Published: Nov 23, 2013 | Updated: Nov 25, 2013

Full Story:  http://www.medpagetoday.com/Rheumatology/GeneralRheumatology/43087

By Nancy Walsh, Staff Writer, MedPage Today

Gout does cluster within families, with increased risks being seen for individuals with affected close relatives, a cross-sectional study confirmed.

Among individuals who have affected first-degree relatives — parents, offspring, or siblings — the relative risk of gout was 1.91 (95% CI 1.90-1.93) for men and 1.97 (95% CI 1.94-1.99) for women, according to Chang-Fu Kuo, PhD, of the University of Nottingham in England, and colleagues.

And for those with affected second-degree relatives — grandparents, uncles and aunts, and nieces and nephews — men had a relative risk of 1.27 (95% CI 1.23-1.31) and women had a relative risk of 1.40 (95% CI 1.35-1.46), the researchers reported online in Annals of the Rheumatic Diseases.

Gout is recognized as having a heritable component, but many environmental influences such as obesity, hypertension, diuretic use, and diets high in purines and alcohol also are considered important.

“Currently, the balance between genetic and environmental contributions is still unclear,” observed Kuo and colleagues.

Previous studies have suggested that there may be a genetic susceptibility to hyperuricemia, although the association with clinical gout has been less clear, with a U.S. twin study finding no heritability for clinical disease.

To clarify the issue, the researchers conducted a nationwide study in Taiwan, where there is a national health insurance database and prevalence of gout is strikingly high.

The study population included 11,360,576 men and 11,283,172 women enrolled in the database in 2004, of whom 802,765 men and 242,294 women had been diagnosed with gout.

The overall prevalence was 4.62%, while the prevalence for men was 7.07% compared with 2.15% for women.

For those with an affected first-degree relative, the prevalence was 13.37% (95% CI 13.35-13.39) among men and 4.16% (95% CI 4.15-4.18) among women, and for those with an affected second-degree relative, the prevalences were 10.05% (95% CI 10.03-10.06) and 3.01% (95% CI 3-3.02), respectively.

Risks rose additionally when more than one relative had a gout diagnosis. When there were two affected first-degree relatives, the risk was 3.22 (95% CI 3.15-3.29), and when there were three or more, the risk was 4.96 (95% CI 4.64-5.30).

“Biological relatives tend to share similar environmental and lifestyle risk factors in addition to genes; both contribute to familial aggregation. Therefore, we examined the risk associated with having a spouse who has gout on the assumption that any increased risk from this predominantly reflects predisposition from environmental and lifestyle factors,” the researchers wrote.

Men with an affected wife had a relative risk of 1.66 (95% CI 1.65-1.68), while women with affected husbands had a relative risk of 1.65 (95% CI 1.64-1.67).

“To separate the influences of genes and environment, we calculated heritability and familial transmission,” they explained. Heritability among men was 35.1% (95% CI 34.1-36) while familial transmission was 63.2% (95% CI 61.8-64.7).

In women, heritability was 17% (95% CI 15-19) and familial transmission was 35.5% (95% CI 33.1-37.8).

“Therefore, although not the sole explanation for familial aggregation, genetic factors in addition to environmental influences do contribute to the development of gout,” they stated.

Strengths of the study included the large population and minimal selection bias, but it was limited to Taiwan and the findings may not be widely generalizable. In addition, there may have been confounding factors not measured in the national database.

Further studies in other populations should be undertaken to validate these results, they concluded.