Polymorphic Elements of the Human IL-6 Gene in Gastric Cancer

Jordanides, Niove E (2001) Polymorphic Elements of the Human IL-6 Gene in Gastric Cancer. MSc(R) thesis, University of Glasgow.

Abstract

There has been much interest focusing on the contribution of cytokines to the genetic variation known to occur between the immune responses of different individuals. Interleukin-6 (IL-6), originally defined as a B cell growth factor, was rapidly identified as under-pinning the induction of the acute-phase response and being heavily involved in inflammatory responses generally. More recently, the role of IL-6 in human malignancy has become a topic of interest. The aim of this study was to examine four polymorphic elements, three in the promoter 5'region and one VNTR in the 3'region and define the relationships of these alleles in a West of Scotland control population. The relationships were then observed in two malignant cohorts; patients diagnosed with Gastric carcinoma and patients diagnosed with Barrett's Oesophagus, to determine possible disease related associations. Investigation of an African American cohort and subsequent rheumatoid individuals also provided a comparison in a different ethnic group and the associations of the polymorphic elements in an autoimmune disease. Digestion of amplified DNA determined the polymorphisms in the 5' promoter region and PAGE separation resolved the minisatellite alleles at the 3' VNTR. The data revealed that strong significant associations between the alleles form three prominent 5' promoter haplotype families and four dominant extended haplotypes, which include the 3'VNTR in the West-of-Scotland population. In the gastric carcinoma cohort the 4 polymorphisms were similarly distributed to the control population and did not prove to be genetic markers relating to this disease. Similarly no statistical significance was detected with the Barrett's Oesophagus cohort. However, the presence of H.pylori in the malignant cohorts proved to be of significant importance in the distribution the 5' haplotype families. The haplotype IL6.01 was significantly more prominent in H.Pylori positive patients of the gastric cohort, where as the haplotype IL6.02 was more prominent in the Barrett's Oesophagus patients. In the African American population, no statistical difference was detected between the control cohort and the Rheumatoid arthritis patients. The results reported here demonstrate that markers cannot necessarily be considered independent of one another across human cytokine genes. Additionally, where markers fall in, or close to, functional elements such as transcription factor binding sites, it should be remembered that other polymorphic elements might be contributing to the observed effect.

• Item Type: Thesis (MSc(R))
• Qualification Level: Masters
• Additional Information: Adviser: Joyce Eskdale
• Keywords: Genetics
• Date of Award: 2001
• Depositing User: Enlighten Team
• Unique ID: glathesis:2001-75721
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 19 Nov 2019 18:31
• Last Modified: 19 Nov 2019 18:31
• URI: https://theses.gla.ac.uk/id/eprint/75721