Why are Polynesians more susceptible to gout?

Polynesian Susceptibility to Gout: Genetic and Environmental Factors

Polynesians have significantly higher rates of gout due to a genetic defect in renal urate handling, which is compounded by dietary and lifestyle factors that have emerged with urbanization and migration to Western environments. 1

Genetic Factors

• Polynesian populations have an inherent genetic defect in renal urate handling, characterized by reduced fractional uric acid clearance (FEur), leading to hyperuricemia 1
• Studies show that Polynesian women have a FEur of 6.7% compared to 12.8% in healthy UK women, indicating a significant reduction in the kidney's ability to clear uric acid 1
• Even normouricemic Polynesians demonstrate lower FEur (9.7%) than their European counterparts, suggesting this is a population-wide genetic characteristic 1
• The genetic defect appears more pronounced in Polynesian men, who show even lower FEur values (3.9-4.9%) than Polynesian women, explaining the higher prevalence of gout in males 1

Epidemiological Evidence

• French Polynesia has an extremely high prevalence of gout at 14.5% of the adult population, with 25.5% of males and 3.5% of females affected 2
• Hyperuricemia affects 71.6% of the French Polynesian adult population, creating a large at-risk population 2
• Migration studies of Tokelauans show that those who migrated to urban New Zealand had 9 times higher risk of developing gout compared to non-migrants who remained in their traditional environment 3
• Māori individuals with diabetes have significantly worse health outcomes than other Pacific Islanders despite shared Polynesian genetic ancestry, suggesting complex interactions between genetics and environment 4

Risk Factors and Associations

• In multivariable analysis, risk factors for gout in Polynesians include: age, male sex, elevated serum urate, type 2 diabetes, obesity (BMI >30 kg/m²), and increased visceral fat 2
• Polynesian populations show high rates of obesity which increases with age, contributing to hyperuricemia and gout risk 1
• High purine intake is common in traditional and modern Polynesian diets, further contributing to urate burden 1
• Unlike in other populations, alcohol and hypertension were not significant contributors to hyperuricemia in some Polynesian studies 1

Pharmacogenetic Considerations

• CYP2C9 poor metabolizer alleles (relevant for metabolism of some urate-lowering therapies like benzbromarone) are significantly less common in Polynesians (CYP2C92: 3.1%, CYP2C93: 1.6%) compared to Caucasians (CYP2C92: 13.5%, CYP2C93: 5.5%) 5
• Western Polynesians (Samoans, Tongans) have even lower frequencies of these alleles than Eastern Polynesians (New Zealand and Cook Island Māori) 5
• This pharmacogenetic difference may influence treatment response and safety profiles of certain medications used for gout in Polynesian populations 5

Environmental and Lifestyle Factors

• Migration from traditional to urban environments significantly increases gout risk, as demonstrated by the Tokelau Island migrant study 3
• Dietary changes with urbanization, including increased consumption of meat, seafood, and fructose-rich foods, contribute to hyperuricemia 6
• Socioeconomic factors may influence healthcare access and treatment patterns in Polynesian populations 4

Management Implications

• Preventive strategies should focus on modifiable risk factors including body mass, diet patterns, and alcohol consumption 3
• Dietary recommendations for gout patients should include limiting alcohol intake, weight loss if overweight/obese, and reducing fructose intake 4
• Every person with gout should receive lifestyle advice including weight management and avoidance of alcohol (especially beer and spirits), sugar-sweetened drinks, and excessive intake of meat and seafood 4
• Low-fat dairy products should be encouraged as they may have protective effects against hyperuricemia 4

Understanding the unique genetic predisposition of Polynesian populations to gout is essential for developing targeted prevention and treatment strategies that address both the inherent renal urate handling defect and the modifiable environmental factors that contribute to this significant health disparity.