Experiencing Gout in New Zealand: The Genetic and Dietary Influences of a Complex Disease.
Flynn, Tanya J.
Gout is a complex human disease characterised by attacks of extreme, debilitating pain followed by asymptomatic periods of indeterminate length. Within New Zealand gout is a serious health issue. Approximately 7% of New Zealand Māori and Pacific Island people are affected by gout, whilst 3% of New Zealand Europeans are affected. It has become so prevalent in this country that South Auckland has been labelled the “gout capital of the world.” This thesis aims to find reasons for this high disease prevalence by searching for genetic and dietary influences of serum urate levels and gout risk in quantitative studies, whilst also including a qualitative study of the understandings of disease held by New Zealand gout patients. Gout develops as an inflammatory response to monosodium urate crystals within the joints. These crystals are able to form when an individual’s serum urate (the anionic form of uric acid) reaches an unusually high level within the blood (hyperuricaemia). Crystals begin to build-up within the joints (most often the big toe) and can result in a gout attack. Urate levels are maintained through a delicate balance between hepatic production and (primarily) renal excretion. Multiple proteins are involved in maintaining this balance. Genetic variants in the genes encoding these proteins can disrupt this balance, resulting in a greater genetic predisposition to developing gout. Polynesian and European ancestry-specific genetic effects were identified for common variants within or near two uric acid transporter genes (SLC22A11 (OAT4) and SLC22A12 (URAT1)). Rare variants within these same two genes were also identified and a greater prevalence of non-synonymous mutations that result in protection from hyperuricaemia was found in European individuals compared to Polynesian. These results indicate SLC22A11 (OAT4) and SLC22A12 (URAT1) may significantly contribute to the large difference in gout prevalence between Māori and Pacific Island men compared to New Zealand European men. A genetic predisposition is not the only possible cause of gout. Certain foods, drinks, and activities (called triggers) can influence serum urate levels and/or initiate gout attacks. These triggers are not strictly considered to be causes of gout, but rather influence when a person who is already predisposed to gout develops the disease. However, ethnographic interviews with gout sufferers revealed that this distinction is not often emphasised and patients had a greater focus on the dietary and lifestyle factors involved in gout risk over the genetic or biochemical aspects. In response to this observation a series of analyses were conducted to assess the contributions individual food items have in the risk of gout, acute gout attack onset, and serum urate levels. Almost two hundred different food items were listed as gout trigger foods by New Zealand gout patients, with over 70% of gout patients naming at least one personal trigger food. New Zealand Māori and Pacific Island individuals were twice as likely to list any trigger food than New Zealand European individuals. Of all the food items listed as triggers, those that were most commonly mentioned (seafood, alcohol, and tomatoes) were also significantly associated with raised serum urate levels, and tomatoes (a novel urate-influencing food) interacted with the uric acid transporter gene SLC22A12 (URAT1) to further influence serum urate. Other foods that were rarely mentioned as gout triggers (brown bread, peanuts, margarine, and eggs) had novel associations with lowered serum urate levels. Dietary factors explained 3.1% of variation in urate levels, but an estimate of each individual’s overall dietary habits only explained 0.1% of the variation in serum urate levels. Both measures explained less variation in serum urate than genetic factors (5% to 7%). The results within this thesis show that both genes and diet significantly contribute toward the determination of an individual’s serum urate levels and risk of gout. This work highlights the importance of integrating patient and researcher understandings of disease to open up new or unthought-of avenues of investigation, focus research aims, and provide support for previously disregarded patient claims. It is a step towards an improved understanding of the experience of gout in New Zealand and the genetic and dietary influences of this complex disease.
Advisor: Merriman, Tony R.; Fitzgerald, Ruth P.
Degree Name: Doctor of Philosophy
Degree Discipline: Biochemistry Department (Genetics Division)
Publisher: University of Otago
Keywords: Gout; Genetics; New Zealand; Diet; SLC22A12; SLC22A11; Tomatoes; DWAS; Experiences; Uric Acid; Urate; Maori; Pacific Island; Polynesian
Research Type: Thesis