Study On The Associations Between Polymorphism Of SDF1-3’A、CCR2-64I、RANTES-In1.1C And Efficacy Of HAART

Background and ObjectiveAIDS (Acquired Immune Deficiency Syndrome, AIDS) is a kind of infected disease composed of people infected with the human immunodeficiency virus, causing great harm and high mortality. Highly active antiretroviral therapy (Highly Active Antiretroviral Therapy, HAART) is used in combination by three or more antiviral drugs to treat AIDS approach proposed by the Chinese-American scientist David Ho in1996, is to extend the patient life and improve the quality of life and reduce major route of HIV transmission. In country currently, the first-line antiretroviral therapy free AIDS drugs are primarily nucleoside reverse transcriptase inhibitors (Nucleoside reverse transcriptase inhibitors, NRTIs) and non-nucleoside reverse transcriptase inhibitors (Non Nucleoside reverse transcriptase inhibitors, NNRTIs), while the second line drugs are mainly protease inhibitors (Protease Inhibitors, PIs) which is on the basis of the first-line drugs.but all the subjects of the study area have received national first-line regimens prescribed drugs. With the widespread implementation of HAART, the treatment effect increasing cause for concern, HAART efficacy varies with different patients after antiretroviral therapy, the impact of HAART efficacy in many reasons, has a clear effect of the factors associated with HAART adherence in addition to the differences, HIV mutation and individual variability of age endures, genetic factors also can not be ignored. Studies have shown that host cells of people with AIDS-related gene polymorphisms on the disease process will have an extended of impact:Stromal cell-derived factor (Stromal-Derived Factor1, SDF1) is a chemokine receptor which located in10q11.21, the3’untranslated region of the first801G�'A (SDF1-3’A), can significantly delay AIDS disease progression,However Mummidi et studies suggest that the homozygous loci promote the morbidity and mortality of infected persons;CC chemokine receptors-2’(CC chemokine receptor2, CCR2) which located in3p21.31, It’s G�'A mutation (CCR2-64I) positioned at190nucleotide open reading frame after the ATG start site, can delay disease progression of AIDS; Regulated on activation, normal T cell expressed and secreted factors (Regulated upon Activation Normal T cell Expressed and Secreted factor, RANTES) are one of three chemokine of CD8+T lymphocytes releases located in17q11.2-q12, the non-coding region of the gene first intron T�'C mutation (RANTES-Inl.1C) can delay disease progression of AIDS. Due to differences in regional races, the impact of these factors on the progress of AIDS produced inconclusive. Research on the above three factors and disease progression of HIV infection related to relatively large, but the influence of these factors on the efficacy of HAART AIDS produced relatively rare.HAART efficacy study on sexually transmitted population of Europe by Hendrickson showing that SDF1-3’A. CCR2-64I and RANTES-Inl.1C were associated with reduced efficacy of HAART. AIDS infected in Henan prvince mostly dominated apheresis plasma, and different routes of infection can also cause different genetic subtypes of the HIV infection, recent reports indicate that the disease process route of infection might be affected, Compared with other ways of getting infected populations, populations of sexually transmitted disease process is relatively fast. The number of people infected with HIV in Henan Province is large, the total number of people receiving antiretroviral therapy is the first most in our country, so, study on HAART efficacy correlation of populations in this region is very meaningful.This research had have tests and analysis on the sits CCR2-64I, SDF1-3’A, RANTES-Inl.1C of people with antiretroviral treatment for three years in Henan Han with methods of PCR (Polymerase Chain Reaction, PCR) and gene sequencing on AIDS patients, aiming to ascertain the relationship of CCR2-64I, SDF1-3’A, RANTES-Inl.1C polymorphisms and AIDS HAART efficacy of antiviral therapy for the analysis of the reasons for the failure, clinical antiviral therapy and to provide evidence for develop personalized treatment programs.Materials and MethodsAccording to the China Center Disease Control and Prevention (Center for Disease Control and Prevention, CDC) developed the "China AIDS antiretroviral treatment information system", we collected blood samples of people receive free Henan AIDS antiretroviral treatment for three years in parts of the country to test CD4+T lymphocyte, And with reference to pre-treatment baseline CD4, according to "national free antiretroviral treatment of AIDS Handbook" on the immunological treatment evaluation criteria, the CD4+T lymphocyte levels equal to or lower than the baseline group were classified as invalid, a total of52cases were male30cases,22females, aged48.54±8.51years old,43cases of blood-borne and sexually transmitted nine cases; CD4+T lymphocytes in the treatment baseline levels higher than those classified as valid group, a total of156cases, including67males and females89patients aged46.93±8.88years old, blood-borne117cases,39cases of sexual transmission.All patients enrolled are older than18years, with good previous medication compliance, and taking only the free distribution of national unity HIV antiretroviral therapy program provides first-line drugs, while excluding HIV genotypic drug resistance, Hepatitis B, Syphilis, Hepatitis C, Tuberculosis and autoimmune functional deficiency diseases. The gender, age and initial baseline CD4treatment and other basic data matches well (p>0.05) between the two groups.All selected objects are signed informed consent, collect and detect2ml anticoagulated whole blood CD4+T lymphocytes, genomic DNA, according to the three gene amplification rs code use Primer5.0design specific primers, PCR amplification of the host the purpose of gene DNA fragments amplified positive products of all companies send invitrogen purified and sequenced, sequencing results by stitching, proofreading and gene Bank after the original sequence analysis to determine the genotype.All the result of genotype test were entry Excel spreadsheet, using online analysis software application SHEsis HW (Hardy-Weinberg) to have equilibrium test, genotype and allele analysis; using SPSS170software basic patient information for analytical processing, data significantly between the groups. In differences and different genetic models (additive, dominant and recessive) genotype comparison using the chi-square test, and calculate the odds ratio (OR value) and95%confidence interval (CI), P<0.05was statistically significance.Results:1.In additive mode, SDF1-3’A sites in invalid group and valid group GA genotype frequency difference was not statistically significant (P=0.939), A A genotype frequencies in the invalid group (15.4%) was significantly higher t he valid group (3.8%), the difference was statistically significant (P=0.005), with GG genotype as a reference, with AA genotype, the risk of failure of ant iviral therapy to improve (OR=4.593,95%CI:1.446-14.388); AA genotype fr-equencies recessiveness mode invalid group and valid group were15.4%and3.8%, the genotype frequencies with statistical difference between the two groups (p=0.011), the relative risk analysis showed that in GG/GA genotype as a reference, with AA genotype antiviral increased risk of treatment failure (OR=4.545,95%CI:1.497-13.800); dominant mode in the two-locus genotype fr equencies no significant difference between the groups. For CCR2-64I and RA NTES-In1.1C sites in the additive, dominant and recessive mode of analysis, t he two-point difference in genotype frequencies were not statistically valid gro up and valid group.2. Allele frequency of SDF1-3’A A in the invalid group (31.7%) is higher than the valid group (21.7), P=0.048, as a reference to the G allele, carryi ng anti-A allele increased risk of virologic failure, OR=1.063,95%CI of (1.001-2.667); CCR2-64I and RANTES-Inl.1C each locus allele frequency was no significant difference between the valid and invalid group.3.sex stratified analysis showed that:in the male population, invalid group,AA genotypes and A allele frequency of SDFl-3’A was significantly higher t han the valid group (16.7%vsl.5%,35.0%vs20.9%), the difference was stati stically significant (p=0.016and P=0.037), carrying SDF1-3’A AA genotyp es and a allele antiviral treatment failure increased risk (OR=14.286,95%CI:1.534-133.072, OR=2.038,95%CI:1.038-4.001); while in the female pop ulation, no significant difference SDF1-3’A AA genotypes and a allele frequenc ies between the inactive group and valid group (P=0.248; P=0.555). After analyzing the site of CCR2-64I and RANTES-Inl.1C in men and women in valid and invalid group, no significant difference about genotype and allele fr equencies were found between the two groups.4. Analyzing on people infected by blood, genotype and allele of SDF1-3’ A and CCR2-64I and RANTES-Inl.1C was found in both groups, genotypes of AA and allele of A frequency in SDF1-3’A in invalid group was significa ntly higher than the valid group (18.6%vs5.1%;36.0%vs23.5%), the differen ce was statistically significant (p=0.018and P=0.025); AA genotypes and a allele risk individuals can improve antiviral treatment failure (OR=4.533,95%CI:1.407-14.607; OR=1.834,95%CI:1.076-3.129). Genotype and allel e frequencies of CCR2-64I and RANTES-Inl.1C in blood infected people were not statistically different between the two groups.ConclusionsPolymorphisms of SDF1-3’A and efficacy of AIDS HAART are related, AA genotypes and allele of SDF1-3’A are failure risk factors of antiretroviral treatment in Henan Han population, especially in men and menstrual blood infected population.