Genetic polymorphisms of 21 autosomal STR loci in Chinese Uygur ethnic population.

Genetic polymorphisms of 21 short tandem repeat (STR) loci were studied in 576 unrelated Uygur individuals living in Urumqi using Goldeneye™ DNA ID 22NC system. Population data of all loci, except one locus (D1S1656), had no significant deviation from Hardy-Weinberg equilibrium. A high degree of genetic polymorphisms was showed by all STR loci in Urumchi Uygur population. The combined power of discrimination (CPD) was 0.999999999999999999999999985256 and the combined power of exclusion (CPE) was 0.999999997207836. In addition, we performed comparisons between the data from Uygur population with previously published data obtained from other populations.

The prevalence and clinical profiles of FLT3-ITD, FLT3-TKD, NPM1, C-KIT, DNMT3A, and CEBPA mutations in a cohort of patients with de novo acute myeloid leukemia from southwest China.

While a substantial amount of data on gene mutations related to acute myeloid leukemia (AML) prognosis from western and other populations have been reported, these studies largely describe one or two genes. Additionally, in southwest China, only insufficient data exist regarding FLT3-ITD, FLT3-TKD, NPM1, C-KIT, DNMT3A, and CEBPA mutations have been widely used in clinical settings. Therefore, a comprehensive study about these mutations of clinical importance in the prognosis of AML in western China is necessary. In a cohort of 255 patients with de novo AML, we retrospectively analyzed the prevalence of the six gene mutations, and then we assessed the results in conjunction with clinical characteristics and treatment responses. As for the frequencies of these mutations, the NPM1 mutation occurred most frequently (17.7 %; 42/237), followed by the CEBPA mutation (15.0 %; 19/127) and the FLT3-ITD mutation (10.2 %; 25/244). The frequencies of the FLT3-TKD, DNMT3A, and C-KIT mutations were 3.7 % (9/234), 4.0 % (9/225) and 4.2 % (10/238), respectively. These mutations were closely related to clinical characteristics including FAB classification, gender and age, hemogram, blasts (%), fusion genes, and immunophenotypes. Additionally, a higher complete remission (CR) rate was found in NPM1-mutated patients. The occurrence of these mutations is variable among different countries and regions worldwide, which may provide clues to the etiology of AML. Besides, we identified new clinical characteristics that advance our understanding of these mutations and further clarify the involvement of these mutations in the development of leukemia.

ARID5B Genetic Polymorphisms Contribute to the Susceptibility and Prognosis of Male Acute Promyelocytic Leukemia.

This study was conducted using TagSNPs to systematically explore the relationship between ARID5B polymorphisms and the occurrence, clinical characterization, and prognosis of acute myeloid leukemia (AML). A total of 569 unrelated AML patients and 410 healthy individuals from West China were recruited, and ARID5B TagSNPs were genotyped using iMLDR® (improved multiplex ligation detection reaction). It was found that the association of ARID5B polymorphisms with AML was most significant in acute promyelocytic leukemia (APL), and exclusively in males, the mutant alleles of rs6415872, rs2393726, rs7073837, rs10821936, and rs7089424 were found to increase the risk of developing APL in men, the odds ratio (OR) were 1.36, 1.74, 1.45, 1.53, and 1.56 (all p < 0.05), respectively. Haplotype analysis revealed that haplotype [AACCG] increased the risk of male APL with an OR of 1.53 (95% confidence interval: 1.10-2.14, p = 0.012). Besides, there was a strong positive additive interaction between rs6415872 and rs10821936, rs7089424, respectively, and cases attributed to the interaction of rs6415872, rs10821936, and rs7089424 accounted for 100%. Furthermore, ARID5B single nucleotide polymorphisms were found associated with clinical features of AML, and rs6415872 was shown to be an independent prognosis factor in APL patients. Besides, dual luciferase report assay showed that rs6415872 may affect the binding activity of PPARG with ARID5B. ARID5B polymorphisms contribute to male APL risk, clinical feature, and prognosis, suggesting the importance of ARDI5B in AML pathogenesis and development, and the gender and subtype preference may prompt some specific mechanisms of ARID5B. Besides, ARID5B polymorphisms might be a potential prognosis biomarker.

Sequence variations of mitochondrial DNA D-loop region in patients with acute myeloid leukemia.

The aim of the present study was to explore variations of the displacement (D)-loop region in patients with acute myeloid leukemia (AML) and their possible associations with AML pathogenesis. Blood or bone marrow samples from 216 patients with AML (158 AML patients in the first stage, and 58 more patients with AML-M3 for further verification), and 146 healthy controls were collected. Sanger sequencing was performed for the D-loop region ranging between nucleotide (nt)15811 and nt 775. With the exception of mitochondrial microsatellite instability (mtMSI) variations, a total of 2,630 variations in 232 loci were identified with similar variation rates/person in patients with AML and controls when compared with the revised Cambridge reference sequence (8.54±2.14 vs. 8.77±2.15; P=0.366). A positive association between AML and variation-T152C was identified, which occurred more frequently in patients with AML compared with in controls [26.6 vs. 17.1%; P=0.048; odds ratio (OR), 1.752; 95% confidence interval (CI), 1.004-3.058]. Furthermore, T152C was identified to be associated with promyelocytic leukemia-retinoic acid receptor α(PML-RARα) and French-American-British AML subtypes, with a tendency to occur in patients with AML-M3. The AML-M3 sample size was extended by 58 cases, and it was identified that the T152C variation rate was significantly higher in patients with AML-M3 compared with that of controls (41.0 vs. 17.1%; P<0.001; OR, 3.228; 95% CI, 1.714-6.079). However, no association was identified between the T152C variation and clinical characteristics, or chemotherapy response in patients with AML-M3. In addition, the mtMSIs, including D310, mt514-523 (CA)n and T16189C, demonstrated no association with AML risk. Together, the results of the present study suggest that the mitochondrial DNA D-loop region is high variable, and that T152C is associated with AML risk, particularly regarding the M3 subtype. T152C mayparticipate in AML pathogenesis and may be a diagnostic biomarker; however further studies with larger sample sizes are required in order to verify its value.

Status of drug-resistant tuberculosis in China: A systematic review and meta-analysis.

BACKGROUND: We conducted a systematic review and meta-analysis on drug-resistant tuberculosis in China to provide useful data for tuberculosis (TB) surveillance and treatment. METHODS: Several databases, including PubMed, Embase, and the Chinese Biological Medical Database, were systematically searched between January 1, 1999, and August 31, 2015, using strict inclusion and exclusion criteria. RESULTS: The corresponding drug-resistant TB prevalence between the new and previously treated cases was significantly different in almost all of the economic regions. The Eastern coastal region is the most developed economic region with the lowest total drug-resistant TB prevalence (any drug resistance: 28%; 95% confidence interval [CI], 25%-32%; multidrug resistance: 9%; 95% CI, 8%-12%) and the lowest number of new cases (any drug resistance: 21%; 95% CI, 19%-23%; multidrug resistance: 4%; 95% CI, 3%-5%). The Northwest is the least developed area with the lowest drug-resistant TB prevalence for previously treated cases (any drug resistance: 45%; 95% CI, 36%-55%; multidrug resistance: 17%; 95% CI, 11%-26%). The prevalence (multidrug and first-line drug resistance) exhibited a downward trend from 1996-2014. The extensively drug-resistant prevalence in China was 3% (95% CI, 2%-5%) in this review. CONCLUSIONS: Overall, the status of drug-resistant tuberculosis in China is notably grim and exhibits regional epidemiologic characteristics. We are in urgent need of several comprehensive and effective control efforts to reverse this situation.

Clinical features, Outcomes and Molecular Profiles of Drug Resistance in Tuberculous Meningitis in non-HIV Patients.

Tuberculous meningitis continues to be a serious problem for physicians because it is difficult to make an early diagnosis and the consequences of delaying treatment are severe. The objective of this study is to provide data for the optimization of diagnostic and timely treatment of tuberculous meningitis. Of the 401 human immunodeficiency virus (HIV)-negative tuberculous meningitis patients in our study, 332 were found to have an impaired blood brain barrier (82.8%). Nearly 17.0% of patients failed to be timely diagnosed. Headache (53.6%) and fever (48.6%) were the most common features, and Computed Tomography/Magnetic Resonance Imaging (CT/MRI) detected 96 patients (23.9%) with abnormal meningeal imaging. Cerebrospinal fluid real-time polymerase chain reaction was positive in 73.8% of the tuberculous meningitis patients, whereas, smears and cultures detected only 6.7% and 5.2%, respectively. Further analysis identified striking differences between drug-resistant and drug-susceptible tuberculous meningitis. Patients with drug resistance correlated with grave prognosis. Tuberculous meningitis diagnosis should overall embody clinical symptoms, laboratory and cerebral imaging findings, and more sensitive diagnostic approaches are still warranted. Our data suggest cerebrospinal fluid polymerase chain reaction for mycobacterial DNA and molecular drug susceptibility testing as routine assays for suspected tuberculous meningitis patients, and observation of the blood brain barrier function could be performed for individual management.