Effect of genetic polymorphisms on development of gout.

Objective: To validate the association between genetic polymorphisms and gout in Japanese patients, and to investigate the cumulative effects of multiple genetic factors on the development of gout.

Methods: Subjects were 153 Japanese male patients with gout and 532 male controls. The genotypes of 11 polymorphisms in the 10 genes that have been indicated to be associated with serum uric acid levels or gout were determined. The cumulative effects of the genetic polymorphisms were investigated using a weighted genotype risk score (wGRS) based on the number of risk alleles and the OR for gout. A model to discriminate between patients with gout and controls was constructed by incorporating the wGRS and clinical factors. C statistics method was applied to evaluate the capability of the model to discriminate gout patients from controls.

Results: Seven polymorphisms were shown to be associated with gout. The mean wGRS was significantly higher in patients with gout (15.2 ± 2.01) compared to controls (13.4 ± 2.10; p < 0.0001). The C statistic for the model using genetic information alone was 0.72, while the C statistic was 0.81 for the full model that incorporated all genetic and clinical factors.

Conclusion: Accumulation of multiple genetic factors is associated with the development of gout. A prediction model for gout that incorporates genetic and clinical factors may be useful for identifying individuals who are at risk of gout.