title: Gene polymorphisms in CCR5, CCR2, SDF1 and RANTES among Chinese Han population with HIV-1 infection.
abstract: Chemokines and chemokine receptors are crucial for immune response in HIV-1 infection. Although many studies have been done to investigate the relationship between chemokines and chemokine receptor gene polymorphisms and host's susceptibility to HIV-1 infection, the conclusions are under debate. In the present study, a cohort of 287 HIV-1 seropositive patients, 388 ethnically age-matched healthy controls and 49 intravenous drug users (IDUs) HIV-1 exposed seronegative individuals (HESN) from Chinese Han population were enrolled in order to determine the influence of host genetic factors on HIV-1 infection. Seven polymorphisms on four known chemokines/chemokine receptor genes (CCR5Δ32, CCR5 m303, CCR5 59029A/G, CCR2 64I, RANTES -403A/G, RANTES -28C/G and SDF1 3'-A) were screened. CCR5Δ32 and CCR5 m303 were absent or infrequent in Chinese Han population, which may not be hosts' genetic protective factors for HIV-1 infection. Our results showed the CCR5 59029A/G, CCR2 64I and SDF1 3'-A were not associated with host's resistance to HIV-1 infection. The frequency of RANTES -403A allele was significantly lower in HIV-1 patients than in healthy blood donors (p=0.0005) and HESN group (p=0.035), which implied the association between A allele and reduced HIV-1 infection risk. Different genetic models were assessed to investigate this association (AA vs. GG+AG, OR=0.38 95% CI, 0.22-0.65 p=0.0004; A vs. G, OR=0.66 95% CI, 0.52-0.84 p=0.0006), which supported this association, either. The genotype and allele distribution of RANTES -28 between HIV-1 patients and healthy controls (genotype profile: p=0.072; allele profile: p=0.027) or HIV-1 seronegative group (genotype profile: p=0.036; allele profile: p=0.383) were both at the marginal level of significance, which were not observed after Bonferroni correction. All these results suggest the RANTES -403A may be associated with reduced susceptibility to HIV-1 infection, while the RANTES -28 locus not. By lack of the patients' clinical information, whether these polymorphisms affect AIDS disease progression and their role in different HIV-1 infection routes could not performed in present study and needs to be assessed in ongoing studies.
authors.affiliation: Department of Genetics and Developmental Biology, Southeast University School of Medicine, Nanjing 210009, China; The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Southeast University, Nanjing 210096, China. Electronic address: lihui19801019@gmail.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Life Sciences, The Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096, China. Electronic address: liutingjun222@163.com.
authors.forename: Ting-Jun
authors.initials: TJ
authors.lastname: Liu
authors.affiliation: Department of Genetics and Developmental Biology, Southeast University School of Medicine, Nanjing 210009, China; The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Southeast University, Nanjing 210096, China. Electronic address: hongzehui@seu.edu.cn.
authors.forename: Ze-Hui
authors.initials: ZH
authors.lastname: Hong
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics*; D000328:Adult; D018946:Chemokine CCL5 / Q000235:genetics*; D054377:Chemokine CXCL12 / Q000235:genetics*; D002681:China; D018450:Disease Progression; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006679:HIV Seropositivity; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054390:Receptors, CCR2 / Q000235:genetics*; D019713:Receptors, CCR5 / Q000235:genetics*; D055815:Young Adult
chemical_list: C483024:CCL5 protein, human; C515334:CCR2 protein, human; C584933:CCR5 protein, human; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D054390:Receptors, CCR2; D019713:Receptors, CCR5
keywords: Chemokine receptors; Chemokines; Genetic association; HIV-1; Polymorphism