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The prevalence of gout and hyperuricemia increases with age; women tend to be affected by gout at an older age than their male counterparts.
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Genome-wide association studies (GWAS) have identified several genetic polymorphisms, mainly affecting renal urate excretion, which alter serum uric acid levels and subsequently the risk of developing gout.
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Alcohol, purines from meat and seafood, and fructose- or sugar-sweetened beverages have been associated with increased risk of incident gout, whereas
Gout: A Review of Nonmodifiable and Modifiable Risk Factors
Section snippets
Key points
Gender
In the population under 65 years of age, men have a 4-fold higher prevalence of gout than do women; however, this male-to-female ratio reduces to 3:1 over 65 years.8 For women as for men, higher levels of uric acid confer an increase in risk of gout. Prospective cohort data suggest the incidence of gout in women increases with serum uric acid levels but at a lower rate of this increase, such that women with a uric acid level greater than 5 mg/dL have a significantly lower risk of gout than male
Heritability
In the early 1990s, Emmerson and colleagues34 sought to explain a genetic predisposition for gout through renal urate clearance. In studying 37 pairs of normouricemic twins, they found that monozygotic twins had more similar values of urate clearance and fractional excretion of urate than dizygotes. They calculated the heritability of renal urate clearance to be 60%, whereas the heritability of the fractional excretion of urate was 87%.34 Further investigation through segregation analysis on
Alcohol
Since antiquity, alcohol consumption has been linked to gout. More formal research from the 1960s demonstrated that alcohol administration caused decreased uric acid excretion and hyperuricemia.61 Ethanol ingestion increases serum lactate levels, which inhibit uric acid excretion at the renal tubule; however, this has not been confirmed in subsequent studies.62 In terms of the production theory, ethanol prompts ATP consumption, leading to purine degradation, yielding an increase in plasma
Other lifestyle factors
Few studies examined the role of physical activity and body weight on the risk of gout. A study of male runners found that men who ran over 4 km/d or faster than 4.0 m/s had a lower incidence of gout, although this was partially attributable to their leaner frames and BMI.113 In a prospective cohort of men, Choi and colleagues114 found that greater BMI correlated with increased age-adjusted RR of incident gout, BMI of 25 to 29.9 (RR 1.95; 95% CI, 1.44–2.65), BMI of 30 to 34.9 (RR 2.33; 95% CI,
Summary
There is robust evidence for nonmodifiable and modifiable risk factors and their contribution to incident gout. Although a patient’s individual risk likely represents a complex interplay between factors outside of their control, such as age, gender, race, and genetics, and modifiable factors, such as diet and lifestyle, patients at risk for hyperuricemia or gout should be educated on modifiable factors to reduce the risk. With the current knowledge in the literature, it is conceivable that a
References (146)
- et al.
Epidemiology of Gout
Rheum Dis Clin North Am
(2014) - et al.
Asymptomatic hyperuricemia. Risks and consequences in the Normative Aging Study
Am J Med
(1987) - et al.
A revised estimate of the burden of illness of gout
Curr Ther Res Clin Exp
(2013) - et al.
The genetic basis of gout
Rheum Dis Clin North Am
(2014) - et al.
Racial/ethnic and sex differences in the relationship between uric acid and metabolic syndrome in adolescents: an analysis of National Health and Nutrition Survey 1999-2006
Metabolism
(2012) Gout in Maoris
Semin Arthritis Rheum
(1975)- et al.
Genome-wide search for genes affecting serum uric acid levels: the Framingham Heart Study
Metabolism
(2005) - et al.
A high prevalence of renal hypouricemia caused by inactive SLC22A12 in Japanese
Kidney Int
(2004) - et al.
Plasma urate level is directly regulated by a voltage-driven urate efflux transporter URATv1 (SLC2A9) in humans
J Biol Chem
(2008) - et al.
Mutations in glucose transporter 9 gene SLC2A9 cause renal hypouricemia
Am J Hum Genet
(2008)
Genome-wide association study identifies genes for biomarkers of cardiovascular disease: serum urate and dyslipidemia
Am J Hum Genet
Human articular chondrocytes express three facilitative glucose transporter isoforms: GLUT1, GLUT3 and GLUT9
Cell Biol Int
Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study
Lancet
Effect of food, fast and alcohol on serum uric acid and acute attacks of gout
Am J Med
Effect of beer on the plasma concentrations of uridine and purine bases
Metabolism
Alcohol intake and risk of incident gout in men: a prospective study
Lancet
Saturnine gout, redux: a review
Am J Med
Purine-rich foods, protein intake, and the prevalence of hyperuricemia: the Shanghai Men's Health Study
Nutr Metab Cardiovasc Dis
Dietary factors associated with hyperuricemia in adults
Semin Arthritis Rheum
Studies on the mechanism of fructose-induced hyperuricemia in man
Metabolism
Stimulation of human purine synthesis de novo by fructose infusion
Metabolism
The effects of fructose intake on serum uric acid vary among controlled dietary trials
J Nutr
Milk- and soy-protein ingestion: acute effect on serum uric acid concentration
Am J Clin Nutr
Regulation of uric acid excretion by the kidney
Curr Rheumatol Rep
Epidemiology of gout in women: fifty-two-year followup of a prospective cohort
Arthritis Rheum
Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008
Arthritis Rheum
Risk factors for gout and prevention: a systematic review of the literature
Curr Opin Rheumatol
Increasing prevalence of gout and hyperuricemia over 10 years among older adults in a managed care population
J Rheumatol
Racial differences in gout incidence in a population-based cohort: Atherosclerosis Risk in Communities Study
Am J Epidemiol
The genetics of hyperuricaemia and gout
Nat Rev Rheumatol
Pathogenesis of gout
Ann Intern Med
Demographic and clinical features of gout patients in Turkey: a multicenter study
Rheumatol Int
Gender-specific risk factors for incident gout: a prospective cohort study
Clin Rheumatol
Female gout. Clinical spectrum and uric acid metabolism
Arch Intern Med
Menopause, postmenopausal hormone use and serum uric acid levels in US women–the Third National Health and Nutrition Examination Survey
Arthritis Res Ther
Menopause, postmenopausal hormone use and risk of incident gout
Ann Rheum Dis
The effect of female hormones upon urate transport systems in the mouse kidney
Nucleosides Nucleotides Nucleic Acids
Haemoglobin A1c, fasting glucose, serum C-peptide and insulin resistance in relation to serum uric acid levels–the Third National Health and Nutrition Examination Survey
Rheumatology (Oxford)
Serum uric acid and cardiovascular mortality the NHANES I epidemiologic follow-up study, 1971-1992. National Health and Nutrition Examination Survey
JAMA
Epidemiology, risk factors, and lifestyle modifications for gout
Arthritis Res Ther
Effect of aging on serum uric acid levels: longitudinal changes in a large Japanese population group
J Gerontol A Biol Sci Med Sci
Racial differences in the incidence of gout. The role of hypertension
Arthritis Rheum
Association between being African-American, serum urate levels and the risk of developing hyperuricemia: findings from the Coronary Artery Risk Development in Young Adults cohort
Arthritis Res Ther
Gout is on the increase in New Zealand
Ann Rheum Dis
Racial and gender disparities among patients with gout
Curr Rheumatol Rep
National prevalence of gout derived from administrative health data in Aotearoa New Zealand
Rheumatology (Oxford)
Hyperuricaemia and gout in New Zealand rural and urban Maori and non-Maori communities
Intern Med J
High prevalence of gouty arthritis among the Hmong population in Minnesota
Arthritis Care Res (Hoboken)
Gout in the Hmong in the United States
J Clin Rheumatol
Filipino gout: a review
Arthritis Care Res (Hoboken)
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Disclosures: S.C. Kim is supported by the National Institutes of Health grant K23 AR059677. She received a research grant from Pfizer.