Association between M467T and 114 C -> A variants within the SLC3A1 gene and some phenotypical traits in cystinuria patients from Spain

Cystinuria is an inherited metabolic disease characterized by an abnormal u rinary excretion of cystine and dibasic amino acids. Formation of renal cal culi, recurrent infections and renal failure are the main complications of this disease. The SLC3A1 gene, which codes for a dibasic amino acid transpo rter protein, is involved in the pathogenesis of cystinuria. We investigate d the possible association between molecular variants (M467T, E483X. T216 M and 114 C-->A) within the SLC3A1 gene and some phenotypical traits in a Sp anish area. The study population consisted of 45 cystinuria patients, 42 cy stinuria relatives and 81 healthy control subjects. Only the M467T mutation was found in chromosomes of cystinuria patients and relatives. However, th e 114 C-->A polymorphism was detected in cystinuria patients, in relatives and in control subjects but with different prevalences. Moreover, a statist ically significant association between this polymorphism and urinary amino acid levels was found in cystinuria patients (P<0.05). Subjects with the C/ C gene; type showed significantly higher urinary levels of cystine, arginin e and their sum as compared with carriers of the A allele (P<0.05). When mu ltiple linear regression analysis was performed in cystinuria patients, the 114 C-->A polymorphism remained significantly associated (P=0.047) with cy stine levels even after controlling fur 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.