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Genetic variations in cytotoxic T-lymphocyte antigen-4 and susceptibility to cervical cancer.
MedLine Citation:
PMID:  24201079     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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. A case-control study was conducted in Han women living in Southeast China to evaluate the potential effects of CTLA-4 gene polymorphisms on susceptibility to cervical cancer. We genotyped polymorphisms in CTLA-4 (-318T/C, CT60 G/A, +49G/A, -658T/C, and -1661G/A) and calculated odds ratios for the genotype and allele distributions between patients and controls, in order to assess the association between CTLA-4 genotypes and cancer risk. 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 -318T allele and CT60G allele carriers were significantly higher in patients than in controls (p<0.05). No significant differences were found in the genotype and allele frequencies in -658T/C, and -1661G/A between patients and healthy 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 -318T/C and CT60 G/A single nucleotide polymorphisms were associated with the severity of cervical cancer. These results indicate that CTLA-4 -318T/C and CT60 G/A can affect cervical cancer susceptibility by altering the immune status of an individual.
Authors:
Yuan-Huan Xiong; Li He; Jing Fei
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-11-4
Journal Detail:
Title:  International immunopharmacology     Volume:  -     ISSN:  1878-1705     ISO Abbreviation:  Int. Immunopharmacol.     Publication Date:  2013 Nov 
Date Detail:
Created Date:  2013-11-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100965259     Medline TA:  Int Immunopharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013.
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.
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