Healthy Lifestyle Modifications May Lower Risk of Genetically Induced Gout

A healthy lifestyle was associated with a lower risk of gout, mitigating risk related to genetic factors by almost a third, according to a study published in BMC Medicine.1

“Risk genes linked to the development of gout have been identified, and lifestyle factors are related to gout risk. It remains unclear whether healthy lifestyle factors can mitigate the genetic risk of gout,” investigators stated. “We aimed to explore whether and to what extent a healthy lifestyle can mitigate the risk of gout related to genetic factors.”

A total of 416,481 healthy controls (ages 37-74) were identified at baseline within the UK Biobank database, which recruited more than 500,000 participants. Information including sex, education, body mass index (BMI), disease history, socioeconomic status, employment status, and age was collected. Polygenic risk for developing gout was analyzed and categorized as low, middle, and high. Healthy lifestyle factors were listed as no or moderate alcohol consumption, regular physical activity, no smoking, and a healthy diet. Participants were placed into 3 categories: unfavorable (0 or 1), intermediate (2), and favorable (3 or 4).

Over the following 12.1 years, 6206 participants developed gout. Those who ultimately received a gout diagnosis were more likely to older, male, physically inactive, smokers, excessive alcohol drinkers, had lower educational attainment and socioeconomic status, and had an unhealthy diet. The hazard ratios (HRs) and 95% confidence intervals (CIs) of gout was 1.44 (1.35-1.54) for the middle cohort and 1.77 (1.66-1.89) for the high genetic risk when compared with participants with low genetic risk.

HRs of gout were 0.63 (0.59-0.67) for participants with a favorable lifestyle and 0.79 (0.75-0.85) for those with an intermediate lifestyle, compared with unfavorable habits. Gout related to a favorable lifestyle was 0.64 for low those with low genetic risk, 0.65 for those with middle genetic risk, and 0.62 for those with high genetic risk. A significant additive interaction was reported between participants with an unfavorable lifestyle and a high genetic risk for developing gout.

In terms of joint analysis, when compared with participants with a low genetic predisposition and a favorable lifestyle, the HRs of gout were 2.39 (2.12-2.70)/3.12 (2.79-3.52) for those with middle or high genetic predispositions coupled with unfavorable lifestyle choices, and 1.53 (1.35-1.74)/1.98 (1.74-2.24) for patients with middle and high genetic predisposition and favorable lifestyle profiles, respectively.

The large sample study coupled with the long follow-up period strengthened the study, in addition to the standardized measures of data collection and comprehensive diagnoses. However, any changes in lifestyle factors after baseline were not evaluated. Further, gout diagnosis was determined using medical records, which opens up the possibility that well-controlled gout or patients with minor flares may not have been recorded in hospitalization records, resulting in underestimation. Generalizability may be hindered because most patients were of White British descent and those who volunteered for the UK Biobank tended to be more health-conscious than those who did not participate, adding to underestimation of gout. While sources of bias were accounted for, confounding factors and reverse causation may remain.

“We found that genetic predisposition and unhealthy lifestyle factors were associated with increased risk of gout. However, a healthy lifestyle may attenuate the risk of gout related to genetic factors,” investigators concluded. “Our findings highlight the importance of maintaining a healthy lifestyle for the prevention of gout in people with a genetic predisposition.”

Reference:

Zhang Y, Yang R, Dove A, et al. Healthy lifestyle counteracts the risk effect of genetic factors on incident gout: a large population-based longitudinal study. BMC Med. 2022;20(1):138. Published 2022 Apr 29. doi:10.1186/s12916-022-02341-0