title: Genetic variations in cytotoxic T-lymphocyte antigen-4 and susceptibility to cervical cancer.
abstract: Cytotoxic T-lymphocyte antigen-4 (CTLA-4), a molecule expressed predominantly on activated T cells, plays an important role in the down-regulation of T-cell activation. To evaluate the potential effects of CTLA-4 gene polymorphisms on susceptibility to cervical cancer, we genotyped polymorphisms in CTLA-4 (- 318 T/C, CT60 G/A,+49 G/A, - 658 T/C, and - 1661 G/A) and calculated odds ratios for the genotype and allele distributions between patients and controls. We then examined the functional relevance of the polymorphisms using enzyme-linked immunosorbent assays (ELISAs), in vitro lymphocyte proliferation assay, and cytotoxic assay. The CTLA-4 - 318 CC, CT60 AA, and+49 GG genotype frequencies were lower in patients than in controls (p <0.05). The frequencies of CTLA-4 - 318 T allele and CT60G allele carriers were significantly higher in patients than in controls (p <0.05). Upon stimulation, peripheral blood mononuclear cells (PBMCs) carrying the - 318TT and CT60GG genotypes exhibited significantly lower proliferation, IL-2, and IL-4 levels; fewer cytolytic activities; and higher TGF-β levels compared with PBMCs carrying the - 318 CC/CT or CT60 AA/AG genotypes. We also found that CTLA-4 - 318 T/C and CT60 G/A single nucleotide polymorphisms were associated with the severity of cervical cancer. These results indicate that CTLA-4 - 318 T/C and CT60 G/A can affect cervical cancer susceptibility by altering the immune status of an individual.
authors.affiliation: Wuhan University Health Sciences Center, Wuhan 430071, Hubei, China; Department Of Gynecology and Obstetrics, People's Hospital of Jiangxi Province, Nanchang 330006, Jiangxi, China.
authors.forename: Yuan-Huan
authors.initials: YH
authors.lastname: Xiong
authors.affiliation: Wuhan University Health Sciences Center, Wuhan 430071, Hubei, China. Electronic address: yuanhuan_xiong@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: He
authors.affiliation: Graduate School of Nanchang University, Nanchang 330006, Jiangxi, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Fei
mesh_terms: D000328:Adult; D060908:CTLA-4 Antigen / Q000235:genetics*; D063646:Carcinogenesis; D002277:Carcinoma / Q000235:genetics*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation; D008875:Middle Aged; D011110:Polymorphism, Genetic; D002583:Uterine Cervical Neoplasms / Q000235:genetics*
chemical_list: D060908:CTLA-4 Antigen; D016207:Cytokines
keywords: CTLA-4; Cervical cancer; Gene polymorphism