Cystinuria is an inherited
metabolic disease characterized by an abnormal urinary excretion of
cystine and
dibasic amino acids. Formation of
renal calculi,
recurrent infections and
renal failure are the main complications of this disease. The SLC3A1 gene, which codes for a dibasic
amino acid transporter protein, is involved in the pathogenesis of
cystinuria. We investigated the possible association between molecular variants (M467T, E483X, T216 M and 114 C-->A) within the SLC3A1 gene and some phenotypical traits in a Spanish area. The study population consisted of 45
cystinuria patients, 42
cystinuria relatives and 81 healthy control subjects. Only the M467T mutation was found in chromosomes of
cystinuria patients and relatives. However, the 114 C-->A polymorphism was detected in
cystinuria patients, in relatives and in control subjects but with different prevalences. Moreover, a statistically significant association between this polymorphism and urinary
amino acid levels was found in
cystinuria patients (P<0.05). Subjects with the C/C genotype showed significantly higher urinary levels of
cystine,
arginine and their sum as compared with carriers of the A allele (P<0.05). When multiple linear regression analysis was performed in
cystinuria patients, the 114 C-->A polymorphism remained significantly associated (P=0.047) with
cystine levels even after controlling for age, gender and the M467T mutation. Furthermore, we also found a statistically significant interaction term (P=0.028) between M467T and 114 C-->A in determining urinary
cystine levels. According to our results, the 114 C-->A polymorphism might be a marker of a functional variant in the SLC3A1 gene or in other genes related to urinary
amino acid excretion in
cystinuria patients.