Functional characterization of human xanthine oxidase allelic variants.

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Xanthine oxidase (XO ) catalyzes the oxidation of endogenous and exogenous purines and pyrimidines . In this study , we speculated that individual variations in XO activity are caused by genetic variations in the XO gene .To investigate the genetic variations in XO in 96 Japanese participants , denaturing high -performance liquid chromatography was used . To assess the effects of these variations on enzymatic activity , wild-type XO and 21 types of variant XO--including those in the database and those just discovered--were transiently expressed in COS -7 cells .T hree nonsynonymous single nucleotide polymorphisms , including 514 G >A (Gly 172 A rg ), 3326 A >C (Asp 1109 Thr ), and 3662 A >G (His 1221 A rg ) were identified in Japanese participants . Functional characterization of 21 XO variants showed a deficiency in enzyme activity in two variants (Arg 149 C ys and Thr 910 L ys ); low activity (intrinsic clearance , CLint : 22 -69 % compared with the wild-type ) in six variants (Pro 555 S er , Arg 607 G ln , Thr 623 I le , Asn 909 L ys , Pro 1150 A rg , and Cys 1318 T yr ); and high activity (CLint : approximately two-fold higher than that in the wild-type ) in two variants (Ile 703 V al and His 1221 Arg ).These results suggest that several single nucleotide polymorphisms in the XO gene are involved in individual variations in XO activity . In addition , such findings will be useful to identify xanthinuria patients .