Determination of cytokine and mannose binding lectine(MBL) gene polymorphisms in anogenital human papillomavirus(HPV) infections

Thesis Type: Doctorate

Institution Of The Thesis: Uludağ Üniversitesi, Turkey

Approval Date: 2012

Thesis Language: Turkish




Human papillomaviruses (HPV) are naked double stranded DNA viruses belonging to the family of Papillomaviruses. They are classified into more than 100 types. Anogenital HPV infections (Condyloma acuminatum,CA) are being increasingly recognized as important infectious agents. The balance between type Th1 and Th2 cytokines in patients with CA is thought to modulate antiviral immunity. Several genes encoding different cytokines may play crucial roles in host susceptibility to HPV infections, since cytokine production capacity varies among individuals and depends on cytokine gene polymorphisms. Mannose?binding lectin (MBL) is a serum lectin that mediates complement activation and it is a member of innate immune system. MBL genes are also related to the amount of the MBL produced. MBL gene polymorphisms are considered to be associated with several infectious diseases.In this study, we investigated the association between cytokines and MBL gene polymorphisms with anogenital HPV infections.Fourty patients with CA and 40 healthy controls were enrolled in this study. These patients had no responded to at least a therapy modality (electrosurgery, cryotherapy, topical imiquimod, chemical ablation methods, etc.) and all patients had recurrent lesions. Polymorphism of cytokine (Th1 cytokines; TNF-? and IFN-?, Th2 cytokine; IL-6, T regulatory/supressor cytokines; IL-10 and TGF-ß) genes studies were performed using sequence-specific primers Polmerase chain reaction (PCR-SSP) method and MBL genotyping were studied by PCR-Restriction Fragment Lenght Polymorphism (RFLP) method. With the aid of agglomerative hierarchical cluster analysis, we categorized subjects into 2 major cluster, which were found to have significantly different distributions of IL-6 and MBL genotypes. Frequencies of IL-6 (-174) G/G (p<0.001) and MBL (codon 54) AA (p<0.001) polymorphisms were significantly greater in the cluster 1 (cluster formed by the majority of patients with CA). In contrast, significantly lower frequencies of the IL-6 G/C (p=0.046) genotype and MBL (codon 54) AB (p<0.001) genotype were observed in cluster 1 compared with cluster 2 (cluster formed by the majority of healthy controls).These results suggest that the IL-6 G/G and MBL AA gene polymorphisms are potential risk factors, and that the IL-6 G/C and MBL AB polymorphisms are a protective factor, for occurrence and recurrence of anogenital HPV infections in this study group. The incidence of anogenital HPV infections in Turkey is growing day by day and larger studies are therefore necessary to investigate the role the gene polymorphisms involved in the pathogenesis of anogenital HPV infections.