Past, Present and Future: Investigations into the history and possible causes of genetic predisposition to metabolic disorders in Pacific populations

Abstract

Many indigenous Pacific populations have been observed to have a high prevalence of Type 2 Diabetes and Gout. While lifestyle factors are likely to contribute, there is evidence to suggest that there is a hereditary contribution to these diseases. A number of genetic loci which confer risk have been identified – notably, polymorphisms in the genes SLC2A9 (rs16890979, rs5028843 and rs11942223) and ABCG2 (rs2231143) have been found to have statistically significant associations with Gout in Pacific Island and Maori populations in New Zealand.

Gout has been found to leave a bony signature in sufferers of the disease. Such lesions have been found in archaeological human remains from a number of Pacific Islands. The development of ancient DNA technologies provides a unique opportunity to explore the antiquity of genetic variants which have been found to contribute to gout in modern populations. Thus, this thesis aims to explore the feasibility of using ancient DNA to investigate genetic diseases in the past, and whether it can be used to determine the presence of polymorphisms predisposing to gout in these past populations. Samples excavated from archaeological sites at Wairau Bar, New Zealand and Atafu, Tokelau were used for this task. Consideration of human history in the Pacific, especially past population movements and entanglements, as well as selective pressures such as the introduction of diseases and adverse environmental conditions, contribute to understanding how these genetic variants may have become conflated in Pacific populations.