A retrospective record review of tuberculous infections in rheumatoid arthritis patients on biologics in Malaysia.

INTRODUCTION: The aim of this study was to analyse the clinical characteristics of patients with rheumatoid arthritis receiving biologics therapy and investigate the association between types of biologics and tuberculosis (TB) infections in 13 tertiary hospitals in Malaysia. MATERIALS AND METHODS: This was a retrospective study that included all RA patients receiving biologics therapy in 13 tertiary hospitals in Malaysia from January 2008 to December 2018. RESULTS: We had 735 RA patients who received biologics therapy. Twenty-one of the 735 patients were diagnosed with TB infection after treatment with biologics. The calculated prevalence of TB infection in RA patients treated with biologics was 2.9% (29 per 1000 patients). Four groups of biologics were used in our patient cohort: monoclonal TNF inhibitors, etanercept, tocilizumab, and rituximab, with monoclonal TNF inhibitors being the most commonly used biologic. The median duration of biologics therapy before the diagnosis of TB was 8 months. 75% of patients had at least one co-morbidity and all patients had at least one ongoing cDMARD therapy at the time of TB diagnosis. More than half of the patients were on steroid therapy with an average prednisolone dose of 5 mg daily. CONCLUSION: Although the study population and data were limited, this study illustrates the spectrum of TB infections in RA patients receiving biologics and potential risk factors associated with biologics therapy in Malaysia.

[Development and clinical application of the health education knowledge assessment questionnaire for gout].

OBJECTIVE: To develop and test the health education knowledge assessment questionnaire for gout and to investigate the understanding degree of health education knowledge in patients with gout. METHODS: From June 2019 to June 2019, 150 cases of gout patients were enrolled.According to the literature review and the healthy education requirements of gout patients, the framework of education knowledge system was preliminarily formed.The pre-test questionnaire was obtained through two rounds of he Delphi technique.A survey of 150 patients with gout was carried out.The analysis and selection of the questionnaire were based on the coefficient of variation, the analysis of determination value, the correlation coefficient of the items and the total scores, and the exploratory factor analysis.In this study, we evaluated the reliability of internal consistency, semi-reliability.Validity test mainly included content validity and construct validity.In addition, a total of 150 patients with gout in our hospital and outpatient gout were selected to investigate the understanding degree of health education knowledge from June 2019 to December 2019. RESULTS: The significance of the first level index of the questionnaire was 3.83-5.00, the secondary index was 3.00-4.83, and the variation coefficient of each item was 0.31-1.23, and the critical ratio(CR) value of each item in this questionnaire was 3.168-8.333.The Pearson correlation coefficient of each item and the total score of this study was 0.319-0.544.After exploratory factor analysis, some topics were deleted in four dimensions, and there were 16 entries in the final questionnaire.Cronbach' s α coefficient of this questionnaire was 0.715, split-half reliability Spearman-Brown coefficient was 0.785, and retest reliability coefficient was 0.729. The correlation coefficient between each factor of this questionnaire and the total questionnaire was 0.300-0.701, and the correlation coefficient between each item of the questionnaire and each factor was 0.402-0.732, all P < 0.05. The results were statistically significant. By questionnaire investigation, the total score of questionnaire was (6.85±3.22), the score of disease-related knowledge was (2.03±1.24), the score of dietary guidance was (1.53± 1.06), the score of exercise guidance was (2.19±1.24), the score of medication guide was (1.24±1.22). CONCLUSION: The Health Education Knowledge Assessment Questionnaire For Gout has a good reliability and validity for measuring related content, the compilation process is scientific and the content is comprehensive, which can be further applied in clinic.The understanding degree of health education knowledge is low in Chinese patients with gout, and knowledge of gout medicine is lacking especially.

The Future of Neurocritical Care Research: Proceedings and Recommendations from the Fifth Neurocritical Care Research Network Conference.

The Fifth Neurocritical Care Research Network (NCRN) Conference held in Boca Raton, Florida, in September of 2018 was devoted to challenging the current status quo and examining the role of the Neurocritical Care Society (NCS) in driving the science and research of neurocritical care. The aim of this in-person meeting was to set the agenda for the NCS's Neurocritical Care Research Central, which is the overall research arm of the society. Prior to the meeting, all 103 participants received educational content (book and seminar) on the 'Blue Ocean Strategy®,' a concept from the business world which aims to identify undiscovered and uncontested market space, and to brainstorm innovative ideas and methods with which to address current challenges in neurocritical care research. Three five-member working groups met at least four times by teleconference prior to the in-person meeting to prepare answers to a set of questions using the Blue Ocean Strategy concept as a platform. At the Fifth NCRN Conference, these groups presented to a five-member jury and all attendees for open discussion. The jury then developed a set of recommendations for NCS to consider in order to move neurocritical care research forward. We have summarized the topics discussed at the conference and put forward recommendations for the future direction of the NCRN and neurocritical care research in general.

Treat-to-target (T2T) of serum urate (SUA) in gout: a clinical audit in real-world gout patients.

Treat-to-target (T2T) for gout has been established recently to improve its management, which has been reported to be sub-optimal with significant gaps between the goals of treatment and day-to-day clinical practice. T2T recommended a goal of serum urate (SUA) target of <360 µmoI/L in all patients with gout and <300 µmoI/L in patients with tophaceous or severe gout. T2T strategy was applied in the management of gout patients in two Rheumatology clinics from 1 January 2016 onwards. We performed a clinical audit to assess T2T of SUA in gout patients and to identify causes for failure to achieve target SUA among them. There were a total of 304 patients for our analysis. They were of multi-ethnic origin with male predominance (88.8%). They had a mean age of 57.7+13.7 years and mean disease duration of 10.1+8.7 years. The most common comorbidities were hypertension (76.2%), dyslipidemia (52.5%) and diabetes mellitus (DM) (27.4%). Our patients' body mass indexes showed that 47.7% were obese while 34.2% were overweight. Up to 62.4% of our patients had tophi and 42.6% had joint deformities. Only 34.9% of patients achieved target SUA. Nonadherence (52.3%) was the main reason identified for failure to achieve target SUA. The independent predictors for failure to achieve target SUA were nonadherence (HR=7.84, p=0.000) and presence of tophi (HR=1.95, p=0.001).

Systemic lupus erythematosus pregnancies: ten-year data from a single centre in Malaysia.

We performed a retrospective study of all systemic lupus erythematosus (SLE) pregnancies during a 10-year period (2006-2015) to describe the clinical features, maternal and foetal outcomes in our centre. There were 115 pregnancies in 86 women with SLE. Our patients had a mean age of 29.1 years (SD 5.80) and a mean disease duration of 44.63 months (SD 41.17). Fifteen patients had antiphospholipid syndrome (APS). Our patients had complicated pregnancies: 26.1% had SLE flares, 13.9% had pre-eclampsia and 45.1% needed caesarean sections. There were 23.3% foetal losses and 25% preterm deliveries in our patients. There was a higher rate of unplanned pregnancies and lupus flare among pregnancies with active SLE at conception. Pregnancies in lupus nephritis have higher incidence of lupus flares during pregnancy but similar maternal and foetal outcomes compared to those without nephritis. The prognostic indicators for adverse foetal outcome in our patients were flare of SLE (HR 4.08 [CI 95% 1.65-10.13, p < 0.01]) and APS (HR 3.07 [CI 95% 1.12-8.42, p < 0.05]) and the prognostic indicator for adverse maternal outcome was hypertension (HR 3.58 [CI 95% 1.30-9.90, p < 0.05]). Lupus pregnancies in our centre remained as high-risk pregnancies with significant maternal and foetal complications.

Safety and efficacy of factor XI (FXI) concentrate use in patients with FXI deficiency: a single-centre experience of 19 years.

AIM: Factor XI (FXI) concentrate is a pooled human plasma-derived factor concentrate used as replacement therapy for patients with FXI deficiency, which provides a predictable response and consistent haemostatic cover in emergency or elective situations. It has previously been implicated in adverse events such as thrombosis and inhibitor formation, with rare case reports of fatal incidents. We sought to establish the incidence of such complications in a retrospective case series between 1994 and 2012 at the Haemophilia Comprehensive Care Centre at Royal Free Hospital, London, UK. METHODS: Patients who received FXI concentrate had their medical records reviewed to extract information and specific adverse events recorded such as failure of treatment with further bleeding, suspected viral transfusion transmitted infection (TTI), thrombosis or inhibitor formation. RESULTS: Eighty-six patients received 242 treatment episodes of FXI concentrate. Ninety percent of treatment episodes were covered with BPL FXI concentrate and 10% with LFB Hemoleven. Twelve (5%) adverse events were recorded, with eight (3.3%) of all treatment episodes were related to persistent bleeding postconcentrate infusion and there were 4 (1.7%) non-bleeding adverse events. No viral TTIs were identified. There were two recorded inhibitors, one thrombotic event (central retinal artery occlusion) and one transfusion reaction. No patient suffering an adverse event resulted in long-term morbidity. CONCLUSION: Our experience of FXI concentrate use demonstrates infrequent minor adverse events related to its administration and is a safe product to use.

Real-world experiences of folic acid supplementation (5 versus 30 mg/week) with methotrexate in rheumatoid arthritis patients: a comparison study.

The objective of this study was to compare the tolerability of methotrexate in two different regimes of folic acid (FA) supplementation in rheumatoid arthritis (RA). We performed a multicenter, cross-sectional observational cohort study on 240 RA patients with 120 patients each in 5 mg of FA weekly and 30 mg of FA weekly supplementation. There were no significant differences for side effects (14.2 versus 22.5%, P=0.523) and discontinuation of methotrexate (3.6 versus 13.3%, P=0.085). RA patients given 5 mg of FA weekly supplementation had a lower disease activity score 28 compared to 30 mg of FA weekly supplementation [3.44 (1.10) versus 3.85 (1.40), P=0.014]. FA supplementation of 5 mg per week and 30 mg per week was associated with similar tolerability of methotrexate in RA patients.

The Sarawak lupus cohort: clinical features and disease patterns of 633 SLE patients in a single tertiary centre from East Malaysia.

Systemic lupus erythematosus (SLE) has been well studied in West Malaysian populations but lacking in East Malaysian populations. The aim of this study was to examine the clinical features and disease patterns of patients with SLE in a multiethnic East Malaysian population in Sarawak. All SLE patients who were treated in Sarawak General Hospital were reviewed in a retrospective longitudinal study using a standard protocol from 1 January 2006 to 31 December 2013. There were a total of 633 patients in our study with the female to male ratio of 12:1. Our study patients were of multiethnic origins with predominant Chinese ethnic group. They had a mean age of 36.9 ± 13.2 years and a mean duration of illness of 7.2 ± 6.0 years. The main involvements were haematological (74.2 %), malar rash (64.0 %) and renal (58.6 %). Chinese patients were less likely to have discoid lupus, pleuritis and pericarditis, while Malay patients were more likely to have arthritis. Bidayuh patients were more likely to have oral ulcer. Secondary antiphospholipid syndrome was more common in Chinese. The majority of patients were in clinical remission with low SDI. There were 58 deaths (9.2 %) during 2006-2013 with the main causes of death being flare of disease and infection.

KPT-330 has antitumour activity against non-small cell lung cancer.

BACKGROUND: We investigated the biologic and pharmacologic activities of a chromosome region maintenance 1 (CRM1) inhibitor against human non-small cell lung cancer (NSCLC) cells both in vitro and in vivo. METHODS: The in vitro and in vivo effects of a novel CRM1 inhibitor (KPT-330) for a large number of anticancer parameters were evaluated using a large panel of 11 NSCLC cell lines containing different key driver mutations. Mice bearing human NSCLC xenografts were treated with KPT-330, and tumour growth was assessed. RESULTS: KPT-330 inhibited proliferation and induced cell cycle arrest and apoptosis-related proteins in 11 NSCLC cells lines. Moreover, the combination of KPT-330 with cisplatin synergistically enhanced the cell kill of the NSCLC cells in vitro. Human NSCLC tumours growing in immunodeficient mice were markedly inhibited by KPT-330. Also, KPT-330 was effective even against NSCLC cells with a transforming mutation of either exon 20 of EGFR, TP53, phosphatase and tensin homologue, RAS or PIK3CA, suggesting the drug might be effective against a variety of lung cancers irrespective of their driver mutation. CONCLUSIONS: Our results support clinical testing of KPT-330 as a novel therapeutic strategy for NSCLC.

Oral health of older people admitted to hospital for needs assessment.

OBJECTIVES: To describe the clinical oral health status, treatment needs and oral-health-related quality of life (OHRQoL) of older people admitted to older persons' wards at Dunedin Public Hospital due to a sudden worsening of their general health. Participants and methods: A systematic oral assessment was undertaken for a consecutive case series of 200 patients (59.5% female; mean age 82.6 years, sd 6.6) admitted to older person's wards at Dunedin Public Hospital. The Oral Health Impact Profile-20 (OHIP-20) was used to assess OHRQoL. RESULTS: One in three (36.0%) had been living independently at home prior to admission, and over half (55.0%) had been admitted for a medical reason which required assessment. Half (50.0%) of the participants were dentate (with an average of 16.8 teeth). There was an average of 1.9 decayed teeth present in the dentate group; 70.7% of individuals required restorations or extractions, and about 90% required only simple scaling of the teeth and prophylaxis. A reline or a replacement denture were required by three-quarters of those with dentures. Almost two-thirds of participants did not have a regular dentist, and fewer than one in three had made a dental visit in the previous year. One in six described their oral health as 'fair' or 'poor', and just under one-third reported dry mouth. Dentate participants, those without xerostomia, and those reporting better oral health had better OHRQoL, reflected in lower OHIP-20 scores. Affecting 37.1% of participants, functional limitation was the most commonly experienced of the OHIP-20 domains, followed by physical disability and physical pain (18.0% and 15.6% respectively). CONCLUSIONS: The oral health of medically compromised and functionally dependent but cognitively competent older people in this study is generally poor. If transfer to long-term care is indicated, early and proper preventive measures and appropriate dental contact should be advocated in order to reduce morbidity and improve quality of life for older people.

Acute Gout in Hospitalized patients in Sarawak General Hospital.

we performed a prospective study of all hospitalized patients with a diagnosis of Gout in Sarawak General hospital from 1st July 2011 to 1st July 2012. There were a total of 126 patients in our study of which 112 (88.9%) were males. The majority of our patients were from the indigenous populations (71.7%). They have a mean age of 60.0 ± 14.2 years. Most of our patients were overweight (68%) with comorbities of hypertension (78.6%), Chronic Kidney Failure (48.4%), Type II diabetes Mellitus (30.2%), dyslipidemia (27.8%) and Ischaemic heart disease (11.9%). Polyarticular gouty arthritis was the main presenting pattern during hospitalization (88.1%). The mean length of stay for our patients was 9.8 ± 6.0 days which was significantly longer than the mean length of stay for other patients without gout (p<0.05). Only 17 patients had gout on admission and the majority developed gout during hospitalizations. Our patients were admitted respectively for medical problems (45.4%), surgical problems (28.6%) and orthopaedic problems (9.2%). Colchicine (73.8%) and steroid (40.5%) were the main stays of treatment for our patients. Our hospitalized gout patients were complicated patients with multiple comorbidities.

Causes and predictors of mortality in hospitalized lupus patient in Sarawak General Hospital, Malaysia.

Systemic lupus erythematosus (SLE) is a serious autoimmune disease that can be life threatening and fatal if left untreated. Causes and prognostic indicators of death in SLE have been well studied in developed countries but lacking in developing countries. We aimed to investigate the causes of mortality in hospitalized patients with SLE and determine the prognostic indicators of mortality during hospitalization in our center. All SLE patients who were admitted to Sarawak General Hospital from January 1, 2006 to December 31, 2010, were followed up in a prospective study using a standard protocol. Demographic data, clinical features, disease activities and damage indices were collected. Logistic regression and Cox regression analysis were used to determine the prognostic indicators of mortality in our patients. There were a total of 251 patients in our study, with the female to male ratio 10 to 1. Our study patients were of multiethnic origins. They had a mean age of 30.5 ± 12.2 years and a mean duration of illness of 36.5 ± 51.6 months. The main involvements were hematologic (73.3%), renal (70.9%) and mucocutaneous (67.3%). There were 26 deaths (10.4%), with the main causes being: infection and flare (50%), infection alone (19%), flare alone (19%) and others (12%). Independent predictors of mortality in our cohort of SLE patients were the presence of both infection and flare of disease (hazard ratio (HR) 5.56) and high damage indices at the time of admission (HR 1.91). Infection and flare were the main causes of death in hospitalized Asian patients with SLE. The presence of infection with flare and high damage indices at the time of admission were independent prognostic indicators of mortality.

A profile of gout patients in Sarawak.

We performed a prospective study of all patients diagnosed with gout and who received treatment in Sarawak General Hospital from 1 July 2010 to 31 December 2010. There was a total of 138 patients in our study of which 92 (66.7%) were from the indigenous populations. They have a mean age of 56.5 ± 12.5 years with a mean duration of illness of 11.6 ± 8.7 years. The mean lag time between symptom onset to the diagnosis of gout was 2.8 ± 4.8 years and a mean lag time to appropriate treatment of gout of 8.8 ± 8.4 years. Sixty-six (47.8%) patients have family history of gout. The common complications of gout in our patients were tophi (47.1%), joint deformities (39.1%), kidney stones (16.7%), and uric acid nephropathy (0.7%). Hospitalization occurred in 93 (67.4%) patients. Gout is a serious medical problem in our centre. Gout affects middle-aged men, especially the indigenous populations. Almost half of our patients have a family history of gout and have tophi formations. Our gout patients have a significant delay in diagnosis and appropriate treatment, thus contributing to more complications and hospitalizations in our centre. There is an urgent need to educate both patients and healthcare workers on gout and its treatment to reduce the burden of chronic gout in Sarawak.

Decreased serum voriconazole levels caused by hepatic enzyme induction after rifapentine discontinuation: a case report and literature review.

BACKGROUND: Rifapentine is a rifamycin with unique bactericidal activity against Mycobacterium tuberculosis. It is also a potent inducer of CYP3A activity. However, the duration of rifapentine-induced hepatic enzyme activity after withdrawal is unclear. CASE REPORT: We report a case of a patient with Aspergillus meningitis treated with voriconazole after discontinuing rifapentine. Within ten days of rifapentine discontinuation, serum levels of voriconazole failed to reach the effective treatment range. CONCLUSIONS: Rifapentine is a potent inducer of hepatic microsomal enzymes. The induction of hepatic enzymes may exceed ten days after rifapentine discontinuation. Clinicians should be reminded of residual enzyme induction by rifapentine, especially when treating critically ill patients.

Efficacy of Danggui Buxue decoction on diabetic nephropathy-induced renal fibrosis in rats and possible mechanism.

OBJECTIVE: To observe the efficacy of Danggui Buxue decoction (, DBD) on diabetic nephropathy-induced renal fibrosis in rats, and to study the possible mechanism. METHODS: Sixty male Goto Kakizaki (GK) rats were randomly assigned to the model group, gliquidone group, astragaloside IV group, and high-, medium- and low-doses DBD groups. After 8 weeks, changes in body weight, blood glucose, serum creatinine, serum urea nitrogen, and total cholesterol were observed. Changes in transforming growth factor-ß1 (TGF-ß1), Smad3, and Smad5 pathways and the expression of the fibrosis-related proteins collagen IV (col IV), α-smooth muscle actin (α-SMA), and vimentin were assessed. The degree of renal fibrosis was observed by immunohistochemistry and Mason staining. The expression of interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor (TNF-α), and C-reactive protein (CRP) in the kidneys was assessed using enzyme linked immunosorbent assay. RESULTS: Our experiments showed that DBD effectively reduced blood glucose, blood urea nitrogen, and creatinine levels after 8 weeks of administration, improved renal function in diabetic rats, alleviated renal fibrosis, and reduced the renal tissue levels of IL-6, IL-10, TNF-α, and CRP. Furthermore, DBD decreased the expression of TGF-ß1, Smad3, col IV, α-SMA, and vimentin in renal tissues and increased the expression of Smad5. CONCLUSIONS: DBD ameliorates diabetic renal interstitial fibrosis by modulating the TGF-ß1/Smads pathway.

Mutations in the SLC2A9 gene cause hyperuricosuria and hyperuricemia in the dog.

Allantoin is the end product of purine catabolism in all mammals except humans, great apes, and one breed of dog, the Dalmatian. Humans and Dalmatian dogs produce uric acid during purine degradation, which leads to elevated levels of uric acid in blood and urine and can result in significant diseases in both species. The defect in Dalmatians results from inefficient transport of uric acid in both the liver and renal proximal tubules. Hyperuricosuria and hyperuricemia (huu) is a simple autosomal recessive trait for which all Dalmatian dogs are homozygous. Therefore, in order to map the locus, an interbreed backcross was used. Linkage mapping localized the huu trait to CFA03, which excluded the obvious urate transporter 1 gene, SLC22A12. Positional cloning placed the locus in a minimal interval of 2.5 Mb with a LOD score of 17.45. A critical interval of 333 kb containing only four genes was homozygous in all Dalmatians. Sequence and expression analyses of the SLC2A9 gene indicated three possible mutations, a missense mutation (G616T;C188F) and two promoter mutations that together appear to reduce the expression levels of one of the isoforms. The missense mutation is associated with hyperuricosuria in the Dalmatian, while the promoter SNPs occur in other unaffected breeds of dog. Verification of the causative nature of these changes was obtained when hyperuricosuric dogs from several other breeds were found to possess the same combination of mutations as found in the Dalmatian. The Dalmatian dog model of hyperuricosuria and hyperuricemia underscores the importance of SLC2A9 for uric acid transport in mammals.

Endothelial nitric oxide synthase and nicotinamide adenosine dinucleotide phosphate oxidase p22phox gene (C242T) polymorphisms and systemic lupus erythematosus in a Chinese Population.

Genetic polymorphisms in the endothelial nitric oxide synthase (eNOS) and nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase p22phox are linked with the expression and/or progression of vascular disease. We hypothesized that these polymorphisms may influence the development and/or progression of systemic lupus erythematosus (SLE), given their linkage with vascular disease. DNA from patients with SLE (n = 90) and their age- and sex-matched controls (n = 86) from The Second Xiangya Hospital of Central South University was assessed for eNOS and NADPH oxidase p22phox polymorphisms. These polymorphisms were examined by restriction fragment length polymorphism-polymerase chain reaction. The allele frequency of the NADPH oxidase p22phox gene C242T polymorphisms significantly varied between the SLE patients and the controls. We found no association of the eNOS polymorphism with the development of renal disease. These results indicated that the etiology of patients with SLE is associated with NADPH oxidase p22phox gene C242T polymorphisms. There was no significant increased risk of SLE associated with eNOS polymorphisms in the Chinese population.

Methylguanidine cytotoxicity on HK-2 cells and protective effect of antioxidants against MG-induced apoptosis in renal proximal tubular cells in vitro.

Methylguanidine (MG), a small molecule among guanidine compounds, is a product of protein catabolism. The concentration of MG in the serum of uremic patients is nearly 80 times of that in the serum of normal people. The present study was designed to explore the toxic effect of MG on renal proximal tubular cells as well as the protective effect of antioxidants PGE1 and probucol against MG-induced apoptosis in renal proximal tubular cells. HK-2 cells were used as the subject. The cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. N-Acetyl-3-D-glucosaminidase (NAG) activity, malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity were determined. Cell apoptosis was determined by flow cytometry (light scatter and propidium iodide/annexin V-FTC fluorescence) and by nuclear staining with Hoechst 33258. Cells were exposed to MG (0.25, 0.5, or 1 mmol/L), MG (0.5 mmol/L) + PGE1 (2 microg/L), and MG (0.5 mmol/L) + probucol (20 micromol/L) respectively for 24 h. MG induced a significant dose-dependent loss of cell viability. Both PGE1 and probucol improved the viability of MG-treated HK-2 cells. Cells showed apoptotic morphology (deepened stain, karyopyknosis, and apoptotic body) when exposed to 0.5 mmol/L MG for 24 h, and the apoptosis ratio was increased compared with the control. The presence of PGE1 or probucol significantly lowered the apoptotic ratio. Moreover, PGE1 or probucol notably decreased the MDA content and increased the SOD activity compared with when the cells were treated with MG only. The results of the present study clearly demonstrate that MG could promote apoptosis of renal proximal tubular cells in vitro. Both PGE1 and probucol could protect renal proximal tubular cells from MG-induced apoptosis.

The relationship between the TGF-beta1 gene -509C/T polymorphism and tubulointerstitial damage resulting from primary nephrotic syndrome.

BACKGROUND: The aim of this study was to investigate the correlation between the transforming growth factor (TGF)-beta1 gene -509C/T polymorphism and the susceptibility to primary nephrotic syndrome (PNS), and in particular to the severe degree of tubulointerstitial damage (TID) seen in Chinese. METHODS: Ninety-eight PNS patients and 128 normal controls were studied. The extent of tubulointerstitial changes was evaluated and patients were divided into two groups according to the severe or mild degree of TID. The TGF-beta1gene -509C/T polymorphism was detected with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, and the serum level of TGF-beta1 was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: No statistical differences in genotype or allele frequency of the TGF-beta1 gene -509C/T were found between PNS and normal subjects. However, T allele and CT + T T genotype frequency were higher in the PNS with severe TID than the mild TID and controls. Additionally, the serum concentration of TGF-beta1 was significantly higher in the PNS with severe TID group than the other two groups and in the T T genotype individuals than the CC and CT genotype individuals. A logistic regression analysis demonstrated that TGF-beta1 gene -509C/T genotype was the risk factor of TID in PNS patients [OR (odd ratio) 2.34, confidence interval (CI) 0.98-3.46, p = 0.012]. CONCLUSION. TGF-beta1 gene -509C/T polymorphism was associated with severe TID. The higher value in serum concentration of TGF-beta1 was also associated with severe TID and the T T genotype/T allele. T allele gene might be the important risk factor for susceptibility.