Effects of ABCG2 dysfunction on hyperuricemia progression in premenopausal and postmenopausal women

Abstract Serum uric acid (SUA) levels are influenced by environmental and genetic factors, such as sex and ABCG2 variants. Their poorlyunderstood links to menstrual status prompted us to conduct this study to evaluate the effects of menstrual status-related ABCG2 function, detectable from the presence of its dysfunctional variants, on SUA levels. Recruited for the present study were 9244 Japanese individuals, comprising 4466 women and 4778 men. We evaluated the effect size on SUA and population attributable fractions (PAFs) for hyperuricemia progression based on factors, including ABCG2 function, BMI, alcohol consumption, age, and menstrual status (in women). The results, from the viewpoint of SUA increase, showed a 25% ABCG2 dysfunction to be equivalent to the effects of a 1.67 kg/m 2 increase in BMI, alcohol consumption of 154.2 g/week, an 18.6-year increase in age, and, in women, 42.7% due to menopause. In the tested female sample, the PAF for hyperuricemia due to ABCG2 dysfunction (32.8%) exceeded those for overweight/obesity (19.5%) and aging (28.7%). Menopausal status exhibited the highest PAF at 63.0%. In premenopausal individuals, the PAF for ABCG2 dysfunction was 45.8%, much higher than that after menopause (29.6%). Although premenopausal women generally had a lower prevalence of hyperuricemia than postmenopausal individuals, those with dysfunctional variants of ABCG2 tended to show a higher SUA increase and PAFs in premenopausal than in postmenopausal women. These results indicate that genetic testing might be helpful in preventing and treating hyperuricemia, particularly for those with higher SUA before menopause, in both individuals and in populations as a whole.