Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study.

Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 affected individuals) from five different populations. We discovered HLA risk factors and four non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21 and reinforced IL12B, PTK2B, and chr21q22 as robust susceptibility loci shared across ancestries. Functional analysis proposed plausible underlying disease mechanisms and pinpointed ETS2 as a potential causal gene for chr21q22 association. We also identified >60 candidate loci with suggestive association (p < 5 × 10-5) and devised a genetic risk score for Takayasu arteritis. Takayasu arteritis was compared to hundreds of other traits, revealing the closest genetic relatedness to inflammatory bowel disease. Epigenetic patterns within risk loci suggest roles for monocytes and B cells in Takayasu arteritis. This work enhances understanding of the genetic basis and pathophysiology of Takayasu arteritis and provides clues for potential new therapeutic targets.

Clinical trait-specific genetic analysis in Behçet's disease identifies novel loci associated with ocular and neurological involvement.

Behçet's disease is a complex inflammatory vasculitis with a broad spectrum of clinical manifestations. The purpose of this study was to investigate the genetics underlying specific clinical features of Behçet's disease. A total of 436 patients with Behçet's disease from Turkey were studied. Genotyping was performed using the Infinium ImmunoArray-24 BeadChip. After imputation and quality control measures, logistic regressions adjusting for sex and the first five principal components were performed for each clinical trait using a case-case genetic analysis approach. A weighted genetic risk score was calculated for each clinical feature. Genetic association analyses of previously identified susceptibility loci in Behçet's disease revealed a genetic association between ocular lesions and HLA-B/MICA (rs116799036: OR = 1.85 [95% CI = 1.35-2.52], p-value = 1.1 × 10-4). The genetic risk score was significantly higher in Behçet's disease patients with ocular lesions compared to those without ocular involvement, which is explained by the genetic variation in the HLA region. New genetic loci predisposing to specific clinical features in Behçet's disease were suggested when genome-wide variants were evaluated. The most significant associations were observed in ocular involvement with SLCO4A1 (rs6062789: OR = 0.41 [95% CI = 0.30-0.58], p-value = 1.92 × 10-7), and neurological involvement with DDX60L (rs62334264: OR = 4.12 [95% CI 2.34 to 7.24], p-value = 8.85 × 10-7). Our results emphasize the role of genetic factors in predisposing to specific clinical manifestations in Behçet's disease, and might shed additional light into disease heterogeneity, pathogenesis, and variability of Behçet's disease presentation across populations.

Sex-specific analysis in Behçet's disease reveals higher genetic risk in male patients.

OBJECTIVES: Behçet's disease tends to be more severe in men than women. This study was undertaken to investigate sex-specific genetic effects in Behçet's disease. METHODS: A total of 1762 male and 1216 female patients with Behçet's disease from six diverse populations were studied, with the majority of patients of Turkish origin. Genotyping was performed using an Infinium ImmunoArray-24 BeadChip, or extracted from available genotyping data. Following imputation and extensive quality control measures, genome-wide association analysis was performed comparing male to female patients in the Turkish cohort, followed by a meta-analysis of significant results in all six populations. In addition, a weighted genetic risk score for Behçet's disease was calculated and compared between male and female patients. RESULTS: Genetic association analysis comparing male to female patients with Behçet's disease from Turkey revealed an association with male sex in HLA-B/MICA within the HLA region with a GWAS level of significance (rs2848712, OR = 1.46, P = 1.22 × 10-8). Meta-analysis of the effect in rs2848712 across six populations confirmed these results. Genetic risk score for Behçet's disease was significantly higher in male compared to female patients from Turkey. Higher genetic risk for Behçet's disease was observed in male patients in HLA-B/MICA (rs116799036, OR = 1.45, P = 1.95 × 10-8), HLA-C (rs12525170, OR = 1.46, P = 5.66 × 10-7), and KLRC4 (rs2617170, OR = 1.20, P = 0.019). In contrast, IFNGR1 (rs4896243, OR = 0.86, P = 0.011) was shown to confer higher genetic risk in female patients. CONCLUSIONS: Male patients with Behçet's disease are characterized by higher genetic risk compared to female patients. This genetic difference, primarily derived from our Turkish cohort, is largely explained by risk within the HLA region. These data suggest that genetic factors might contribute to differences in disease presentation between men and women with Behçet's disease.

Intestinal Behçet Disease: Evaluation With MR Enterography-A Case-Control Study.

OBJECTIVE: The purposes of this study were to discern imaging findings that distinguish Behçet disease from small-bowel Crohn disease, to find initial performance estimates for these findings, and to evaluate the diagnostic value of MR enterography (MRE) for detecting intestinal Behçet disease. MATERIALS AND METHODS: The MRE examinations of 30 consecutively registered patients with established intestinal Behçet disease were reviewed by two blinded readers. The frequencies of MRE findings were compared with those obtained for 30 control subjects with small-bowel Crohn disease who were matched for sex and age. The performance estimates were generated with ileocolonoscopic and histopathologic findings as the reference standard. RESULTS: Polypoid pattern and homogeneous mural enhancement were the findings seen more frequently in Behçet disease (p = 0.000) than in Crohn disease (p = 0.003). Stricture formation, long-segment disease, and involvement of more proximal ileal segments favored small-bowel Crohn disease. The ROC AUCs for polypoid pattern and homogeneous mural enhancement in the detection of intestinal Behçet disease were 0.806 and 0.779. The accuracy of MRE was 70.00% (95% CI, 50.60-85.27%); sensitivity, 57.14% (95% CI, 34.02-78.18%), and specificity, 100% (95% CI, 66.37-100%). CONCLUSION: MRE has potential for use as a radiation-free alternative for clarifying the cause of nonspecific gastrointestinal symptoms in patients with known Behçet disease. However, additional studies are needed to determine the actual value of MRE in patients with Behçet disease and to validate the clinical usefulness of the technique in the detection of unknown intestinal Behçet disease.

Anti-angiotensin II type 1 receptor autoantibodies (AT1R-AAs) in patients with systemic sclerosis: lack of association with disease manifestations.

Angiotensin II type 1 receptor autoantibodies (AT1R-AAs) are known to be associated with malignant hypertension, preeclampsia, and vascular rejection in kidney transplantation. They were also suspected to have pathogenetic role in vasculopathic changes in systemic sclerosis (SSc). Clinical data regarding AT1R-AAs in SSc are scarce. In this work, we will examine the relationship between serum levels of AT1R-AAs and disease manifestations. Serum samples from SSc patients and healthy controls were analyzed for AT1R-AAs by using a commercial ELISA kit. We examined the association of serum levels of AT1R-AA with disease duration, systolic pulmonary artery pressure (sPAP) measurements, and disease manifestations like cutaneous, lung and esophageal involvements, and the presence of digital ulcers in a cross-sectional manner. There was no statistically significant difference in levels of AT1R-AAs between SSc (n = 93) patients and healthy controls (n = 66) (p = 0.23). Serum levels of AT1R-AAs were not correlated with disease duration, sPAP measurements, and showed no association with disease manifestations like lung involvement, esophageal involvement, digital ulcers, and cutaneous fibrosis. In our SSc cohort, AT1R-AA serum levels were not different from healthy subjects and higher levels were not associated with any disease manifestation neither.

Criteria sets for primary Sjogren's syndrome are not adequate for those presenting with extraglandular organ involvements as their dominant clinical features.

Patients with primary Sjogren's syndrome (pSS) may go undiagnosed or be misclassified due to the insidious nature and wide spectrum of the disease. The available several classification criteria emphasize glandular findings. We aimed to analyze the efficiency of various classification criteria sets in patients diagnosed on the clinical basis by expert opinion and to compare those pSS patients who fulfilled these criteria with those who did not. This is a multicenter study in which 834 patients from 22 university-based rheumatology clinics are included. Diagnosis of pSS was made on the clinical basis by the expert opinion. In this study, we only interviewed patients once and collected available data from the medical records. The European criteria, American-European Consensus Group (AECG) and American College of Rheumatology (ACR) Sjogren's criteria were applied. Majority of the patients were women (F/M was 20/1). The median duration from the first pSS-related symptom to diagnosis was significantly shorter in men (2.5 ± 2.3 vs 4.3 ± 5.9 years) (p = 0 < 0.016). When the European, AECG and ACR Sjogren's criteria were applied, 666 patients (79.9%) satisfied at least one of them. In total, 539 patients (64.4%) satisfied the European, 439 (52.6%) satisfied the AECG, and 359 (43%) satisfied the ACR criteria. Among the entire group, 250 patients (29.9%) satisfied all and 168 (20.1%) met none of the criteria. The rates of extraglandular organ involvements were not different between patients who met at least one of the criteria sets and those who met none. There is an urgent need for the modification of the pSS criteria sets to prevent exclusion of patients with extraglandular involvements as the dominant clinical features.

Identification of multiple genetic susceptibility loci in Takayasu arteritis.

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)).

TIR-domain-containing adaptor protein gene TIRAP S180L polymorphism is not increased in Behçet's disease patients in two ethnic cohorts.

OBJECTIVES: The single nucleotide polymorphism (SNP) of TIRAP (Serine 180 leucine, S180L) that is shown to be associated with Behçet's disease (BD) in a European-derived cohort, but not in Middle Eastern patients is investigated in two other populations. METHODS: Two cohorts of BD patients and controls from Turkey (n=797) and Italy (n=633) were genotyped by sequence specific primer-polymerase chain reaction (SSP-PCR) or TaqMan q-PCR assays. RESULTS: Genotype and allele frequencies in TIRAP S180L (rs8177374) were not different between BD patients and controls in either ethnicity. Furthermore, a meta-analysis between the Turkish and the Italian BD cohorts did not reveal an association between this non-synonymous SNP in TIRAP and BD (meta-analysis OR=0.94, meta-analysis p=0.61, Q statistic heterogeneity p=0.11). CONCLUSIONS: TIRAP S180L gene polymorphism, which was previously shown to be associated with BD in a Caucasian population, has been replicated in either Turkish or Italian population in our study.

An aggressive and lethal course of Churg-Strauss syndrome with alveolar hemorrhage, intestinal perforation, cardiac failure and peripheral neuropathy.

Churg-Strauss syndrome (CSS) is a rare type of necrotizing vasculitis affecting small to medium-sized vessels typically characterized by asthma, lung infiltrates, necrotizing granulomas and hypereosinophilia. Herein, we describe a case of CSS presenting severe and aggressive course. A 35-year-old male patient with weight loss, dyspepsia, dyspnea and hemoptysis was admitted. The laboratory analyses indicated a remarkable eosinophilia, elevated levels of serum total IgE and positive cANCA. Thorax CT findings were suggestive of alveolar hemorrhage. Bronchoalveolar lavage revealed alveolar hemorrhage with eosinophilia and transbronchial lung biopsy showed eosinophilic vasculitis. Cardiac enzymes were increased and murmurs were audible revealing cardiomyopathy proven by echocardiography. Pulse cyclophosphamide and methyl prednisolone was immediately started. On the 21st day, intestinal perforation developed and urgent surgery was performed. During a follow-up, although a radiological improvement was observed in the chest X-ray, cardiac failure, peripheral neuropathy and skin lesions developed and high-dose intravenous immunoglobulin and anti-TNF therapy (adalimumab) were applied. Despite the therapy, he died from heart failure and septicemia at 68th day of therapy.

No association of PTPN22 R620W gene polymorphism with rheumatic heart disease and systemic lupus erythematosus.

Rheumatic heart disease (RHD) or acute rheumatic fever (ARF) develops as a consequence of an exaggerated immune response to Group A beta haemolytic streptococci causing pharyngitis. The molecular mimicry appears between human cardiac myosin and M protein of group A streptococcal membranes. The polymorphism of the protein tyrosine phosphatase nonreceptor 22 (PTPN22) gene, which encodes an important negative regulator of T cell activation, has been reported to be associated with susceptibility to several autoimmune diseases such as SLE and RA. The objective of this study was to investigate whether PTPN22 R620W polymorphism confers susceptibility to RHD in Turkish population. PTPN 22 R620W (rs2476601, A/G) polymorphism was genotyped by PCR-RFLP in 121 patients with RHD who fulfilling the revised classification criteria of Jones, and 160 healthy control (HC), and also 137 SLE as a diseased-control. The frequency of GG and AG genotypes were found to be 94% (114), 6% (7) in RHD, respectively and 96% (153) and 4% (7) in HC, respectively. The homozygous AA genotype was not present in RHD and HC. There was no statistically significant difference between RHD and HC according to the frequency of AG heterozygote genotype (P = 0.831; OR = 1.13; 95% CI 0.37-3.46). The frequency of the rare allele A was also very similar in RHD patients and HC (3, 2% respectively). A similar result was also found between SLE and HC. Our results demonstrated that the PTPN22 R620W polymorphism is not associated with RHD nor with SLE in Turkish population.

Genetic Association of a Gain-of-Function IFNGR1 Polymorphism and the Intergenic Region LNCAROD/DKK1 With Behçet's Disease.

OBJECTIVE: Behçet's disease is a complex systemic inflammatory vasculitis of incompletely understood etiology. This study was undertaken to investigate genetic associations with Behçet's disease in a diverse multiethnic population. METHODS: A total of 9,444 patients and controls from 7 different populations were included in this study. Genotyping was performed using an Infinium ImmunoArray-24 v.1.0 or v.2.0 BeadChip. Analysis of expression data from stimulated monocytes, and epigenetic and chromatin interaction analyses were performed. RESULTS: We identified 2 novel genetic susceptibility loci for Behçet's disease, including a risk locus in IFNGR1 (rs4896243) (odds ratio [OR] 1.25; P = 2.42 × 10-9 ) and within the intergenic region LNCAROD/DKK1 (rs1660760) (OR 0.78; P = 2.75 × 10-8 ). The risk variants in IFNGR1 significantly increased IFNGR1 messenger RNA expression in lipopolysaccharide-stimulated monocytes. In addition, our results replicated the association (P < 5 × 10-8 ) of 6 previously identified susceptibility loci in Behçet's disease: IL10, IL23R, IL12A-AS1, CCR3, ADO, and LACC1, reinforcing the notion that these loci are strong genetic factors in Behçet's disease shared across ancestries. We also identified >30 genetic susceptibility loci with a suggestive level of association (P < 5 × 10-5 ), which will require replication. Finally, functional annotation of genetic susceptibility loci in Behçet's disease revealed their possible regulatory roles and suggested potential causal genes and molecular mechanisms that could be further investigated. CONCLUSION: We performed the largest genetic association study in Behçet's disease to date. Our findings reveal novel putative functional variants associated with the disease and replicate and extend the genetic associations in other loci across multiple ancestries.

Evaluation of the functional parameters in scleroderma cases with pulmonary involvement.

To evaluate the relationship between functional changes in the scleroderma patients with pulmonary involvement and the diagnostic tests and to identify the tests that may be helpful in early diagnosis. In this prospective study, 33 scleroderma patients with pulmonary involvement were included. Pulmonary function tests, echocardiography, arterial blood gases, six minute walk tests, thorax high resolution computed tomography were performed and all patients were classified according to MRC dyspnea scores and NYHA(WHO) functional classification. Patients were also asked to conclude Saints Georges Respiratory Questionnaire (SGRQ). DLCO% found to be the earliest deteriorated parameter in our patients. Sensitivity of FVC%/DLCO% ratio, for detecting pulmonary arterial hypertension as a noninvasive method, was found low. SGRQ was found to be correlated with all functional parameters used in scleroderma follow up. Patients with scleroderma should be evaluated for pulmonary involvement and must be followed up ever if they were asymptomatic. Pulmonary function tests, echocardiography, thorax high resolution computed tomography, six minute walk tests are valuable tools that should be used in diagnosis and follow up. NYHA (WHO) functional classification, MRC and Borg dyspnea scores are also helpful for early diagnosis. SGRQ can also be helpful to evaluate the patients functional capacity in diagnosis and follow up as a non invasive parameter.

Empiric antibiotic therapy in acute uncomplicated urinary tract infections and fluoroquinolone resistance: a prospective observational study.

BACKGROUND: The aims of this study were to determine the antimicrobial susceptibility patterns of urinary isolates from community acquired acute uncomplicated urinary tract infections (uUTI) and to evaluate which antibiotics were empirically prescribed in the outpatient management of uUTI. METHODS: Among the patients which were admitted to outpatient clinics of Ankara University Medical Faculty, Ibni-Sina Hospital during 2005-2006, a total of 429 women between the age of 18 and 65 years old who were clinically diagnosed with uUTI and to whom prescribed empirical antibiotics were enrolled in this prospective observational study. Patients' demographical data, urine culture results, resistance rates to antimicrobial agents and prescribed empiric antimicrobial therapy were analyzed. RESULTS: Totally 390 (90.9%) patients among all study population were requested for urine culture by their physicians. 150 (38.5%) of these urine cultures were positive. The most common isolated uropathogen was Escherichia coli (E. coli) (71.3%). The variations of uropathogens according to age and menopause status were not significantly different.The resistance rates of E. coli isolates for ampicillin, ampicillin-sulbactam, amoxicillin-clavulonate, cefuroxime, ceftriaxone, fluoroquinolones (FQ), co-trimoxazole (TMP-SMX) and gentamicin were 55.1%, 32.7%, 32.7%, 23.4%, 15.9%, 25.2%, 41.1%, 6.1% respectively. FQ were the most common prescribed antibiotics (77.9%) (P < 0.001), followed by TMP-SMX (10.7%), fosfomycin (9.2%), nitrofurantoin (2.1%). Treatment durations were statistically longer than the recommended 3-day course (P < 0.001). CONCLUSION: Empirical use of FQ in uUTI should be discouraged because of increased antimicrobial resistance rates.

An analysis of the relationship between autoantibodies and clinical findings in patients with systemic sclerosis

Background/aim: We aimed to investigate the prevalence of anti-RNA polymerase (RNAP) III and other autoantibodies in a group of Turkish patients with systemic sclerosis (SSc) and their relation with clinical features. Materials and methods: The prevalence of anti-RNAP III and other autoantibodies was analyzed in 93 patients with SSc and control groups including 86 patients with systemic lupus erythematosus (SLE) and 65 healthy subjects, respectively. Their relationship with diseases findings was assessed in a cross-sectional manner. Results: Prevalences of anti-RNAP III were 2/93 (2.2%) in SSc, 1/86 (1.2%) in SLE, and 1/65 (1.5%) in the healthy group and there was no difference among groups (P > 0.999). Anti-Sm was significantly more common in SLE patients (P < 0.001), whereas antitopoisomerase I and anticentromere protein B were significantly more common in SSc patients (P < 0.001). There was a significant association between antitopoisomerase I positivity and interstitial lung disease (P < 0.001), and interestingly there was also a significant association between anti-SS-A 52 positivity and the presence of digital ulcers in patients with SSc. Conclusion: Our data show that anti-RNAP III in SSc patients was low in frequency in a Turkish population.

Antinucleosome antibodies and systemic lupus erythematosus.

The aim of this study is to investigate the prevalence of antinucleosome antibody in systemic lupus erythematosus (SLE) and their association with disease activity and renal involvement. The study included 131 patients with SLE, 74 rheumatoid arthritis, 26 systemic sclerosis, and 50 healthy individuals. Antinucleosome antibody and anti-dsDNA antibody were measured by an enzyme-linked immunosorbent assay (ELISA). Antinuclear antibody was tested by immunofluorescence using HEp-2 cells. Out of 131 SLE patients, 72 (54.9%) were seropositive for antinucleosome antibody, which was significantly higher than only 3 of 74 (4%) patients with rheumatoid arthritis (chi(2) = 52.82, P < 0.001); none of the patients with systemic sclerosis and 50 healthy individuals were seropositive. The sensitivity and specificity of antinucleosome antibodies in SLE were 83.6% and 70%, respectively. Fifty-one (38.9%) of SLE patients had renal involvement. Among these patients, the rate of antinucleosome positivity and anti-dsDNA were 74.5% and 78.4%, respectively. Antinucleosome antibodies were found to be 31.4% positive in SLE patients lacking anti-dsDNA antibody. Antinucleosome antibodies significantly correlated with disease activity (r = 0.428, P < 0.001) and anti-dsDNA (r = 0518, P < 0.001). The positivity of antinucleosome antibodies was significantly higher in patients with renal disease than the subjects without renal disease (chi(2) = 12.89, P < 0.001). The results of our study have revealed that in SLE patients, antinucleosome antibody could be a useful parameter for the assessment of disease activity or renal involvement.

Antibodies to beta2-glycoprotein-I: relation of anticardiolipin antibodies with clinical and laboratory parameters in patients with systemic lupus erythematosus.

OBJECTIVES: There are controversial reports on the frequency of antiphospholipid antibodies (aPL) in patients with systemic lupus erythematosus (SLE). Thus, we aimed to determine the frequency and clinical importance of aPL isotypes in Turkish patients with SLE. DESIGN AND METHODS: Fifty-nine patients with SLE and 41 healthy controls were included. Serum aPL levels were measured both in patients and healthy subjects by ELISA. RESULTS: Fifteen of the patients with SLE had the antiphospholipid syndrome (APS) (25.4%). The percentage of anticardiolipin antibody (aCL)-positive SLE patients among all patients was 56%. At least one isotype of anti-beta(2)-glycoprotein I (beta(2)-GPI) antibody was positive in 83% of patients. The positivity rates of aCL and anti-beta(2)-GPI antibodies in patients with or without APS were higher than the healthy controls. There were positive correlations between isotypes of IgM aCL, IgG and IgM anti-beta(2)-GPI and manifestations of APS. CONCLUSION: It seems that the isotypes of IgM aCL, IgG and IgM anti-beta(2)-GPI are correlated with manifestations of APS. They may play a role in pathogenesis and may be helpful in establishing the diagnosis.

Clinical manifestations and antiphosphatidylserine antibodies in patients with systemic lupus erythematosus: is there an association?

OBJECTIVE: Antiphospholipid antibodies are a group of heterogeneous autoantibodies which have been reported in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) in association with thrombosis, fetal loss, and thrombocytopenia. In this study, we aimed to reveal the prevalence and correlation of IgG, IgA, and IgM isotypes of antibodies to cardiolipin (aCL) and antiphosphatidylserine (aPS) with clinical and laboratory manifestations of SLE patients. METHODS: Fifty-nine SLE patients and 41 healthy controls were included. Fifteen of patients (25.4%) had secondary APS. aCL and aPS antibody assays were performed by enzyme-linked immunosorbent assay. RESULTS: All isotypes of aCL and aPS antibodies except IgG were higher in patients with or without APS than those in the healthy controls (p<0.001). The most significant associations were found among migraine and IgA aCL (p<0.001), livedo reticularis and both IgM aCL and IgM aPS (p<0.001), migraine and IgM aCL (p<0.01), pulmonary involvement and IgM aCL (p<0.01), migraine and IgA aPS (p<0.01), and both thrombosis and migraine with IgM aPS (p<0.01). CONCLUSION: A relatively high prevalence of aCL and aPS antibodies was found in our SLE patients. It seems that isotypes of IgM aCL, IgM aPS, IgA aCL, and IgA aPS antibodies are correlated well with migraine and IgM aPS with thrombosis in SLE patients with secondary APS. The assessment of both IgM and IgA isotypes of aPS and aCL antibodies may be helpful in predicting these manifestations.

The lack of genetic association of the Toll-like receptor 2 (TLR2) Arg753Gln and Arg677Trp polymorphisms with rheumatic heart disease.

UNLABELLED: Acute rheumatic fever (ARF) is a non-suppurative inflammatory disease after group A, beta haemolytic streptococcal pharyngitis. Certain individuals can develop ARF. This finding implies variability in host predisposition to ARF. A variety of studies have linked specific genetic markers with ARF or rheumatic heart disease (RHD) as a sequelae of ARF. For this purpose, we aimed to search the role of polymorphisms in Toll-like receptor-2 and -4 (TLR2 and TLR4) gene in Turkish patients with RHD. This study included a total 84 patients with RHD, ages ranging between 18 and 65, 25 male and 59 female, fulfilling the revised classification criteria of Jones. One hundred forty healthy unrelated persons were selected as a control group. Genotype analysis: DNA was extracted from whole blood. TLR4 gene (Asp 299Gly and Thr399Ile) and TLR2 gene (Arg753Gln and Arg677Trp) polymorphisms were genotyped by the previously reported method. STATISTICAL ANALYSIS: binary logistic regression models were used. Results were expressed as odds ratios (OR) with corresponding 95% confidence intervals (95% CI). Significant level was predefined at 0.05. There was a significant difference for carrying Ile allele in the 399 position in the patients compared to healthy controls (OR = 5.26, 95% CI, 1.40-19.73, p = 0.014). In the TLR4 gene, Asp 299Gly polymorphism did not reach to a statistically significant value (OR = 3.02). We found no Arg753Gln polymorphism of the TLR2 gene in the patient group. There were three heterozygote samples in the healthy group. We did not detect Arg677Trp polymorphism of the TLR2 gene in both patient and control groups.

Low serum fibroblast growth factor 2 levels not accompanied by increased serum pentraxin 3 levels in patients with systemic sclerosis.

There are scarce clinical data regarding serum pentraxin 3 (PTX3) and fibroblast growth factor 2 (FGF2) in patients with systemic sclerosis (SSc). Study was conducted to evaluate serum levels in our SSc cohort. Serum PTX3 and FGF2 concentrations were compared among SSc, disease control (systemic lupus erythematosus (SLE)), and healthy control groups. We also examined the association of serum levels of PTX3 and FGF2 with disease manifestations. Serum PTX3 levels were similarly distributed among SSc (n = 93) and healthy groups (n = 66) (p = 1.00) while PTX3 levels were higher in SLE controls (n = 86) compared to both SSc and healthy groups. PTX3 levels were higher in limited SSc cases compared to diffuse cases (p = 0.016). Median PTX3 levels in SSc cases with lung involvement were lower compared to cases with no lung involvement (p = 0.006). Patients with SSc had significantly lower serum levels of FGF2 compared to SLE and healthy groups. Serum FGF2 concentration was undetectable in 61.3% of cases with SSc while 30.2% of SLE and only 4.5% of healthy cases had undetectable FGF2 levels (p < 0.01). Diffuse and limited SSc cases, as well as cases with and without lung involvement, had similar rates of undetectable serum FGF2 levels (p = 0.15 and p = 0.59, respectively). FGF2 levels were mostly undetectably low in patients with SSc, and serum PTX3 was lower in diffuse SSc and in cases with lung involvement compared to limited SSc and cases with no lung involvement, respectively, in our cohort.