Novel Association between Flavin-Containing Monooxygenase 3 Gene Polymorphism and Antithyroid Drug-Induced Agranulocytosis in the Han Population.

Some effective antithyroid drugs (ATDs) have been widely used for patients with Graves' disease (GD) but are associated with ATD-induced agranulocytosis. We selected 29 ATD-induced agranulocytosis patients, 44 ATD-induced neutropenia patients, and 140 GD controls among the Chinese Han population who were recruited at the First Affiliated Hospital of Xi'an Jiao Tong University. We assessed their response to ATDs treatment by performing genotyping for a candidate gene association study of samples from patients receiving treatment. Human flavin-containing monooxygenase 3 (FMO3), which is the major hepatic enzyme involved in the production of N-oxide of trimethylamine, catalyzes the oxygenation of a variety of drug compounds. Six single SNP, genotype, haplotype (HAP), and association analyses of the FMO3 gene with ATD-induced agranulocytosis/neutropenia under different models (i.e., additive, dominant, and recessive models) were performed. Rs1736557, which caused an amino acid variation V257M, showed a strong association between ATD-induced agranulocytosis and GD controls after Bonferroni correction (p = 0.011, OR 2.301, 95% CI 1.201-4.409). The presence of HAP 3 (HAP3) in the FMO3 gene HAP was statistically associated with ATD-induced agranulocytosis (p = 0.038, permutation p value). Our findings indicate that genetic variations in the FMO3 gene are associated with the response to ATDs maintenance treatment in ATD-induced agranulocytosis patients of -Chinese Han population.

Association of KCNJ11 and ABCC8 genetic polymorphisms with response to repaglinide in Chinese diabetic patients.

AIM: The aim of this study was to investigate the association of KCNJ11 E23K and ABCC8 exon16-3T/C with the therapeutic effect of repaglinide in patients with type 2 diabetes. METHODS: A total of 100 Chinese patients with newly diagnosed type 2 diabetes were treated with repaglinide for 24 weeks. Arginine stimulation tests were performed to evaluate beta cell function. Gene variations were detected with PCR-restriction fragment length polymorphism. Responders were defined by a greater than 25% decrease in fasting plasma glucose or a greater than 20% decrease in hemoglobin A1c (HbA1c) values (or both) after the 24 week repaglinide treatment. RESULTS: Both baseline HbA1c and the decrease of HbA1c were significantly higher in patients with E/K and K/K genotypes of the KCNJ11 E23K variant when compared with E/E homozygotes (P=0.0103 and 0.0221, respectively). The decrease in 2 h postprandial plasma glucose (2hPG) was significantly greater in E/K heterozygotes than E/E homozygotes (P=0.0367). There was a significant difference in the response rate to repaglinide treatment between the E and K alleles (68% vs 82%, P=0.0324). The changes in fasting insulin and the homeostasis model assessment of insulin resistance were significantly greater in patients with ABCC8 exon16-3 C/C versus the T/C and T/T genotypes (P=0.0372 and 0.0274, respectively). CONCLUSION: The KCNJ11 E23K variant was associated with the therapeutic effect of repaglinide. In addition, The C/C homozygotes of the ABCC8 exon16-3T/C variant responded better to repaglinide in insulin sensitivity than the T/C and T/T genotypes.

Efficacy of first-line chemotherapy affects the second-line setting response in patients with advanced non-small cell lung cancer.

BACKGROUND: Chemotherapy is the mainstay of treatment for the majority of patients with advanced non- small cell lung cancer (NSCLC) without driver mutations and many receive therapies beyond first-line. Second- line chemotherapy has been disappointing both in terms of response rate and survival and we know relatively little about the prognostic factors. MATERIALS AND METHODS: One thousand and eight patients with advanced NSCLC who received second-line chemotherapy after progression were reviewed in Shanghai Pulmonary Hospital, China, from September 2005 to July 2010. We analyzed the effects of potential prognostic factors on the outcomes of second-line chemotherapy (overall response rate, ORR; progression free survival, PFS; overall survival, OS). RESULTS: The response and progression free survival of first-line chemotherapy affects the ORR, PFS and OS of second-line chemotherapy (ORR: CR/PR 15.4%, SD 10.1%, PD2.3%, p<0.001; PFS: CR/PR 3.80 months, SD 2.77 months, PD 2.03 months, p<0.001; OS: CR/PR 11.60 months, SD 10.33 months, PD 6.57 months, p=0.578, p<0.001, p<0.001, respectively). On multivariate analysis, better response to first-line therapy (CR/PR: HR=0.751, p=0.002; SD: HR=0.781, p=0.021) and progression within 3-6 months (HR=0.626, p<0.001), together with adenocarcinoma (HR=0.815, p=0.017), without liver metastasis (HR=0.541, p=0.001), never-smoker (HR=0.772, p=0.001), and ECOG PS 0-1 (HR=0.745, p=0.021) were predictors for good OS following second- line chemotherapy. CONCLUSIONS: Patients who responded to first-line chemotherapy had a better outcome after second-line therapy for advanced NSCLC, and the efficacy of first-line chemotherapy, period of progression, histology, liver metastasis, smoking status and ECOG PS were independent prognostic factors for OS.

[Metabolic syndrome and chronic kidney disease in a rural adult population of Hunan province, China].

OBJECTIVE: To explore the relationship between metabolic syndrome and chronic kidney disease (CKD) in a rural adult population of Hunan province. METHODS: 1953 residents (older than 18 years) from the same village were randomly selected, using a stratified, multistage sampling method. All residents were interviewed and tested for albuminuria with morning spot urine albumin to creatinine ratio (abnormal: >/= 30 mg/g), reduced renal function with estimated glomerular filtration rate by modified MDRD equation [abnormal: < 60 ml/min (1.73 m(2))]. The associations of kidney damage indicators with demographic characteristics (age, gender, smoking status), indicators on health (diabetes, hypertension) and metabolic syndrome traits were examined. RESULTS: Eligible data of 1709 subjects were enrolled in the study. After the adjustment of age, gender and other metabolic syndrome traits, participants with metabolic syndrome had a higher prevalence of CKD (19.3% vs. 13.2%, P < 0.001) than those without the syndrome. As the number of metabolic syndrome traits increased, so did the prevalence of CKD. There seemed to be a strong and independent association between metabolic syndrome and chronic kidney disease. For participants without hypertension and diabetes, metabolic syndrome was also associated with CKD (OR value 1.733, 95%CI: 1.20 - 2.41, P = 0.004). CONCLUSION: In these 1709 adults under this study from a village of southern China, metabolic syndrome seemed to be associated with CKD.