To evaluate the association of fetuin-A polymorphisms with calcium oxalate nephrolithiasis. Fetuin-A is a circulating calcium-regulatory glycoprotein that inhibits extraosseous calcification.Fetuin-A c.742C > T and c.766C > G polymorphisms were investigated in 103 patients with calcium oxalate nephrolithiasis and 73 age- and gender-matched healthy volunteers, using polymerase chain reaction-restriction fragment length polymorphism techniques. Additionally, we compared serum fetuin-A levels in the 2 groups.A statistically significant difference was observed between the control and patient groups (chi(2) test, P = .003) for the genotype of fetuin-A c.766C > G polymorphism. The odds ratio (95% confidence interval) for the CG genotype in those at risk of stone disease was 4.2 (1.73-10.28). The frequency distribution for fetuin-A c.742C > T polymorphism was not statistically different in stone patients and controls (P = .77). Serum mean fetuin-A concentration was significantly lower in the patients (710.38 +/- 156.42 microg/mL) than in the controls (810.89 +/- 173.43 microg/mL, P = .0001). In the patient group (but not in the control group), subjects carrying fetuin-A genotype 1 had significantly higher serum fetuin-A concentrations than the group carrying fetuin-A genotype 2-1 (P = .001).These results reveal that the patients with fetuin-A c.766C > G gene polymorphism may be at higher risk for renal calcium oxalate stone formation.