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Background  Although  SLC22A12 258X  allele was found among those with hypouricemia, it was unknown that serum uric acid distribution among those with  SLC22A12 258X  allele. This study examined serum uric acid (SUA) distribution according to  SLC22A12  W258X genotype in a general Japanese population.    Methods  Subjects were 5,023 health checkup examinees (3,413 males and 1,610 females) aged 35 to 69 years with creatinine < 2.0 mg/dL, who were participants of a cohort study belonging to the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study).  SLC22A12  W258X was genotyped with a polymerase chain reaction with confronting two-pair primers.    Results  The genotype frequency was 4,793 for  WW , 225 for  WX , and 5 for  XX , which was in Hardy-Weinberg equilibrium (p = 0.164) with  X  allele 0.023 (95% confidence interval [0.021-0.027]). Mean (range) SUA was 6.2 (2.1-11.4) mg/dL for  WW , 3.9 (0.8-7.8) mg/dL for  WX , and 0.8 (0.7-0.9) mg/dL for  XX  among males, and 4.5 (1.9-8.9) mg/dL, 3.3 (2.0-6.5) mg/dL, and 0.60 (0.5-0.7) mg/dL among females, respectively. Six individuals with SUA less than 1.0 mg/dL included two males with  XX  genotype, one male with  WX  genotype, and three females with  XX  genotype. Subjects with  WX  genotype were 14 (77.8%) of 18 males with a SUA of 1.0-2.9 mg/dL, and 28 (34.6%) of 81 females with the same range of SUA. The corresponding values were 131 (25.1%) of 522 males and 37 (3.5%) of 1,073 females for SUA 3.0-4.9 mg/dL, and 8 (0.4%) of 2,069 males and 5 (1.1%) of 429 females for SUA 5.0-6.9 mg/dL. The  X  allele effect for SUA less than 3 mg/dL was significantly (p < 0.001) higher in males (OR = 102.5, [33.9-309.8]) than in females (OR = 25.6 [14.4-45.3]).    Conclusions  Although  SLC22A12  W258X was a determining genetic factor on SUA, SUA of those with  WX  genotype distributed widely from 0.8 mg/dL to 7.8 mg/dL. It indicated that other genetic traits and/or lifestyle affected SUA of those with  WX  genotype, as well as those with  WW  genotype.

Serum uric acid distribution according to SLC22A12 W258X genotype in a cross-sectional study of a general Japanese population