Genetic susceptibility to SLE is associated with TNF-alpha gene polymorphism -863, but not -308 and -238, in Thai population

The production of cytokine varies among individuals and correlates with the polymorphism of cytokine genes. Three functional single nucleotide polymorphisms (SNPs) at position -863, -308, and -238 in the tumour necrosis factor alpha (TNF-alpha) gene promoter were analysed for association with systemic lupus erythematosus (SLE) (n = 154), and clinical manifestations in a Thai population were compared with 154 ethnically matched controls. The genotyping was determined by polymerase chain reaction-restriction fragment length polymorphism method. The association between these SNPs and SLE was analysed using chi-squared test. The -863A allele and -863A, -308G, -238G haplotype were found to be significantly increased in SLE patients (25%) compared with healthy controls (15.3%) (Pc = 0.009, OR = 1.85, 95% CI = 1.21-2.83). In addition -863A allele was found to be significantly increased in the SLE group with Raynaud's phenomenon compared to SLE without Raynaud's phenomenon (35% vs. 19.4%) (Pc = 0.048, OR = 2.23, 95% CI = 1.21-4.10). The -863A allele of TNF-alpha gene and the extended haplotype of -863A, -308G, -238G can be used as a genetic marker for SLE susceptibility in Thai populations. In addition, the -863A genotype could produce high TNF levels and potentially induce the occurrence of Raynaud's phenomenon.     

Immunocompromised group differences in the presentation of intestinal strongyloidiasis

The hospital records of 213 outpatients from Bangkok, Thailand, infected with Strongyloides stercoralis as determined by stool inspections were examined retrospectively for the different clinical presentations ascribed to patients with HIV, those with chronic illness, those who used immunosuppressant drugs and relatively healthy subjects. For HIV patients with strongyloidiasis, the most common symptoms were chronic diarrhea, fever, persistent coughing and loss of weight, but only the first three symptoms were significantly different from other immunocompromised hosts. For healthy patients with strongyloidiasis, acute diarrhea and abdominal pain were the most frequent symptoms. Moreover, the peripheral eosinophil blood count was significantly lower (P=0.004) in the HIV patients than in any of the other subsets. Males were more common than females across all categories. While the average age of all subjects was 48.3+/-16.4 years, the strongyloidiasis patients with chronic illness were significantly older (56.8+/-13.5 years) than those in the other groups. This study may suggest that strongyloidiasis is commonly found in geriatric males, and that the patients most at risk for S. stercoralis infection are HIV patients. This is the first report of the different clinical presentations of intestinal strongyloidiasis in various groups of patients with impaired immunity.     

Impact of the heterozygous TPMT*1/*3C genotype on azathioprine-induced myelosuppression in kidney transplant recipients in Thailand

Background: Thiopurine S-methyltransferase (TPMT) is a polymorphic enzyme associated with detoxification of azathioprine, an immunosuppressant used after renal transplantation in several Asian countries. Patients with variations of the TPMT gene may be at risk for myelosuppression after they receive a standard dosage of the drug. The frequency of TPMT*3C has been reported to be higher in the Thai population than in other Asian populations, possibly putting the Thais at higher risk for myelosuppression.Objective: The aim of this study was to assess the impact of the heterozygous TPMT*1/*3C genotype on azathioprine-induced myelosuppression in kidney transplant recipients in Thailand.Methods: This study was conducted at Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand, and Chulalongkorn Hospital, Chulalongkorn University, Bangkok, Thailand. Eligible patients underwent kidney transplantation from deceased or living-related donors from 1984 to 2007. Electronic medical records were assessed retrospectively for the 6-month period after initiation of azathioprine treatment. TPMT genotyping and phenotyping were studied prospectively using real-time polymerase chain reaction and biochemical assay, respectively. The odds ratios (ORs), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined.Results: A total of 139 patients were enrolled (89 men, 50 women; median age, 42 years [range, 17–70 years]; mean weight, 58 kg [range, 37–87 kg]). The heterozygous TPMT*1/*3C genotype was found in 9 of the 139 patients (6.47%) (95% CI, 3.00–11.94). The TPMT activity of those patients was significantly lower than that of patients with the homozygous wild-type genotype (median, 21.37 vs 37.12 nmol 6-methylthioguanine/g · Hb/h, respectively; P < 0.001). The risk for azathioprine-induced myelosuppression in the patients with the heterozygous TPMT*1/*3C genotype was significantly higher than that in patients with the wild-type genotype (adjusted OR, 14.18 [95% CI, 3.07–65.40]; P < 0.005). The sensitivity and specificity of TPMT*3C genotyping for the prediction of azathioprine-induced myelosuppression in these kidney transplant recipients were 27% and 97%, respectively. Assuming a prevalence of azathioprine-induced myelotoxicity of 7% according to previously published data, the PPV and NPV were estimated to be 50% and 95%, respectively.Conclusion: In these kidney transplant recipients, patients who carried the TPMT*3C allele were at a higher risk for azathioprine-induced myelosuppres-sion than noncarriers.     

Role of Gastrointestinal Microbiota on Kidney Injury and the Obese Condition

Obesity is associated with kidney disease, probably due to obesity-mediated inflammation, podocyte injury and oxidative stress in the kidney It is also linked to other diseases, for example, diabetes and hypertension, which are associated with the development and progression of chronic kidney disease. Interestingly, gastrointestinal dysbiosis has been demonstrated in cases of obesity with the development and progression of kidney disease. Thus, modification of gastrointestinal microbiota using probiotics or prebiotics or both to improve the balance of bacterial flora is a potential approach for the management of obesity-associated kidney disease. This review covers information regarding the association between obesity and kidney injury, and it examines evidence for a hypothesized role of gastrointestinal microbiota in this setting. Studies describing the effects of probiotic and prebiotic treatments on kidney disease show mixed results, although several suggest benefits indicated by biomarkers associated with kidney injury, uremia and inflammation. Additional studies are needed to determine whether these interventions are clinically effective in managing kidney injury and kidney disease.     

Leptin, soluble leptin receptor, lipid profiles, and LEPR gene polymorphisms in Thai children and adolescents

OBJECTIVE: To evaluate the relationships between leptin, soluble leptin receptor, lipid profiles, and LEPR gene polymorphisms in child and adolescent Thai subjects. DESIGN: Cross-sectional study of Thai children and adolescents. SUBJECTS: 116 male and 65 female at risk for overweight/overweight child and adolescent Thai subjects, and 33 male and 62 female healthy child and adolescent Thai subjects (age: 5-19 years). MEASUREMENTS: Leptin levels, soluble leptin receptor levels, lipid profiles, LEPR gene polymorphisms. RESULTS: Significantly higher levels of cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), and leptin levels were observed in at risk for overweight/overweight group. On the other hand, high-density lipoprotein cholesterol (HDL-C) and soluble leptin receptor levels were significantly lower in the same group. Serum soluble leptin receptor levels were significantly negatively correlated with leptin. The at risk for overweight/overweight subjects with the Lys656Lys homozygous wild type LEPR gene had significantly higher cholesterol and LDL-C levels than those with Lys656Asn heterozygous and Asn656Asn homozygous mutant type. In contrast, subjects with Lys656Lys homozygous wild type had significantly lower leptin levels than those with Lys656Asn heterozygous and Asn656Asn homozygous mutant type. There was a statistically significant association between body mass index (BMI) and hyperleptinemia (odds ratio; OR = 2.49, p = 0.000) and females had more increased risk of hyperleptinemia than males (OR = 15.74, p = 0.004) in adolescent Thai subjects. CONCLUSION: The present study is the first report of Lys656Asn polymorphism of the LEPR gene associated with cholesterol, LDL-C, and leptin levels in Thai children and adolescents. Serum leptin levels were significantly higher in the at risk for overweight/overweight. In contrast, there were significantly lower soluble leptin receptor levels in the same group. In addition, there was a statistically significant association between BMI, sex, and hyperleptinemia in adolescent Thai subjects.     

Concordance of skin prick test and serum-specific IgE to locally produced component-resolved diagnostics for cockroach allergy

Background

Diagnosis of Periplaneta americana (American cockroach, ACR) allergy is commonly performed based on clinical history and skin prick test (SPT) or specific serum IgE (sIgE) measurement. The concordance of the findings with the SPT and sIgE results has never been investigated.