferred a significantly protective effects against anti-CCP-positive RA (OR 0.65, 95%CI 0.430 - 0.995, P = 0.048). Following gender stratification, SNP rs10841845 G allele appeared to insert its RA protective effect only in male patients, both at allele level (G vs. A OR 0.66, 95%CI 0.46 - 0.93, P = 0.018) and at genotype level (GG vs. AA+AG, OR 0.429, 95%CI 0.20 - 0.95, P = 0.036). Notably, the male RA protective effect of rs10841845 G allele was only seen in anti-CCP-positive RA (G vs. A: OR 0.64, 95%CI 0.43 - 0.96, P = 0.029; GG vs. AA+AG: OR 0.375, 95%CI 0.14 - 0.94, P = 0.038). Furthermore, we observed a significant reduction of Disease Activity Score (DAS) 28 score (3.91 ± 0.70 vs. 5.66 ± 0.31, P = 0.022) and serum C-reactive protein levels (31.64 ± 24.13 vs. 91.80 ± 12.02, P = 0.012) in male anti-CCP-positive RA patients carrying rs10841845 GG genotype, compared with patients carrying AA+AG genotypes.</p><p><b>CONCLUSIONS</b>Our study provides the evidence for a gender specific association between MINCLE rs10841845 and RA susceptibility. The SNP rs10841845 G allele appears to have protective effect against anti-CCP-positive RA and confer reduced RA activity in men.</p>

Serum IgA against type 3 muscarinic acetylcholine receptor is a novel marker in diagnosis of Sjögren's syndrome / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Antibodies against type 3 muscarinic acetylcholine receptor (M3R) are involved in the pathogenesis of Sjögren's syndrome (SS), but the clinical value of them in SS patients has been controversial. The aims of this study were to: (1) establish an improved enzyme-linked immunosorbent assay (ELISA) to detect IgA antibodies against M3R; (2) evaluate the value of IgA antibodies against the second extracellular loop of M3R205-220 (c2M3RP) in diagnosis of SS.</p><p><b>METHODS</b>To increase the ELISA sensitivity, c2M3RP was coupled to bovine serum albumin (BSA) by the glutaraldehyde method and a 96-well microplate was treated by ultraviolet rays before coated. Concentrations of anti-c2M3RP, anti-SSA, and anti-SSB were measured in the sera of 240 individuals: 91 patients with primary SS and 149 controls (16 secondary SS, 27 systemic lupus erythematosus, 40 rheumatoid arthritis and 66 healthy controls). Diagnostic properties of anti-c2M3RP were determined by receiver-operating characteristic curve analysis.</p><p><b>RESULTS</b>The prevalence of serum IgA anti-c2M3RP antibodies in patients with pSS (46%, 42/91) was significantly higher than that in patients with systemic lupus erythematosus (19%, 5/27), in rheumatoid arthritis (15%, 6/40) and in healthy controls (5%, 3/66). However, there was no significant difference between the two SS groups (P = 0.727). The diagnostic performance of IgA anti-M3RP antibodies was similar to anti-SSA assay, but had 22% higher sensitivity than anti-SSB. By analyzing of IgA anti-c2M3RP antibodies, combination of anti-SSA and anti-SSB resulted in increased sensitivity, whereas their specificity was not significantly changed.</p><p><b>CONCLUSIONS</b>The improved anti-c2M3RP ELISA is a novel, sensitive, and specific serological test for the diagnosis of SS. The combined application of anti-c2M3RP, anti-SSA and anti-SSB tests can improve the laboratory diagnosis of SS. The IgA anti-c2M3RP antibodies may serve as a novel diagnostic marker for SS.</p>

Rs548234 polymorphism at PRDM1-ATG5 region susceptible to rheumatoid arthritis in Caucasians is not associated with rheumatoid arthritis in Chinese Han population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A previous study has shown that rs548234 polymorphism at PRDM1-ATG5 region is associated with rheumatoid arthritis (RA) in Caucasian populations. The aim of this study was to investigate the effect of rs548234 polymorphism at PRDM1-ATG5 region on susceptibility to RA in Chinese Han population.</p><p><b>METHODS</b>We genotyped 848 RA patients and 1431 matched healthy controls for rs548234 single-nucleotide polymorphism (SNP) with a predesigned TaqMan SNP genotyping assay. Association analyses were performed on the whole data set and on rheumatoid factors (RF) and anti-cyclic citrullinated peptides (anti-CCP) antibody. Finally, we carried out combined analysis of rs548234 association with RA based on the published data.</p><p><b>RESULTS</b>No significant difference in the genotype distribution between RA patients and healthy controls for rs548234 (C/T) polymorphism was found in Chinese Han population, neither in whole data set nor in stratified subsets, e.g. RF and anti-CCP status. Association analysis in different ethnic groups showed that rs548234 at PRDM1-ATG5 region was associated with RA in Caucasian ancestry but not in East Asian population.</p><p><b>CONCLUSIONS</b>Our results showed no involvement of rs548234 at PRDM1-ATG5 region in the susceptibility or clinical relevance of RA in Chinese Han population.</p>

Variation in STAT4 is associated with systemic lupus erythematosus in Chinese Northern Han population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recent studies have identified signal transducer and activator of transcription 4 (STAT4) as a susceptibility gene for systemic lupus erythematosus (SLE) in different populations. In order to examine whether the allele distribution of the single nucleotide polymorphism (SNP) in gene STAT4 rs7574865 in patients with SLE is different from those of healthy controls in Chinese Northern Han population, we investigated whether the variants of STAT4 rs7574865 were associated with any specific clinical features of SLE.</p><p><b>METHODS</b>We genotyped SNPs in STAT4 rs7574865 in 252 patients with SLE and 497 healthy controls. All subjects were from the Northern part of Chinese Han population. The genotypes in rs7574865 were determined by polymerase chain reaction (PCR) and consequence direct sequencing of PCR products in the DNA samples.</p><p><b>RESULTS</b>There was a significant difference in distribution of the SNPs in rs7574865 between the SLE patients and healthy controls. Compared with healthy controls, there was a significant correlation between TT genotypes in rs7574865 and the risk of SLE when GG genotype was used as a reference genotype after adjusting for gender and age. The frequency of T allele in the SLE patients was strongly significantly higher than that of healthy controls. Furthermore, there was a significant difference in the distribution of SNP in rs7574865 between male and female SLE patients, when compared with healthy controls. The frequency of T allele in rs7574865 in male patients was significantly higher than that of male healthy controls or female patients. There was no significant correlation between the frequencies of T allele in STAT4 rs7574865 and the clinical features of SLE.</p><p><b>CONCLUSIONS</b>The SNP rs7574865 in STAT4 is strongly associated with risk of SLE in the Chinese Northern Han population. The TT genotype and T allele in STAT4 rs7574869 are susceptibility factors for SLE, especially for male SLE patients.</p>

Circulating Dickkopf-1 and osteoprotegerin in patients with early and longstanding rheumatoid arthritis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Rheumatoid arthritis (RA) is characterized by inflammation of the synovial membrane, leading to invasion of synovial tissue into the adjacent cartilage matrix with degradation of articular cartilage and bone as a consequence. Dickkopf-1 (DKK-1) and osteoprotegerin (OPG) have been demonstrated to be key molecules involved in bone erosion and bone remodeling. The aim of this study was to explore the potential role of DKK-1 and OPG in different stage of RA.</p><p><b>METHODS</b>The protein levels of DKK-1 and OPG were detected by ELISA. The serum samples were collected from 300 patients with RA and 60 healthy controls. Of which, 150 RA patients were defined as early RA (disease duration < or = 1 year), and other 150 RA patients were defined as longlasting RA (disease duration > or = 5 years). At the time of serum sampling, various clinical and laboratory parameters were assessed. The correlations of DKK-1 or OPG and clinical/laboratory parameters were analyzed.</p><p><b>RESULTS</b>The serum level of DKK-1 was elevated in patients with longstanding RA compared with healthy controls, while no significant difference was observed between the two groups in the level of OPG. In contrast, in early RA patients, the circulating OPG was elevated, while there was no significant difference between the two groups in expression of DKK-1. The serum DKK-1 was correlated with Sharp score and DAS28 in longstanding RA patients. In early RA, age was the only parameter that was significantly related to serum OPG.</p><p><b>CONCLUSIONS</b>There was a cross-talk between DKK-1 and OPG, which involved in bone destruction in RA. In different stage of RA, DKK-1 and OPG may play different roles in the pathogenesis of RA.</p>

Research progression of ?-SYN in Cancer / 国外医学(肿瘤学分册)

?-Synuclein (?-SYN ) .previously identified as a breast cancer specific gene, has a wildly tumor expression profile mainly in advanced stage. As a special chaperone,?- SYN stimulates the proliferation and metastasis of tumor cells through interacting with estrogen receptor and (or) BubR1. Meanwhile, it is also detectable in the serum or urine from tumor patients, which indicates that?- SYN could be potential as a tumor marker for diagnosis and prognosis.

Effects of atrial excitable period on the stability of atrial fibrillation in goats / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of atrial excitable period (EP) on the stability of atrial fibrillation (AF) in goats.</p><p><b>METHODS</b>Ten female goats were instrumented with epicardial electrodes patches on the left atrium (LA) free wall. AF was induced and maintained by a home-made stimulator with frequency of 50 Hz at a 1-second duration and a 2-seconds interval. The stimulator was disconnected regularly. AF-induced duration, average AF cycle length (AFCL), and atrial effective refractory period during AF (ERP(AF)) were measured; EP was calculated by AFCL-ERP(AF).</p><p><b>RESULTS</b>Eight goats were studied. Persistent AF (> 24 h) could be induced in all the 8 goats within 6-16 days. When the induced AF lasted for 3-10 min or 24 h, the AFCL was 98.3 ms +/- 11.0 ms and 84.9 ms +/- 5.2 ms (P < 0.05), respectively, ERP(AF) was 90.5 ms +/- 13.2 ms and 63.0 ms +/- 4.8 ms (P < 0.05), respectively, and EP was 7.8 ms +/- 2.4 ms and 21.9 ms +/- 3.5 ms (P < 0.05), respectively.</p><p><b>CONCLUSION</b>The decrease in ERP(AF) is more significant than the shortening in AFCL, resulting in the gradually widening of EP which may contribute to the perpetuation of AF.</p>