RESUMO
Prolactin has been shown to be active as an immunomodulatory hormone and is therefore of potential importance in disease progression and development. Any polymorphism in the gene and regulatory sequences may prove useful for disease association studies. A Bg/II polymorphism has been previously detected within the prolactin gene region. We have mapped this polymorphism to intron C and detected the base mutation that causes it. We have also developed a PCR-RFLP method to genotype individuals.
Assuntos
Proteínas de Bactérias , Polimorfismo Genético , Prolactina/genética , Alelos , Sequência de Bases , Cromossomos Humanos Par 6 , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Genótipo , Humanos , Íntrons , Modelos Genéticos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de RestriçãoRESUMO
High-risk human papillomavirus (HPV) infection plays an important role in cervical intra-epithelial neoplasia (CIN), but HPV infection alone is not sufficient for progression to cervical cancer. Several lines of evidence suggest that cellular immune surveillance is important in the control of HPV infection and the development of CIN. The presentation to T cells of target viral peptides in the context of HLA molecules is influenced by the genetic polymorphisms of both HPV and HLA and thereby influences the host immune response and clinical outcome of HPV infection. HLA class I and II polymorphism in susceptibility for HPV 16 infection, development and progression of CIN was analyzed in a group of 118 patients participating in a prospective study of women with initial abnormal cytology. Patients were stratified according to HPV status and course of the disease. HLA-B*44 frequency was increased in the small group of patients with a lesion that showed clinical progression during follow-up [OR = 9.0 (4.6-17.5), p = 0.007]. HLA-DRB1*07 frequency was increased among HPV 16-positive patients compared with patients who were negative for all HPV types [OR = 5.9 (3.0-11.3), p = 0.02]. Our results are consistent with the immunogenetic factors associated with disease progression being different from those associated with susceptibility to HPV 16 infection. Sequencing of the HPV 16 E6 and E7 open reading frames of a subset of these patients (n = 40) showed the frequency of HPV 16 variants to be similar to other studies. However, there was no significant correlation between variant incidence and disease progression or viral persistence and no significant correlation with any HLA allele. It appears that multiple HLA types can influence HPV 16-associated cervical dysplasia but the role of HPV 16 variants in disease progression and susceptibility in relation to HLA polymorphism remains unclear.
Assuntos
Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe I/genética , Proteínas Oncogênicas Virais/genética , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Proteínas Repressoras , Infecções Tumorais por Vírus/complicações , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/virologia , Adulto , Alelos , Progressão da Doença , Feminino , Variação Genética , Genótipo , Humanos , Pessoa de Meia-Idade , Fases de Leitura Aberta , Proteínas E7 de Papillomavirus , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , Polimorfismo Genético , Estudos Prospectivos , Infecções Tumorais por Vírus/genética , Infecções Tumorais por Vírus/virologia , Neoplasias do Colo do Útero/patologia , Displasia do Colo do Útero/patologiaRESUMO
No HLA allele or specificity was significantly different in frequency between a group of 150 cervical cancer patients from north-west England and controls (corrected P values). HLA-DRB1*1501/DQB1*0602 was non-significantly increased, particularly among patients with HPV16-positive tumours. HLA-B7-positive patients had a significantly poorer clinical outcome than HLA-B7-negative patients. A significant component of the genotypic effect is down-regulation of HLA-B7 expression by the tumour cells.
