LAUSR

Urolithiasis is one of the rapidly increasing diseases in developed countries. It has been reported that urolithiasis is related with lifestyles, diet, obesity, climate and chronic diseases including hyperuricemia, diabetes mellitus, metabolic syndrome, chronic kidney disease et cetera. Among them, hyperuricemia is the leading cause of urolithiasis. ATP–binding cassette subfamily G member 2 (ABCG2), urate transporter, excretes uric acid in the kidney and the intestinal tract and ABCG2 dysfunction increases a risk of hyperuricemia. In this study, we investigated the estimated ABCG2 function by common two dysfunctional variants, Q126X (rs72552713) and Q141K (rs2231142), in patients with urolithiasis, and we evaluated the relation between urolithiasis and ABCG2 dysfunction. One hundred and ninety-seven urolithiasis patients without gout (150 males and 47 females) were enrolled. Q126X totally abolishes ABCG2 function, while Q141K reduces its function by about 50%. Since these two SNPs do not link each other and two SNPs do not exist on same chromosome, these two are regarded as independent risks. Namely, based on the genotype of Q126X and Q141K, it can be divided into three categories: a full functional group, a 75% functional group and a ≦50% functional group. Serum uric acid levels and amount of urinary uric acid were measured. Renal uric acid handling of the patients was classified into renal uric acid underexcretion type or renal uric acid overload type based on uric acid clearance and amount of urinary uric acid. Stone composition was analysed, if it had been possible. ABCG2 function of the patients was evaluated as follows: 82 patients, ABCG2 full function (41.6%); 78 patients, 75% function (39.6%); 37 patients, ≦50% function (18.8%). 155 patients were classified into renal uric acid underexcretion type, 13 patients were classified into renal uric acid overload type and 2 patients were classified into normal type (27 patients have not had 24-hour urine biochemical test). Stone composition analysis was performed for 136 patients; calcium oxalate stone was identified in 107 patients and uric acid stone in 29 patients. In this study, 58.4 % of the patients with urolithiasis had some ABCG2 dysfunction as against 49.8 % of the healthy individuals previously reported (p=0.0246). In addition, the ratio of subjects with urolithiasis having 50% or less of ABCG2 function was higher than healthy individuals significantly (OR=1.773, p=0.007). The high ratio of ABCG2 dysfunctional patients with urolithiasis suggested that ABCG2 dysfunction is a risk factor for urolithiasis. In the patients with urolithiasis, renal uric acid underexcretion type accounted for about 90% of the patients. This means that this type accelerated urolithiasis as well as hyperuricosuria. ABCG2 dysfunction and renal uric acid underexcretion type were suggested to be a risk factor for urolithiasis.