Association of polymorphisms of cytosine arabinoside- metabolizing enzyme gene with therapeutic efficacy for acute myeloid leukemia

Background The cytosine arabinoside （Ara-C）-based chemotherapy is the major remedial measure for acute myeloid leukemia （AML）. Deoxycytidine kinase （DCK） and cytidine deaminase （CDA） are the key enzymes in the metabolism of Ara-C. Many single nucleotide polymorphisms （SNPs） and haplotypes of DCK and CDA, which contribute to susceptibility to Ara-C, have been identified in Africans and Europeans. However, there has been no report about the relation among three SNPs in DCK （rs115543896, rs72552079, and rs111454937） and two SNPs in CDA （rs2072671 and rs60369023）, and their clinical response to Ara-C for a Chinese population. In this study, we aimed to investigate whether these five SNPs are associated with the therapeutic outcomes of Ara-C-based chemotherapy regimens in patients with AML. Methods A total of 151 Chinese patients with AML were enrolled in our study. SNPs genotyping were performed using the MassARRAY system by means of the matrix-assisted laser desorption ionization-time of flight mass spectrometry （MALDI-TOF-MS） method. Results The results illustrated that DCKrs111454937 AA genotype was more frequent in patients with higher platelet count, and A allele frequency was significantly higher in the group 〈40 years, lower white blood cell （WBC） count patients group and the group with platelet counts 〉60xl0e/L. Meanwhile, both DCKrs72552079 TC （OR=1.225, 95% C1=1.225-9.851, P=0.0192） and CDArs60369023 GA （OR=9.851,95% C1=1.31-77.93, ,~=-0.0263） significantly improved Ara-C-based chemotherapy response. While DCKrs11554389 AA （OR=0.147, 95% CI=0.027-0.801, P=0.0267） was associated with the decrease of Ara-C-based chemotherapy response. Conclusion It is evident that the DCK and CDA polymorphisms might be the important markers for the AML patients＇ therapy outcomes in a Chinese population.

Association between Drug Co-use Networks and HIV Infection:A Latent Profile Analysis in Chinese Mainland

Persons who use drugs are a high-risk subpopulation for HIV infection because more than one drug user often take drugs together,which increases the risk of HIV transmission.For the PWUDs who had tested for HIV,we extracted data on demographic characteristics,drug types,injection drug use behavior,encrypted IDs of co-users,and drug use location from the National Dynamic Management and Control Database for Persons Who Use Drugs between January 2008 and July 2016.We mapped and classified Co-UDs’networks and estimated the risk of HIV infection.Drug co-use networks were formulated on the basis of connections between PWUDs at the same time and location.Latent profile analysis(LPA)and logistic regression models were used to cluster the classes and to estimate the HIV infection risk among them,respectively.A total of 470967 PWUDs were included,among whom 69529 Co-UDs formed 7001 networks,which were categorized into three classes:Class A(n=211,3.0%)had large networks,with more members(median 10.0(IQR:8.0-14.5)),and comprised depressant and stimulant users located in central and eastern China;Class B(n=3770,53.8%)was dominated by depressant users(median 3.0(IQR:3.0-4.0))across the country;Class C(n=3020,43.1%)was dominated by stimulant users(median 3.0(IQR:3.0-4.0))located in central and eastern China.The HIV infection rates were 9.71%,3.33%,and 0.33%in Classes A,B,and C,respectively.Compared with Class A,Classes B and C were associated with decreased odds of HIV infection.Our findings suggest that more attention should be paid to larger networks,with a relatively high HIV infection risk,to enhance prevention and intervention strategies.