Gout: A Review of Nonmodifiable and Modifiable Risk Factors

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Key points

  • The prevalence of gout and hyperuricemia increases with age; women tend to be affected by gout at an older age than their male counterparts.

  • 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.

  • Alcohol, purines from meat and seafood, and fructose- or sugar-sweetened beverages have been associated with increased risk of incident gout, whereas

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

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References (146)

  • C. Wallace et al.

    Genome-wide association study identifies genes for biomarkers of cardiovascular disease: serum urate and dyslipidemia

    Am J Hum Genet

    (2008)
  • A. Mobasheri et al.

    Human articular chondrocytes express three facilitative glucose transporter isoforms: GLUT1, GLUT3 and GLUT9

    Cell Biol Int

    (2002)
  • A. Dehghan et al.

    Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study

    Lancet

    (2008)
  • M.J. Maclachlan et al.

    Effect of food, fast and alcohol on serum uric acid and acute attacks of gout

    Am J Med

    (1967)
  • T. Yamamoto et al.

    Effect of beer on the plasma concentrations of uridine and purine bases

    Metabolism

    (2002)
  • H.K. Choi et al.

    Alcohol intake and risk of incident gout in men: a prospective study

    Lancet

    (2004)
  • S.R. Dalvi et al.

    Saturnine gout, redux: a review

    Am J Med

    (2013)
  • R. Villegas et al.

    Purine-rich foods, protein intake, and the prevalence of hyperuricemia: the Shanghai Men's Health Study

    Nutr Metab Cardiovasc Dis

    (2012)
  • K.H. Yu et al.

    Dietary factors associated with hyperuricemia in adults

    Semin Arthritis Rheum

    (2008)
  • I.H. Fox et al.

    Studies on the mechanism of fructose-induced hyperuricemia in man

    Metabolism

    (1972)
  • K.O. Raivio et al.

    Stimulation of human purine synthesis de novo by fructose infusion

    Metabolism

    (1975)
  • D.D. Wang et al.

    The effects of fructose intake on serum uric acid vary among controlled dietary trials

    J Nutr

    (2012)
  • D.R. Garrel et al.

    Milk- and soy-protein ingestion: acute effect on serum uric acid concentration

    Am J Clin Nutr

    (1991)
  • M.S. Lipkowitz

    Regulation of uric acid excretion by the kidney

    Curr Rheumatol Rep

    (2012)
  • V. Bhole et al.

    Epidemiology of gout in women: fifty-two-year followup of a prospective cohort

    Arthritis Rheum

    (2010)
  • Y. Zhu et al.

    Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008

    Arthritis Rheum

    (2011)
  • J.A. Singh et al.

    Risk factors for gout and prevention: a systematic review of the literature

    Curr Opin Rheumatol

    (2011)
  • K.L. Wallace et al.

    Increasing prevalence of gout and hyperuricemia over 10 years among older adults in a managed care population

    J Rheumatol

    (2004)
  • J.W. Maynard et al.

    Racial differences in gout incidence in a population-based cohort: Atherosclerosis Risk in Communities Study

    Am J Epidemiol

    (2014)
  • A.M. Reginato et al.

    The genetics of hyperuricaemia and gout

    Nat Rev Rheumatol

    (2012)
  • H.K. Choi et al.

    Pathogenesis of gout

    Ann Intern Med

    (2005)
  • M.A. Öztürk et al.

    Demographic and clinical features of gout patients in Turkey: a multicenter study

    Rheumatol Int

    (2013)
  • J.H. Chen et al.

    Gender-specific risk factors for incident gout: a prospective cohort study

    Clin Rheumatol

    (2012)
  • J.G. Puig et al.

    Female gout. Clinical spectrum and uric acid metabolism

    Arch Intern Med

    (1991)
  • A.E. Hak et al.

    Menopause, postmenopausal hormone use and serum uric acid levels in US women–the Third National Health and Nutrition Examination Survey

    Arthritis Res Ther

    (2008)
  • A.E. Hak et al.

    Menopause, postmenopausal hormone use and risk of incident gout

    Ann Rheum Dis

    (2010)
  • Y. Takiue et al.

    The effect of female hormones upon urate transport systems in the mouse kidney

    Nucleosides Nucleotides Nucleic Acids

    (2011)
  • H.K. Choi et al.

    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)

    (2008)
  • J. Fang et al.

    Serum uric acid and cardiovascular mortality the NHANES I epidemiologic follow-up study, 1971-1992. National Health and Nutrition Examination Survey

    JAMA

    (2000)
  • K.G. Saag et al.

    Epidemiology, risk factors, and lifestyle modifications for gout

    Arthritis Res Ther

    (2006)
  • M. Kuzuya et al.

    Effect of aging on serum uric acid levels: longitudinal changes in a large Japanese population group

    J Gerontol A Biol Sci Med Sci

    (2002)
  • M.C. Hochberg et al.

    Racial differences in the incidence of gout. The role of hypertension

    Arthritis Rheum

    (1995)
  • A.L. Gaffo et al.

    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

    (2012)
  • P. Klemp et al.

    Gout is on the increase in New Zealand

    Ann Rheum Dis

    (1997)
  • J.A. Singh

    Racial and gender disparities among patients with gout

    Curr Rheumatol Rep

    (2013)
  • D. Winnard et al.

    National prevalence of gout derived from administrative health data in Aotearoa New Zealand

    Rheumatology (Oxford)

    (2012)
  • L.K. Stamp et al.

    Hyperuricaemia and gout in New Zealand rural and urban Maori and non-Maori communities

    Intern Med J

    (2013)
  • A.J. Portis et al.

    High prevalence of gouty arthritis among the Hmong population in Minnesota

    Arthritis Care Res (Hoboken)

    (2010)
  • S. Wahedduddin et al.

    Gout in the Hmong in the United States

    J Clin Rheumatol

    (2010)
  • P. Prasad et al.

    Filipino gout: a review

    Arthritis Care Res (Hoboken)

    (2014)
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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.

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